Preoperative factors associated with lateral lymph node metastasis in lower rectal cancer and the evaluation of the middle rectal artery.

PURPOSE: This study aimed to identify cases in which lateral lymph node (LLN) dissection (LLND) can be excluded by clarifying preoperative factors, including an evaluation of the middle rectal artery (MRA), associated with LLN metastasis. METHODS: Fifty-five consecutive patients who underwent preoperative positron emission tomography-computed tomography (PET/CT) and total mesorectal excision with LLND for rectal cancer were included. We retrospectively investigated the preoperative clinical factors associated with pathological LLN (pLLN) metastasis. We analyzed the regions of pLLN metastasis using MRA. RESULTS: pLLN metastasis occurred in 13 (23.6%) patients. According to a multivariate analysis, clinical LLN (cLLN) metastasis based on short-axis size and LLN status based on PET/CT were independent preoperative factors of pLLN metastasis. The negative predictive value (NPV) was high (97.1%) in patients evaluated as negative based on PET/CT and cLLN short-axis size. MRA was detected in 24 patients (43.6%) using contrast-enhanced CT, and there was a significant relationship between pLLN metastasis and the presence of MRA. pLLN metastasis in the internal iliac region but not in the obturator region was significantly correlated with the presence of MRA. CONCLUSION: Combined cLLN metastasis based on short-axis size and PET/CT showed a higher NPV, suggesting this to be a useful method for identifying cases in which LLND can be excluded.

Usefulness of the preoperative inflammation-based prognostic score and the ratio of visceral fat area to psoas muscle area on predicting survival for surgically resected adenocarcinoma of the esophagogastric junction.

BACKGROUND: Sarcopenic obesity is associated with gastrointestinal cancer prognosis through systemic inflammation. However, in patients with adenocarcinoma of the esophagogastric junction (AEG), the relationship between the inflammation-based prognostic score (IBPS), muscle loss, visceral fat mass, and prognosis has not been sufficiently evaluated. We investigated the prognostic value of the preoperative IBPS and the visceral fat area ratio to the psoas muscle area (V/P ratio) in patients with AEG undergoing surgery. METHODS: We retrospectively analyzed 92 patients with AEG who underwent surgery. The prognostic value of the preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio, systemic inflammation response index, C-reactive protein-to-albumin ratio, prognostic nutritional index, modified Glasgow Prognostic Score, and V/P ratio at the third lumbar vertebra was investigated using univariate and multivariate survival analyses. RESULTS: Multivariate analysis revealed that a high pathological stage (p = 0.0065), high PLR (p = 0.0421), and low V/P ratio (p = 0.0053) were independent prognostic factors for poor overall survival (OS). When restricted to patients with body mass index (BMI) ≥ 25 kg/m2, a high V/P ratio was a poor prognostic factor (p = 0.0463) for OS. Conversely, when restricted to patients with BMI < 25 kg/m2, a low V/P ratio was a poor prognostic factor (p = 0.0021) for OS. CONCLUSIONS: Both PLR and V/P ratios may be useful prognostic biomarkers in surgical cases of AEG. V/P ratio and BMI may provide an accurate understanding of the muscle and fat mass's precise nature and may help predict AEG prognosis.

Efficacy of thoracic endovascular aortic repair for aorto-esophageal fistula due to esophageal cancer: a systematic review and meta-analysis.

Aorto-esophageal fistula (AEF) due to esophageal cancer (EC) is a life-threatening condition characterized by sudden hemorrhage, which often causes sudden death. To evaluate the efficacy and safety of thoracic endovascular aortic repair (TEVAR) for AEF due to EC, we performed a systematic review and meta-analysis. We searched the MEDLINE (PubMed) databases, the Cochrane Library databases, Ichushi-Web (the databases of the Japan Medical Abstract Society), and CiNii (Academic information search service of the National Institute of Information from Japan) from January 2000 to November 2023 for articles about TEVAR for an emergent aortic hemorrhage (salvage TEVAR [S-TEVAR]), and the prophylactic procedure (P-TEVAR). Six studies (140 cases) were eligible for meta-analysis. The 90-day mortality of S-TEVAR and P-TEVAR was 40% (95% CI 23-60, I2 = 36%) and 8% (95% CI 3-17, I2 = 0%), respectively. Post-S-TEVAR hemorrhagic and infectious complications were 17% (95% CI 3-57, I2 = 71%) and 20% (95% CI 5-57, I2 = 66%), respectively. Post-P-TEVAR hemorrhagic and infectious complications were 2% (95% CI 0-10, I2 = 0%) and 3% (95% CI 1-12, I2 = 0%), respectively. TEVAR for AEF due to EC may be a useful therapeutic option to manage or prevent hemorrhagic oncological emergencies.

Infiltration of Gastric Cancer Stroma by Tumor-Infiltrating Lymphocytes Correlates with Mechanistic Target of Rapamycin Signaling.

INTRODUCTION: We investigated whether the infiltration of tumor-infiltrating lymphocytes (TILs) in gastric cancer (GC), as evaluated by hematoxylin and eosin (H&E) staining, could be a prognostic marker. We also explored on the relationship between TILs and mechanistic target of rapamycin (mTOR) and how it regulates immune effector responses in GC. METHODS: A total of 183 patients with available data on TIL were included. TIL infiltration was evaluated using H&E staining. We also conducted immunohistochemistry to determine mTOR expression. RESULTS: Positive TIL infiltration was defined as TILs ≥20%. There were 72 (39.3%) and 111 (60.7%) positive and negative cases, respectively. TILs positivity significantly correlated with both absence of lymph node metastasis (p = 0.037) and negative p-mTOR expression (p = 0.040). TIL infiltration correlated with a significantly better overall (p = 0.046) and disease-free (p = 0.020) survival. CONCLUSION: mTOR possibly suppresses TIL infiltration in GC. H&E staining is an effective tool for evaluating the immune status of GC patients. H&E staining may be used in clinical practice to monitor treatment response in GC.

Retroperitoneal urothelial carcinoma arising after bladder diverticulectomy: a case report.

BACKGROUND: Urothelial carcinoma arises from the inner urothelial membrane of the renal pelvis, ureter, and bladder and often causes macrohematuria. Here, we report a rare case in which the patient developed non-symptomatic urothelial carcinoma anatomically outside the bladder wall 17 years after bladder diverticulectomy. CASE PRESENTATION: An 82-year-old male patient previously underwent gastrectomy for stomach cancer and partial hepatectomy for intrahepatic cholangiocarcinoma. Follow-up computed tomography revealed a tumor in the retroperitoneal space, where a bladder diverticulum was removed 17 years earlier. Multiparametric magnetic resonance imaging suggested that the tumor was malignant with rectal invasion. Subsequent computed tomography-guided percutaneous biopsy revealed that the tumor was urothelial carcinoma. The patient underwent two courses of neoadjuvant chemotherapy followed by pelvic exenteration with pelvic lymph node dissection. He is currently receiving adjuvant therapy with an immune checkpoint inhibitor and has had no recurrence for 3 months. CONCLUSIONS: Multiparametric magnetic resonance imaging is a helpful tool for predicting both tumor malignancy and invasion before a pathologically confirmed diagnosis. Although this case is rare, urologists should be aware of the occurrence of urothelial carcinoma after bladder diverticulectomy in cases of incomplete resection of the diverticulum.

Field carcinogenesis and biological significance of the potential of the bystander effect: carcinogenesis, therapeutic response, and tissue regeneration.

The "bystander effect" is a transmission phenomenon mediating communication from target to non-target cells, as well as cell-to-cell interactions between neighboring and distantly located cells. In this narrative review, we describe the fundamental and clinical significance of the bystander effect with respect to cell-to-cell interactions in carcinogenesis, therapeutic response, and tissue regeneration. In carcinogenesis, the bystander effect mediates communications between tumor microenvironments and non-malignant epithelial cells and has been suggested to impact heterogeneous tumorigenic cells in tumors and cancerized fields. In therapeutic response, the bystander effect mediates communications between drug-sensitive and drug-resistant cells and may transmit both drug efficacy and resistance. Therefore, control of therapeutic response transmission via the bystander effect might offer a promising future cancer treatment. Finally, in tissue regeneration, circulating cells and stromal cells may differentiate into various cells for the purpose of tissue regeneration under direction of the bystander effect arising from surrounding cells in a defective space. We hope that the findings we present will promote the development of innovative cancer therapies and tissue regeneration methodologies from the viewpoint of cell-to-cell interactions through the bystander effect.

Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity.

Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer antigen. We retrospectively recruited 198 patients with gastric cancer who underwent surgery. The presence of lipopolysaccharides was determined using immunohistochemical staining, with the intensity score indicating positivity. The relationship between lipopolysaccharides and CD8, PD-L1, TGFBI (a representative downstream gene of TGF-ß signaling), wnt3a, and E-cadherin (epithelial-mesenchymal transition marker) was also investigated. Thereafter, we identified 20 patients with advanced gastric cancer receiving nivolumab and investigated the relationship between lipopolysaccharides and nivolumab sensitivity. After staining for lipopolysaccharides in the nucleus of cancer cells, 150 negative (75.8%) and 48 positive cases (24.2%) were found. The lipopolysaccharide-positive group showed increased cancer stromal TGFBI expression (p < 0.0001) and PD-L1 expression in cancer cells (p = 0.0029). Lipopolysaccharide positivity was significantly correlated with increased wnt3a signaling (p = 0.0028) and decreased E-cadherin expression (p = 0.0055); however, no significant correlation was found between lipopolysaccharide expression and overall survival rate (p = 0.71). In contrast, high TGFBI expression in the presence of LPS was associated with a worse prognosis than that in the absence of LPS (p = 0.049). Among cases receiving nivolumab, the lipopolysaccharide-negative and -positive groups had disease control rates of 66.7% and 11.8%, respectively (p = 0.088). Lipopolysaccharide positivity was associated with wnt3a, TGF-ß signaling, and epithelial-mesenchymal transition and was considered to tend to promote therapeutic resistance to nivolumab.

Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy.

The mammalian target of rapamycin (mTOR) is often activated in several cancers. We focused on two mTOR regulatory mechanisms: oxaliplatin-induced mTOR signaling and L-type amino acid transporter 1 (LAT1)-induced mTOR activation. High LAT1 expression in several cancers is associated with mTOR activation and resistance to chemotherapy. However, the significance of LAT1 has not yet been elucidated in colorectal cancer (CRC) patients treated with post-operative adjuvant chemotherapy. Immunohistochemistry was conducted to examine the significance of membrane LAT1 expression in 98 CRC patients who received adjuvant chemotherapy, including oxaliplatin. In vitro analysis was performed using CRC cell lines to determine the effects of LAT1 suppression on proliferation, oxaliplatin sensitivity, and mTOR signaling. LAT1 expression was associated with cancer aggressiveness and poor prognosis in 98 CRC patients treated with adjuvant chemotherapy. We found that positive LAT1 expression correlated with shorter survival in 43 patients treated with the capecitabine-plus-oxaliplatin (CAPOX) regimen. LAT1 suppression in CRC cells inhibited the proliferation potency and oxaliplatin-induced activation of mTOR signaling, and improved oxaliplatin sensitivity. LAT1 evaluation before adjuvant treatment may therefore be a sensitive marker for oxaliplatin-based regimens. Moreover, LAT1 may be a promising target for patients with refractory CRC.

HLA Class I Expression Is Associated with DNA Damage and Immune Cell Infiltration into Dysplastic and Neoplastic Lesions in Ulcerative Colitis.

Human leukocyte antigen class I (HLA-I) is considered a genetic pathogen for ulcerative colitis (UC). This study aimed to investigate the significance of DNA damage and HLA-I expression in infiltrating immune cells and immune checkpoint protein PD-L1 expression in dysplasia/colitic cancer (CC) and sporadic colorectal cancer (SCRC). We performed immunohistochemical staining for HLA-I, PD-L1, γH2AX (DNA damage marker), and immune cell markers such as CD8, FOXP3, CD68, and CD163 (in surgically resected specimens from 17 SCRC patients with 12 adjacent normal mucosa (NM) and 9 UC patients with 18 dysplasia/CC tumors. The ratio of membrane HLA-I-positive epithelial cells in UC and dysplasia/CC tissues was significantly higher than that in NM and SCRC. High HLA-I expression in dysplasia/CC was associated with high positivity of γH2AX and PD-L1 expression compared to SCRC. The infiltration of CD8-positive T cells and CD68-positive macrophages in HLA-I-high dysplasia/CC was significantly higher than in UC and SCRC. Dysplasia/CC specimens with DNA damage exhibited high levels of HLA-I-positive epithelial cells with high CD8- and CD68-positive immune cell infiltration compared to UC and SCRC specimens. Targeting DNA damage in UC may regulate immune cell infiltration, immune checkpoint proteins, and carcinogenesis by modulating DNA damage-induced HLA-I antigen presentation.

Preoperative evaluation of oral hygiene may predict the overall survival of patients with esophageal cancer.

BACKGROUND: Previously, the association between tooth loss and prognosis after esophagectomy was reported; however, the presence of periodontal disease has not been assessed. This study investigated the association between the degree of oral hygiene, as evaluated by tooth loss and periodontal disease, and the prognosis of patients with esophageal cancer. METHODS: A total of 163 esophageal cancer patients who underwent surgery with perioperative oral care and examination were enrolled. We assessed the periodontal pocket depth for the presence of periodontal disease and established a periodontal pocket index, defined as the sum of the periodontal pocket depth of the remaining tooth divided by the total count of the remaining teeth. Patients were divided into three groups: Group A (tooth loss < 13 and periodontal pocket index < 3.67); Group B (tooth loss < 13 and periodontal pocket index ≥ 3.67); and Group C (tooth loss ≥ 13). Overall survival and cancer-specific survival were analyzed, and a multivariate analysis was performed. RESULTS: There was a significant difference in the 5-year overall survival rates between the groups (A:B:C = 74.8%:62.8%:50.5%; p = 0.0098), but not in the 5-year cancer-specific survival rates (A:B:C = 80.2%:64.2%:62.2%; p = 0.0849). In multivariate analysis, oral hygiene (tooth loss < 13 and periodontal pocket index ≥ 3.67 + tooth loss ≥ 13; p = 0.041) was a significant independent poor prognostic factor for overall survival. CONCLUSIONS: Oral evaluation, focusing on tooth loss and periodontal disease, is meaningful in predicting the long-term prognosis of postoperative esophageal cancer patients.

ASO Author Reflections: Impact of the Ratio of the Visceral Fat Area (VFA) to Psoas Muscle Area (PMA) (V/P Ratio) on Survival for Patients with Surgically Resected Esophageal Cancer.

PAST: The true impact of co-occurring muscle mass reduction and fat accumulation on patients with surgically resected esophageal cancer (EC) remains controversial. PRESENT: The current study defined reduction in muscle mass and excess body adiposity as the ratio of the visceral fat area (VFA) to the psoas muscle area (V/P ratio) on the same axial computed tomography slice at the third lumbar vertebra (L3). A high V/P ratio was associated with greater age (p = 0.03), higher body mass index (BMI) (p < 0.001), larger VFA (p < 0.001), and increased age-adjusted Charlson comorbidity index (ACCI) (p = 0.005). Multivariate analysis showed a high V/P ratio to be an independent prognostic factor for poor overall survival (OS) of EC patients who underwent surgery (p = 0.003). The prognostic value of the V/P ratio still was significant for EC patients with a BMI lower than 25 kg/m2. FUTURE: A high V/P ratio was an independent prognostic factor for OS of EC patients who underwent surgery, even BMI-defined non-obese EC patients. The V/P ratio as a surrogate marker of relative muscle mass reduction and fat accumulation may have prognostic value for EC patients regardless of body composition differences.

Impact of the Ratio of Visceral Fat Area (VFA) to Psoas Muscle Area (PMA) (V/P Ratio) on Survival for Surgically Resected Esophageal Cancer.

BACKGROUND: The synergic effects of muscle mass reduction with excess body adiposity in surgically resected esophageal cancer (EC) patients remains controversial, especially in non-obese patients. METHODS: One hundred and six patients with EC who underwent surgery between 2006 and 2014 were included in this study. Reduction in muscle mass and excess body adiposity were defined as the ratio of visceral fat area (VFA) to psoas muscle area (PMA) (V/P ratio) on the same axial computed tomography (CT) slice at the third lumbar vertebra (L3). RESULTS: A high V/P ratio was associated with greater age (p = 0.03), higher body mass index (BMI) (p < 0.001), higher VFA (p < 0.001), and increased age-adjusted Charlson comorbidity index (ACCI) (p = 0.005). Multivariate analysis revealed a high V/P ratio to be an independent prognostic factor for poor overall survival (OS) in EC patients who underwent surgery (p = 0.003). The prognostic value of the V/P ratio was still significant in EC patients with a BMI < 25. CONCLUSIONS: A high V/P ratio was associated with poor survival in surgically resected EC patients, even in non-obese patients. The V/P ratio as a surrogate marker of relative muscle mass reduction and fat accumulation may have prognostic value in EC patients regardless of body composition differences.

Changes in the Gustave Roussy Immune Score as a Powerful Prognostic Marker of the Therapeutic Sensitivity of Nivolumab in Advanced Gastric Cancer: A Multicenter, Retrospective Study.

BACKGROUND: Identification of positive biomarkers for the effects of nivolumab on patients with advanced gastric cancer (AGC) is significant. The Gustave Roussy Immune Score (GRIm-s) is associated with therapeutic resistance of immune checkpoint inhibitors (ICIs) in other cancers. This multicenter, retrospective study was designed to analyze the association of GRIm-s with therapeutic sensitivity of nivolumab in patients with AGC. METHODS: We reviewed 58 patients with AGC treated with nivolumab from October 2017 to November 2018 at five participating institutions. We performed blood tests before the start of nivolumab and after administration of two courses. We evaluated the correlation between the best overall response and GRIm-s. Additionally, we focused on the changes in GRIm-s before the start of nivolumab and after administration of two courses. RESULTS: Of the 58 patients, 21 (36.2%) were classified into the disease control (DC) group and 37 (63.8%) into the progressive disease (PD) group. GRIm-s before nivolumab treatment did not correlate with the best therapeutic response (p = 0.086). However, GRIm-s after two courses of nivolumab showed that significantly more PD cases were in the high-risk group (p < 0.0001). After two courses of nivolumab, overall survival was significantly worse in the high-risk group (p < 0.0001). For progression-free survival, the high-risk group had a significantly worse prognosis both before (p = 0.04) and after two courses of nivolumab treatment (p < 0.0001). CONCLUSIONS: GRIm-s after two courses of nivolumab and its changes compared to pretreatment values proved beneficial in predicting nivolumab sensitivity.

PROX1 Was Associated with LGR5 and Wnt Signaling and Contributed to Poor Prognosis in Gastric Cancer.

INTRODUCTION: We investigated whether the expression of prospero homeobox protein-1 (PROX1) in gastric cancer (GC) could be a prognostic marker. We also focused on the relationship between PROX1 and LGR5 and Wnt/ß-catenin activity in GC. METHODS: A total of 196 patients who underwent potentially curative surgery were collected and reviewed retrospectively. Immunohistochemistry was conducted and evaluated the expression PROX1, LGR5, Wnt3a, and ß-catenin expression. And we evaluated the relationship between PROX1 expression and clinicopathological features. RESULTS: The PROX1 low-expression group consisted of 105 patients (53.6%) and the high-expression group consisted of 91 patients (46.4%). For LGR5 expression, 76 patients (38.8%) were classified as low-expression, and 120 patients (61.2%) were classified as high-expression. The PROX1 low-expression group was significantly younger (p = 0.0095), had more intestinal type (p = 0.014), and had smaller tumor size (p = 0.013). The PROX1 high-expression group was significantly correlated with high LGR5 expression (p < 0.0001) and high Wnt3a expression (p = 0.012). In addition, there were significantly more cases of postoperative recurrence in the PROX1 high-expression group (p = 0.013). CONCLUSION: Our findings demonstrate that PROX1 correlated with the cancer stemness markers LGR5 and Wnt3a signaling in GC and had a poor prognosis including postoperative recurrence.

Clinical features as potential prognostic factors in patients treated with nivolumab for highly pretreated metastatic gastric cancer: a multicenter retrospective study.

BACKGROUND: Although nivolumab (anti-programmed cell death-1 antibody) is a promising approach for advanced gastric cancer (AGC), the response rate remains limited. The aim of this multicenter retrospective study was to determine if clinical features could serve as prognostic factors of the efficacy of nivolumab in patients with AGC. METHODS: Fifty-eight patients with AGC who were treated with nivolumab as a third or later line from October 2017 to December 2018 at any of five clinical sites were enrolled in the study. The correlation between the best overall response and clinical features was investigated. Overall survival and progression-free survival after initiation of nivolumab were calculated and clinical features that could be predictors of the prognosis were sought. RESULTS: The disease control rate (DCR) for nivolumab was 36.2% and was significantly correlated with performance status (p = 0.021), metastasis to one organ (p = 0.006), and grade 2 or higher immune-related adverse events (p = 0.027). There was also a significant association between response to nivolumab and ability to receive subsequent chemotherapy (p = 0.022). In the analysis of overall survival, the following variables were identified as being significantly associated with a poor outcome: Eastern Cooperative Oncology Group performance status ≥1, prior treatment with trastuzumab, no immune-related adverse events, lack of a response to nivolumab, and inability to receive subsequent chemotherapy. CONCLUSION: The findings of this study suggest that nivolumab may be ineffective for AGC in patients with poor performance status and those with a history of treatment with trastuzumab.

Preoperative Risk Factors and Prognostic Impact of Postoperative Complications Associated with Total Gastrectomy.

INTRODUCTION: We evaluated the risk factors for patients with gastric cancer (GC) undergoing total gastrectomy (TG) that predict postoperative complications, including anastomotic leakage, postoperative pneumonia, and heart disease. METHODS: We collected 106 patients who received TG for GC between May 2009 and May 2017 at Gunma University Graduate School of Medicine, including clinicopathologic, surgical, postoperative complication, laboratory test, and physiologic test data. RESULTS: Of 106 patients, 92 (86.8%) had no complications, and 14 (13.2%) had complications. Univariate analyses revealed that a high American Society of Anaesthesiologists physical status (ASA-PS) and neutrophil-lymphocyte ratio (NLR) of ≥3.5 significantly correlated with postoperative complications. Multivariate analyses showed that high ASA-PS was an independent prognostic factor of postoperative complications. The cancer recurrence rate was 34.8% in the noncomplication group and 71.4% in the complication group. CONCLUSION: Patients with postoperative complications are prone to recurrence and poor prognosis. For patients with high-risk GC with poor ASA-PS and high NLR, more thorough perioperative management is essential.

Retrospective study of online ligation student practice incorporating flipped learning into e-learning.

PURPOSE: Flipped learning has been applied in various fields, including medical professional education. E-learning is compatible with flipped learning; however, it is considered to be unsuitable for providing training on surgical techniques. In this study, we retrospectively examined the ligation performance of online students who underwent training with flipped learning incorporated into e-learning. METHODS: We conducted a retrospective study of the ligation practices of online students at the Department of General Surgery from March 2020 to June 2021. The subjects included 134 fourth- and fifth-year medical students from Gunma University School of Medicine. We conducted mid-term checks on the 8th day of practice and an examination on the 19th day. Two instructors independently evaluated and calculated scores using the original Global Rating Scale of Gunma University. We also conducted a questionnaire survey on the ligation practice of online students. RESULTS: The total average score of the three tasks was 12.4 for Instructor 1 and 12.0 for Instructor 2. All students had a passing score. The questionnaire survey showed that 70% of the students were trained in ligation at the time of the first evaluation. CONCLUSIONS: Our online training materials and training methods enabled the acquisition of ligation skills by students who had not previously received ligation training.

High L-Type Amino Acid Transporter 1 Levels Are Associated with Chemotherapeutic Resistance in Gastric Cancer Patients.

INTRODUCTION: We investigated whether the expression of L-type amino acid transporter 1 (LAT-1) in clinical gastric cancer (GC) patients could predict patient therapeutic response to postoperative adjuvant chemotherapy. METHODS: Immunohistochemistry was used to investigate LAT-1, CD98, and phosphorylated-mammalian target of rapamycin (p-mTOR) expression in 111 GC patients. To clarify whether LAT-1 influences the therapeutic effects of chemotherapy, the correlation between disease-free survival rates and LAT-1 was determined in 2 groups: 59 patients who did not undergo postoperative adjuvant chemotherapy and 52 patients who did undergo postoperative adjuvant chemotherapy. RESULTS: LAT-1 was significantly correlated with CD98 and p-mTOR expressions. We did not find any statistically significant correlation between LAT-1 and recurrence in the nontreated group. In contrast, a significant association was found between LAT-1 expression and disease-free survival in the chemotherapy group. Moreover, multivariate regression analysis demonstrated that LAT-1 was an independent predictor of disease-free survival in the postoperative adjuvant chemotherapy group (p = 0.012). CONCLUSION: Our findings demonstrate that LAT-1 is a useful predictive marker for a successful postoperative adjuvant chemotherapy treatment.

Role of PD-L1 Expression during the Progression of Submucosal Gastric Cancer.

INTRODUCTION: Programmed death-ligand 1 (PD-L1) expression is a prognostic marker for gastric cancer that correlates with tumor diameter and depth of penetration. But the role of PD-L1 and mechanism(s) employed in the initial phase of invasion in early gastric cancer is yet to be understood. OBJECTIVE: This study aims to elucidate the role of PD-L1 during the progression of gastric cancer, specifically invading the submucosa beyond the lamina muscularis mucosa. METHODS: Using 107 patients with pathological submucosal gastric cancer, we determined the expression of PD-L1 based on the staining of the cell membrane or cytoplasm of tumor cells in the central and invasive front of the tumor. Samples were categorized into 3 groups based on the intensity of PD-L1 expression. CD8+ lymphocytes expressing PD-1 and CD163+ macrophages were used to determine the number of cell nuclei at the invasive front, similar to PD-L1. CMTM6 levels were determined and used to stratify samples into 3 groups. RESULTS: PD-L1 expression was higher in the invasive front (26.2%) than in the central portion of the tumors (7.4%; p < 0.001). Moreover, lymphatic and vascular invasion were more frequently observed in samples with high levels of PD-L1 (lymphatic invasion: 60.7 vs. 35.4%, p = 0.0026, and vascular invasion: 39.3 vs. 16.5%, p = 0.0018). There was no correlation between PD-L1 expression and the levels of PD-1, CD8, CD163, and CMTM6. CONCLUSIONS: PD-L1-expressing cancer cells at the invasive front of gastric cancer influence the initial stages of tumor invasion and lymphovascular permeation in early-stage gastric cancers. Immune checkpoint signaling may be the driving force in the invasive front during the invasion of the submucosa beyond the lamina muscularis mucosa.

Prognostic significance of ß2-adrenergic receptor expression in patients with surgically resected colorectal cancer.

PURPOSE: The ß2-adrenergic receptor (ß2AR) is highly expressed in various human cancers. The prognostic significance of its expression in patients with colorectal cancer (CRC) remains unclear. The aim of this study was to assess the prognostic role of ß2AR expression in patients with surgically resected CRC. METHODS: One hundred and forty-seven patients with surgically resected CRC were examined using immunohistochemistry. The expression of ß2AR was assessed in the specimens of resected primary tumors. RESULTS: ß2AR was expressed in 52.3% of the patients' tumors. ß2AR expression was significantly associated with T factor, N factor, and tumor cell proliferation (Ki-67 labeling index). Univariate analysis demonstrated that T factor, N factor, tumor stage, lymphatic permeation, vascular invasion, perineural invasion, ß2AR expression, and Ki-67 labeling index were significant prognostic factors for worse disease-free survival (DFS); all but T factor were also significant predictors for worse overall survival (OS). Multivariate analysis confirmed that expression of ß2AR was a significant prognostic marker for predicting worse DFS and OS. CONCLUSION: ß2AR expression was identified as a significant independent prognostic factor in patients with surgically resected CRC.