Pyloromyotomy is a technique for relieving infantile hypertrophic pyloric stenosis and is performed almost safely without severe complications during long-term outcomes. To the best of our knowledge, this is the first reported case of pancreatic cancer arising from the pancreatic parenchyma embedded within the pyloric ring after neonatal pyloromyotomy. A 39-year-old woman with a history of infantile hypertrophic pyloric stenosis underwent a pyloromyotomy during the neonatal period and presented with progressive nausea and vomiting. Imaging studies suggested the presence of ectopic pancreatic or gastric cancer invading the pancreas. After laparotomy, tumor invasion of the pancreatic head was identified; therefore, pancreaticoduodenectomy was performed. Pathological examination confirmed pancreatic cancer arising from the pancreatic parenchyma embedded within the duodenal and pyloric muscle layers. The patient completed 6 months of adjuvant chemotherapy with oral S-1. Peritoneal dissemination was observed 23 months postoperatively. Abnormal embedding of the pancreatic head in the walls of the duodenum and pyloric ring was considered to be related to neonatal pyloromyotomy. This alteration requires careful preoperative evaluation and flexible surgical planning to achieve curative resection of atypical presentations of gastrointestinal malignancies. The cancer in the present case may be associated with long-term anatomical alterations following neonatal pyloromyotomy, although a direct causal relationship cannot be established.

BACKGROUND:Myxoid stroma in the tumor stroma has been suggested to play a key role in cancer progression; however, its underlying mechanisms remain unclear. This study aimed to examine the relationship between myxoid stroma, identified in hematoxylin and eosin (HE)-stained tissue, and tumor-infiltrating lymphocytes (TILs), assessed through immunohistochemical staining. Automated image analysis was employed to evaluate these features, and their clinical significance in esophageal squamous cell carcinoma (ESCC) was investigated. METHODS:A total of 139 ESCC patients who underwent esophagectomy were included. From each patient, three serial sections from paraffin blocks were prepared and stained with CD3, HE, and CD8, respectively. An algorithm for identifying myxoid stroma was applied to HE slides, and the resulting data were mapped onto the corresponding CD3 and CD8 slides to analyze the spatial relationship between these pathological findings. RESULTS:The myxoid-high group, comprising 76 cases, had significantly deeper tumor depth compared to the myxoid-low group, which included 63 cases (p < 0.05). CD3+ cell density was significantly lower in the myxoid-high group compared to the myxoid-low group (p < 0.01). Within the myxoid stroma regions, CD3+ cell density was significantly lower than in regions outside the stroma (p < 0.01). The mean distance of all CD3+ cells from the edges of the myxoid stroma was significantly greater than that from the tumor margin (p < 0.01). Similar results were observed for CD8+ cells. CONCLUSIONS:In conclusion, this study demonstrated that myxoid stroma in the invasive front of ESCC is closely associated with the density of CD3+ and CD8+ positive lymphocytes.

Tumor cell nuclear size (NS) indicates malignant potential in breast cancer; however, its clinical significance in esophageal squamous cell carcinoma (ESCC) is unknown. Artificial intelligence (AI) can quantitatively evaluate histopathological findings. The aim was to measure NS in ESCC using AI and elucidate its clinical significance. We investigated the relationship between NS assessed by AI and prognosis in 138 patients with ESCC who underwent curative esophagectomy. Hematoxylin and eosin-stained slides from the deepest tumor sections were digitized. Using HALO-AI DenseNet v2, we created a deep-learning classifier that identified tumor cells with an NS area >20 mm(2). Median NS was 40.14 mm(2), which was used to divide patients into NS-high and NS-low groups (n = 69 per group). Five-year overall survival (OS) and relapse-free survival rates were significantly lower in the NS-high group (43.2% and 39.6%) than in the NS-low group (67.7% and 49.6%). Multivariate analysis showed that greater tumor depth and NS-high status (hazard ratio: 1.79; P = .032) were independent risk factors for OS. In 77 cases with neoadjuvant chemotherapy, increased tumor depth and NS-high status (hazard ratio: 1.99; P =.048) were independent prognostic factors for unfavorable OS. Compared with the NS-low group, the NS-high group had significantly higher anisokaryosis, higher Ki-67 expression as calculated by AI analysis of immunostaining, and higher NS heterogeneity as examined by equidividing the tumors into square tiles. In conclusion, NS assessed by AI is a simple and useful prognostic factor for ESCC. (c) 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

INTRODUCTION:Esophageal squamous cell carcinoma is an aggressive malignancy often diagnosed at an advanced stage. Immune checkpoint inhibitors (ICIs), such as pembrolizumab, have shown promising outcomes for improving survival. Although rare, immune-related adverse events (irAEs) associated with ICI therapy, such as pneumatosis intestinalis (PI) and portal venous gas (PVG), can be fatal. CASE PRESENTATION:A 60-year-old man with unresectable advanced esophageal squamous cell carcinoma received cisplatin, 5-fluorouracil (FP), and pembrolizumab. Three days after treatment initiation, the patient experienced abdominal pain and hypotension. Imaging revealed extensive PI and PVG, with no signs of bowel ischemia. Emergency laparotomy confirmed PI involving the entire length of the small intestine, with no visible perforations. Symptoms resolved with conservative management. After benefits and potential adverse events of the current chemotherapy regimen were explained, the patient chose to continue pembrolizumab-based chemotherapy. In the second and third courses, the doses of cisplatin and 5-FU were reduced to 75% (cisplatin 60 mg/m2, 5-FU 600 mg/m2), while the dose of pembrolizumab was maintained (200 mg). No major adverse events occurred, and follow-up CT scans showed shrinkage of the primary lesion, and PI did not recur during this period. However, 26 days after the 3rd treatment course, the patient developed sudden-onset abdominal pain, shock, more severe PI, and PVG. Despite receiving intensive care, the patient died the following day. Autopsy revealed diffuse intestinal erosion with a CD8-positive lymphocytic infiltration and histologically confirmed pneumatosis intestinalis extensively involving the small intestine and colon. CONCLUSIONS:The patient experienced two episodes of PI and PVG with distinct clinical courses. Although the exact cause of the first episode remains unclear, the fatal recurrence suggests that rechallenging with suspected causative agents carries a significant risk, even after dose reduction. While ICI-based chemotherapy for esophageal cancer was highly effective, this case highlights the importance of continuously reassessing the risk-benefit balance during treatment. Discontinuation of ICIs should be considered when serious irAE are suspected.

Postoperative infectious complications (PICs) are major adverse events following gastrectomy for gastric cancer. The present study investigated whether preoperative programmed cell death 1 (PD-1)+CD4+ lymphocytes reflect immunological and physical frailty and predict PICs. A total of 85 patients who underwent gastrectomy for gastric cancer were retrospectively enrolled. Blood samples were collected preoperatively, and PD-1+CD4+ cells were analyzed using flow cytometry. Patients were divided into PD-1high (N=43) and PD-1low (N=42) groups based on the median value of preoperative PD-1+CD4+/CD4+ cells (cutoff, 22.3%). Preoperative immune-inflammatory markers and nutritional indices included the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutrition index (PNI) and controlling nutritional status (CONUT) score. Physical vulnerability was assessed using the fall risk assessment score (FRAS) and Charlson comorbidity index (CCI). The PD-1high group was older than the PD-1low group, with no significant differences in sex, comorbidities, or surgical and pathological factors. The PD-1high group had a significantly higher incidence of the PICs (42 vs. 19%; P<0.05). In addition, the PD-1high group exhibited higher C-reactive protein levels, and lower total lymphocyte counts and albumin levels compared with the PD-1low group (P<0.05, respectively). The two groups had significant differences in preoperative NLR, CAR, PNI, CONUT score and FRAS. Notably, there were significant associations between PD-1+CD4+/CD4+ cells and NLR, PLR, CONUT score, PNI, FRAS and CCI (all P<0.05). Preoperative PD-1+CD4+/CD4+ cells were significantly associated with increased PIC risk and markers of immunological and physical frailty. This biomarker may be useful for identifying vulnerable patients requiring tailored perioperative care.

INTRODUCTION:Immune checkpoint inhibitors (ICIs) have extended survival in various cancers, especially when combined with chemotherapy. This effect is thought to involve tumor-specific antigen release and T cell reactivation. The "abscopal effect," where radiation leads to tumor shrinkage at distant sites, may also be enhanced by ICIs, although this is not fully understood. Photodynamic therapy (PDT), a localized treatment, has shown potential for inducing abscopal effects, but no studies have investigated this in metronomic PDT (mPDT), which uses low fluence rates over extended periods. This study aimed to evaluate if mPDT exerts the abscopal effect and whether the addition of ICIs can enhance this effect. METHODS:Colon-26 tumor-bearing mice were treated with conventional (cPDT) or mPDT, with or without anti-PD-L1 antibodies. Tumor growth in target and nontarget lesions was measured, and immune cell infiltration was analyzed by flow cytometry. RESULTS:When combined with anti-PD-L1, cPDT significantly reduced tumor size in nontarget lesions and increased the infiltration of CD4+, CD8+, and CD3+ cells in these areas. In contrast, mPDT did not elicit a comparable antitumor response or promote CD4+, CD8+, and CD3+ cell infiltration in nontarget lesions. CONCLUSIONS:While cPDT combined with ICIs successfully reduced tumor size in nontarget lesion, mPDT did not, suggesting a limited capacity to induce systemic immune responses. Further research is needed to optimize mPDT for systemic cancer therapy.

Prompt diagnosis of strangulated bowel obstruction (SBO) is critical because delayed recognition can lead to life-threatening complications. This study assessed whether the intestinal-to-liver CT attenuation value ratio—a comparison of ischemic bowel-wall enhancement to liver enhancement—can predict the need for intestinal resection in SBO patients. We retrospectively analyzed 52 patients who underwent emergency surgery for suspected SBO from 2014 to 2021. Of these, 35 required intestinal resection due to irreversible ischemia (resection group), while 17 did not (no-resection group). Preoperative clinical and imaging findings were compared between groups. The resection group had a longer time from onset to surgery (p = 0.034) and higher leukocyte counts (p = 0.037). CT values of the poorly enhanced intestinal wall and the intestinal-to-liver attenuation ratio were significantly lower in the resection group (p < 0.0001). Multivariate analysis identified time to surgery (OR 5.08; 95

INTRODUCTION:Laparoscopic and robotic gastrectomies have become standard procedures for the treatment of gastric cancer. Among the reconstruction methods used following distal gastrectomy, the Billroth-I technique is often preferred owing to its low complication rates. Delta-shaped anastomosis, a method that eliminates the need for a mini-laparotomy, represents a significant advancement in minimally invasive surgeries. In this report, we aim to present a novel technique using bidirectional barbed sutures for temporary closure of the entry hole during delta-shaped anastomosis in laparoscopic and robotic gastrectomies. MATERIALS AND SURGICAL TECHNIQUE:The entry hole was closed using a bidirectional barbed suture, starting centrally to prevent overlapping of the gastric and duodenal staple lines. The suture length was meticulously adjusted to align with the stapler dimensions. All the procedures were successfully completed without any complications in both laparoscopic and robotic gastrectomies. Bidirectional barbed sutures enabled precise tissue alignment and prevented slippage, thereby facilitating secure, full-thickness closure of the entry hole while minimizing the risk of incomplete stapler firing. CONCLUSION:Bidirectional barbed sutures offer a safe and feasible alternative option for the temporary closure of the entry hole during a stapled anastomotic technique in robotic and laparoscopic gastrectomies.

Introduction: We investigated the drug resistance status of Pseudomonas aeruginosa (P. aeruginosa) focusing on its isolation sites and types of diseases. Materials and methods : A microbiological laboratory database was searched to identify all clinical cultures positive for P. aeruginosa. Clinicopathologic features and susceptibility of P. aeruginosa to any antibiotics were evaluated in patients admitted to the division of upper (Upper- GI group) or lower gastrointestinal surgery (Lower- GI group). In addition, we investigated the susceptibility of P. aeruginosa to any antibiotics based on the isolation site. Results: P. aeruginosa was frequently detected in the sputum and urine of the Upper- GI and Lower- GI groups, respectively. Among P. aeruginosa isolates from drain discharge, a significantly higher rate of resistance to imipenem, amikacin, and ciprofloxacin was observed; among P. aeruginosa isolates from wounds, a substantially higher proportion had resistance to imipenem and cefozopran in the Upper- GI group. However, there was no difference between the two groups in the drug resistance of P. aeruginosa isolated from urine, sputum, blood, and ascites. P. aeruginosa isolated from sputum showed more resistance to imipenem and ciprofloxacin than those isolated from other sites. Conclusion : There were significant differences in the drug resistance ofP. aeruginosa based on the isolation sites and types of diseases.

PURPOSE:We investigated the relationship between the resected stomach measurements, the incidence of delayed gastric emptying (DGE), and food residue 1 year after surgery in patients who underwent laparoscopic pylorus-preserving gastrectomy (PPG). MATERIALS AND METHODS:The DGE group included 10 patients fasting due to nausea, vomiting, abdominal distension, or remnant stomach distension on radiographs; the control group included 36 patients without these symptoms. We compared the size and length of lesser and greater curvatures of the resected stomach and endoscopic findings after 1 year. RESULTS:No significant differences were observed between groups in terms of sex, body mass index, gross type, histology, tumor progression, number of dissected lymph nodes, operating time, or blood loss. The DGE group was older, had a longer postoperative stay, and showed a smaller size and shorter greater curvature of the resected stomach than the control group (p < 0.01 for all). No difference was observed in the length of the lesser curvature of the resected stomach. In addition, there were no disparities in residual food, degree and extent of gastritis, or bile reflux 1 year after gastrectomy. CONCLUSIONS:Measurements of the resected stomach suggest that preventing DGE may be achievable by removing a larger area of the greater curvature and/or stomach during laparoscopic PPG. This implies potential surgical strategy improvements for better outcomes. Further multicenter trials are needed to validate and refine techniques.

Background: Serum and tissue human epidermal growth factor receptor 2 (HER2) levels were evaluated in resected esophageal squamous cell carcinoma (SCC) specimens to assess the relationship between HER2 expression and long-term prognosis. Methods: We included 95 patients who underwent esophagectomy for esophageal SCC. The serum HER2-extracellular domain (sHER2-ECD) levels were measured using an ELISA kit. A time-dependent receiver operating characteristics curve for censored survival outcomes was constructed to estimate the optimal cut-off value of sHER2-ECD (set at 4211 pg/mL). Immunohistochemical (IHC) staining was performed for HER2, and specimens were classified based on low (0 or 1 + ) or high HER2-IHC expression (2 + or 3 + ). Results: Patients with low sHER2-ECD levels showed poorly differentiated tumors, nodal involvement, and larger tumor size more frequently compared to patients with high sHER2-ECD levels. There were no differences in clinicopathological features based on HER2-IHC expression. Between patients with high and low HER2-IHC expression, the former group showed significantly higher sHER2-ECD levels. Patients with high sHER2-ECD levels had significantly favorable relapse-free survival (RFS) and overall survival (OS) compared to those with low sHER2-ECD levels. Conversely, patients with high HER2-IHC expression had significantly poorer RFS than did patients with low HER2-IHC expression, although no difference was observed in OS. Additionally, patients with high sHER2-ECD levels and low HER2-IHC expression had the highest OS and RFS among the patients studied. Conclusions: The correlation among sHER2-ECD levels, HER2-IHC expression, and prognosis was demonstrated. Prospective studies are required to validate the impact of serum and tissue HER2 expression in esophageal SCC prognosis. (C) 2021 Elsevier Inc. All rights reserved.

It has been reported that immuno-inflammatory and nutritional parameters are associated with long-term survival in various malignancies. However, little is known regarding the associations between alterations of these parameters during neoadjuvant chemotherapy (NAC) and the response to NAC in patients with esophageal cancer. The present study examined the clinical significance of alterations in these parameters during NAC in terms of the response to NAC and the long-term outcomes in patients with esophageal cancer. Various systemic immuno-inflammatory and nutritional measures including the systemic neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP)-to-albumin ratio (CAR) and psoas muscle index (PMI) were examined before and after NAC. Statistical analyses were performed to determine the significance of immuno-inflammatory and nutritional parameters prior to NAC and alterations during NAC regarding the response to NAC and long-term outcomes. The NLR, PMI, neutrophil count and platelet count declined significantly following NAC, whereas no alterations in PLR, CAR, lymphocyte counts, CRP levels and albumin concentration were observed. The decreases in NLR and neutrophil counts following NAC were strongly associated with a favorable overall survival (P=0.006). In conclusion, decreases in NLR and neutrophil counts following NAC were clinically significant predictors of the response to NAC and of survival in esophageal cancer, respectively.

Background: Increasing evidence has demonstrated that postoperative infectious complications (PICs) after digestive surgery are significantly associated with negative long-term outcomes; however, precise mechanisms of how PICs affect the poor long-term survival remain unclear. Here, we focused on the hepatocyte growth factor (HGF)/c-Met signaling pathway as one of those mechanisms.Methods:In the clinical setting, serum HGF levels were measured in the patients with sepsis and those with PICs after undergoing esophagectomy. Using a liver metastasis mouse model with cecal ligation and puncture (CLP), expressions of HGF and the roles of the HGF/c-Met pathway in the progression of tumor cells were examined.Results:Serum HGF levels were very high in the patients with intra-abdominal infection on postoperative days (PODs) 1, 3, and 5; similarly, compared to the patients without PICs, those with PICs had significantly higher serum HGF levels on 1, 3, and 5 days after esophagectomy. The patients with PICs showed poorer overall survival than those without PICs, and the patients with high serum HGF levels on POD 3 showed poorer prognosis than those with low HGF levels. Similarly, at 24 and 72 h after operation, serum levels of HGF in CLP mice were significantly higher than those in sham-operated mice. Intraperitoneal injection of mouse recombinant HGF significantly promoted liver metastases in sham-operated mice on 14 days after surgery. Knocking down c-Met expression on NL17 tumor cells by RNAi technology significantly inhibited the promotion of CLP-induced liver metastases.Conclusions:Infections after surgery increased serum HGF levels in the clinical as well as experimental settings. Induction of high serum HGF levels by CLP promoted liver metastases in a murine liver metastasis model, suggesting the involvement of the HGF/c-Met signaling pathway in tumor promotion mechanisms. Thus, targeting the HGF/c-Met signaling pathway may be a promising approach for malignant tumors, particularly in the patients with PICs.

Background: The aim of this study was to evaluate the association between the expression of programmed death ligand-1 (PD-L1) and clinical outcomes in patients with surgically resected esophageal squamous cell carcinoma (ESCC). Materials and methods: We included 76 patients with primary ESCC who underwent surgical resection between January 2009 and December 2014 at National Defense Medical College Hospital. Using the tumor tissues, we evaluated PD-L1 expression in tumor cells and stromal reactive lymphocytes via immunohistochemistry. Furthermore, the relationship between PD-L1 expression and the clinicopathological status of patients with ESCC was investigated. Results: PD-L1 expression in tumor cells was detected in 39.5% of the patients. In addition, 51.3% of the patients had PD-L1-positive stromal reactive lymphocytes and exhibited significantly longer overall survival than those with lack of PD-L1 expression in stromal reactive lymphocytes (median survival time, 56.0 versus 27.3 mo; log-rank test, P = 0.04). Patients with lack of PD-L1 expression in both tumor cells and stromal reactive lymphocytes showed worse overall survival than those with the PD-L1-positive expression in tumor cells and/or stromal reactive lymphocytes (P = 0.02). Conclusions: PD-L1-positive expression in stromal reactive lymphocytes, rather than in tumor cells, is associated with a longer survival in patients with ESCC. (C) 2020 Published by Elsevier Inc.

BACKGROUND/AIM:Local and systemic inflammations are associated with negative long-term outcomes; however, their precise mechanism of action remains unclear. We previously demonstrated that hepatocyte growth factor (HGF)/c-Met signaling contributed to the enhancement of liver metastasis associated with peritonitis model. The aim of this study is to investigate the effect of local inflammation on the development of lung metastasis.MATERIALS AND METHODS:NL-17 cells were injected into BALB/c mice via the tail vein to produce a high potential model for lung metastasis. After injection of NL-17 cells, lipopolysaccharide (LPS) and live Pseudomonas aeruginosa, and phosphate-buffered saline were administered intratracheally to induce acute lung injury (ALI) and pneumonia, respectively.RESULTS:In both ALI and pneumonia mice, lung metastasis was significantly promoted compared to control mice. Concentrations of Interleukin-6, tumor necrosis factor-α, and HGF in the bronchoalveolar lavage fluid were significantly higher in ALI and pneumonia mice than in control mice. Neither administration of recombinant mouse HGF nor c-Met knockdown in NL-17 cells influenced the magnitude of lung metastasis. Yet stimulation with LPS increased the expression of α2 integrin, vascular cell-adhesion protein-1, and intercellular adhesion molecule-1 (ICAM-1) in the lung. Invasive activity of NL-17 cells was significantly up-regulated by LPS, but was suppressed by anti-ICAM-1 antibody. While LPS-stimulated NL-17 cells showed significantly promoted lung metastasis, E-selectin expression in the lungs of mice with ALI or pneumonia was significantly enhanced compared with control mice.CONCLUSION:Up-regulation of adhesion molecules, but not HGF/c-Met signaling, may contribute to the lung metastasis enhanced by local infection/inflammation.

OBJECTIVES:Our goal was to "reverse translate" the human response to surgical sepsis into the mouse by modifying a widely adopted murine intra-abdominal sepsis model to engender a phenotype that conforms to current sepsis definitions and follows the most recent expert recommendations for animal preclinical sepsis research. Furthermore, we aimed to create a model that allows the study of aging on the long-term host response to sepsis.DESIGN:Experimental study.SETTING:Research laboratory.SUBJECTS:Young (3-5 mo) and old (18-22 mo) C57BL/6j mice.INTERVENTIONS:Mice received no intervention or were subjected to polymicrobial sepsis with cecal ligation and puncture followed by fluid resuscitation, analgesia, and antibiotics. Subsets of mice received daily chronic stress after cecal ligation and puncture for 14 days. Additionally, modifications were made to ensure that "Minimum Quality Threshold in Pre-Clinical Sepsis Studies" recommendations were followed.MEASUREMENTS AND MAIN RESULTS:Old mice exhibited increased mortality following both cecal ligation and puncture and cecal ligation and puncture + daily chronic stress when compared with young mice. Old mice developed marked hepatic and/or renal dysfunction, supported by elevations in plasma aspartate aminotransferase, blood urea nitrogen, and creatinine, 8 and 24 hours following cecal ligation and puncture. Similar to human sepsis, old mice demonstrated low-grade systemic inflammation 14 days after cecal ligation and puncture + daily chronic stress and evidence of immunosuppression, as determined by increased serum concentrations of multiple pro- and anti-inflammatory cytokines and chemokines when compared with young septic mice. In addition, old mice demonstrated expansion of myeloid-derived suppressor cell populations and sustained weight loss following cecal ligation and puncture + daily chronic stress, again similar to the human condition.CONCLUSIONS:The results indicate that this murine cecal ligation and puncture + daily chronic stress model of surgical sepsis in old mice adhered to current Minimum Quality Threshold in Pre-Clinical Sepsis Studies guidelines and met Sepsis-3 criteria. In addition, it effectively created a state of persistent inflammation, immunosuppression, and weight loss, thought to be a key aspect of chronic sepsis pathobiology and increasingly more prevalent after human sepsis.