Development and Validation Study of the Prognostic Impact of Deep Learning-Determined Myxoid Stroma After Neoadjuvant Chemotherapy in Patients with Esophageal Squamous Cell Carcinoma.

PURPOSE: This study was designed to investigate the prognostic significance of artificial intelligence (AI)-based quantification of myxoid stroma in patients undergoing esophageal squamous cell carcinoma (ESCC) surgery after neoadjuvant chemotherapy (NAC) and to verify its significance in an independent validation cohort from another hospital. METHODS: We evaluated two datasets of patients with pathological stage II or III ESCC who underwent surgery after NAC. Cohort 1 consisted of 85 patients who underwent R0 surgery for the primary tumor after NAC. Cohort 2, the validation cohort, consisted of 80 patients who received same treatments in another hospital. AI-based myxoid stroma was evaluated in resected specimens, and its area was categorized by using the receiver operating characteristic curve for overall survival (OS) of cohort 1. RESULTS: The F1 scores, which are the degree of agreement between the automatically detected myxoid stroma and manual annotations, were 0.83 and 0.79 for cohorts 1 and 2. The myxoid stroma-high group had a significantly poorer prognosis than the myxoid stroma-low group in terms of OS, disease-specific survival (DSS), and recurrence-free survival (RFS) in cohort 1. Comparable results were observed in cohort 2, where OS, DSS, and RFS were significantly affected by myxoid stroma. Multivariate analysis for RFS revealed that AI-determined myxoid stroma-high was one of the independent prognostic factors in cohort 1 (hazard ratio [HR] 1.97, p = 0.037) and cohort 2 (HR 4.45, p < 0.001). CONCLUSIONS: AI-determined myxoid stroma may be a novel and useful prognostic factor for patients with pathological stage II or III ESCC after NAC.

Risk of hepatic steatosis with the preoperative treatment of pancreatic cancer and the short-term postoperative outcomes.

PURPOSE: We investigated whether the preoperative treatment of patients with pancreatic cancer is a risk factor for hepatic steatosis (HS), and whether preoperative HS affects the short-term postoperative outcomes. METHODS: Patients who underwent radical surgery for pancreatic cancer between 2010 and 2023 were enrolled. The patients' medical records were reviewed. Albumin and carbohydrate antigen 19-9 were measured before and after chemotherapy in the patients who received preoperative chemotherapy. A logistic regression univariate analysis was performed to analyze the factors associated with new-onset HS. RESULTS: A total of 230 patients who underwent surgery were included. HS was observed on the date of surgery in 11 (10%) and two (2%) patients with and without preoperative chemotherapy, respectively. Female sex, initially borderline resectable or unresectable disease, history of cholangitis, presence of PEI, long-term (≥ 3 months) biliary drainage, preoperative chemotherapy, and serum albumin ≥ 3.9 mg/dl before chemotherapy were identified as risk factors for HS. The incidence of postoperative morbidity did not differ between the patients with and without preoperative steatosis. CONCLUSIONS: Preoperative chemotherapy, a history of cholangitis, the presence of PEI, and ≥ 3 months' duration of biliary drainage were risk factors for the development of HS before surgery for pancreatic cancer. However, preoperative HS did not affect the short-term postoperative outcomes.

Impact of Preoperative Tumor Size on Prognosis of Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinomas.

BACKGROUND: Tumor size (TS) is a well-established prognostic factor of pancreatic ductal adenocarcinoma (PDAC). However, whether a uniform treatment strategy can be applied for all resectable PDACs (R-PDACs) and borderline resectable PDACs (BR-PDACs), regardless of TS, remains unclear. This study aimed to investigate the impact of preoperative TS on surgical outcomes of patients with R-PDACs and BR-PDACs. METHODS: Chart data from three institutions were reviewed to select patients who underwent pancreatectomy for R-PDACs and BR-PDACs between January 2006 and December 2020. The patients were divided into TSsmall and TSlarge groups according to a TS cutoff value determined for each of R- and BR-PDAC using the minimum P value approach for the risk of R1 resection. RESULTS: TS of 35 mm and 24 mm was the best cutoff value in R-PDAC and BR-PDAC, respectively. The R1 rate was higher in the TSlarge than TSsmall group, in both R- (n = 35, 37% versus n = 294, 19%; P = 0.011) and BR-PDAC (n = 89, 37% versus n = 27, 15%; P = 0.030). Overall survival was significantly better in the TSsmall than TSlarge group in R-PDAC (38.2 versus 12.1 months; P < 0.001), but comparable between the two groups in BR-DPAC (21.2 versus 22.7 months; P = 0.363). Multivariate analysis revealed TS > 35 mm as an independent predictor of worse survival in patients with R-PDAC. CONCLUSION: Larger TS was associated with a higher R1 rate and is a worse prognostic factor in patients with R-PDAC.

Impact of retention index on the neoadjuvant chemotherapy effect and the prognosis in oesophageal cancer.

OBJECTIVE: The relationship between retention index calculated from dual-time point 18F-fluorodeoxyglucose positron emission tomography-computed tomography and oesophageal cancer prognosis remains unknown. This study aimed to determine usefulness of retention index as a predictor of long-term prognosis of oesophageal cancer and neoadjuvant chemotherapy efficacy. METHODS: A total of 151 patients with oesophageal cancer who underwent esophagectomy were evaluated retrospectively in this study. We acquired positron emission tomography scans 60 and 120 min (SUVmax1 and SUVmax2, respectively) after the intravenous administration of 3.7 Mbq/kg 18F-fluorodeoxyglucose. The patients were divided into two groups: high-retention index (retention index ≥29%, 107 patients) and low-retention index (retention index <29%, 44 patients). Retention index was calculated as follows: retention index (%) = [(SUVmax2 - SUVmax1)/SUVmax1] × 100. RESULTS: The overall survival and relapse-free survival rates in the high-retention index group were significantly lower than those in the low-retention index group (P < 0.001). Our multivariate analysis identified that the high-retention index group contained independent risk factors for overall survival (hazard ratio: 2.44, P = 0.009) and relapse-free survival (hazard ratio: 2.61, P = 0.002). The high-retention index group exhibited a lower partial response rate to neoadjuvant chemotherapy evaluated by computed tomography (P < 0.001) and a lower pathological therapeutic effect in the resected specimen (P = 0.019) than the low-retention index group. CONCLUSIONS: The retention index was associated with neoadjuvant chemotherapy responses and long-term prognosis for oesophageal cancer.

Clinical significance of postoperative subcutaneous emphysema after video-assisted thoracoscopic surgery for esophageal cancer.

BACKGROUND: Postoperative subcutaneous emphysema (SE) is a possible complication of thoracoscopic or laparoscopic surgery. This study investigated the risk factors and clinical significance of SE after video-assisted thoracoscopic surgery for esophageal cancer (VATS-e). METHODS: This study included 135 patients who underwent VATS-e with artificial CO2 pneumothorax. Based on the X-ray images on the first postoperative day, patients were divided into two groups: N/L group (no SE or SE localized at the thoracic area, n = 65) and SE group (SE extended to the cervical area, n = 70). We compared clinicopathological features, surgical findings, and short-term outcomes between the two groups. RESULTS: In SE group, there were more patients who received neoadjuvant chemotherapy compared to N/L group. SE group had significantly lower preoperative body mass index. SE group had more frequently two-lung ventilation than N/L group. Multivariate analysis demonstrated that low BMI, NAC, and two-lung ventilation were independent risk factors for SE extended to the cervical area. Although pulmonary complication was relatively frequent in SE group, there were no significant differences in surgical outcomes between two groups, and all patients had SE disappeared within 21 days without serious complications. CONCLUSIONS: Despite extension to the cervical area, SE had a modest impact on the short-term result of VATS-e with artificial CO2 pneumothorax.

Prognostic impact of desmoplastic reaction in esophageal squamous cell carcinoma patients with neoadjuvant therapy.

AIM: This study aimed to examine the prognostic value of desmoplastic reaction (DR) in esophageal squamous cell carcinoma (ESCC), particularly in patients who received neoadjuvant therapy, such as chemotherapy (NAC) or chemoradiotherapy (NACRT). METHOD: In total, 153 patients with pStage II/III ESCC were included in this study. Ninety-one patients received neoadjuvant therapy (NAC, 70; NACRT, 21). Patients were classified according to three DR categories based on the presence of keloid-like collagen and/or myxoid stroma. RESULTS: In total, 50, 50, and 53 patients were classified as having mature, intermediate, and immature DR, respectively. The weighted kappa coefficient was 0.623 in the patients with preoperative treatments and 0.782, in those without. The 5-year disease-specific survival (DSS) rates in patients with intermediate/immature DR was significantly worse than those with mature DR (40.7% vs. 73.3%, p < 0.001). Similarly, the 5-year DSS rate in patients with intermediate/immature DR was significantly worse than those with mature DR in a study of patients who received neoadjuvant therapy (46.7% vs. 71.2%, p = 0.009). Multivariate analysis revealed that DR (hazard ratio [HR]: 3.15, 95% confidence interval [CI] 1.58-6.27, p = 0.001), along with N factors, was an independent risk factor for DSS. Moreover, multivariate analysis of patients who received neoadjuvant therapy revealed only DR (HR: 2.47, 95% CI 1.02-5.96, p = 0.045) as independent risk factors for DSS. CONCLUSION: The DR classification was a valuable prognostic factor not only in the ESCC patients without neoadjuvant therapy but also in those with neoadjuvant therapy.

Cancer-associated fibroblasts at the unfavorable desmoplastic stroma promote colorectal cancer aggressiveness: Potential role of ADAM9.

The tumor microenvironment plays a key role in cancer aggressiveness. Desmoplastic reaction (DR), morphologically classified as Mature, Intermediate and Immature types, has previously been shown to be highly prognostic in colorectal cancer (CRC) and it consists to a large extent of cancer-associated fibroblasts (CAFs). The aim of our study was to characterize the molecular background of DR and understand the effects of CAFs in tumor aggressiveness. The prognostic significance of DR was initially examined in 1497 patients. Then CAFs originating from patient tissues with different DR types were isolated and their impact on tumor growth was examined both in vitro and in vivo. DR was shown to be highly prognostic, with patients within the Immature DR group conferring the worst relapse-free survival. The conditioned media of CAFs from tumor with Immature-type DR (CAFsImmature ) significantly increased proliferation and migration of CRC cell lines and growth of CRC-derived organoids compared to that of CAFs from Mature-type DR (CAFsMature ). Subcutaneous or orthotopic implantation of CRC cells together with CAFsImmature in mice significantly promoted tumor growth and dissemination compared to implantation with CAFsMature . Systematic examination of the expression of "a disintegrin and metalloproteinases" (ADAMs) in CAFs isolated from CRC tissues showed that the secreted isoform of ADAM9 (ADAM9s) was significantly higher in CAFsImmature than in CAFsMature . Knockdown of ADAM9s in CAFsImmature abrogated the promoting effects on CRC cell proliferation and migration. CAFs-derived ADAM9s is implicated in deteriorating survival in CRC patients with Immature-type DR by increasing tumor cell proliferation and dissemination.

Potential mechanisms of tumor progression associated with postoperative infectious complications.

There is increasing evidence that postoperative infectious complications (PICs) are associated with poor prognosis after potentially curative surgery. However, the role that PICs play in tumor development remains unclear. In this article, we reviewed the literature for novel insights on the mechanisms of cancer progression associated with PICs. The Medline and EMBASE databases were searched for publications regarding the role of suppression of antitumor immunity by PIC in tumor progression and selected 916 manuscripts were selected for this review. In addition, a summary of the authors' own experimental data from this field was set in the context of current knowledge regarding cancer progression under septic conditions. Initially, sepsis/microbial infection dramatically activates the systemic immune system with increases in pro-inflammatory mediators, which results in the development of systemic inflammatory response syndrome; however, when sepsis persists in septic patients, a shift toward an anti-inflammatory immunosuppressive state, characterized by macrophage deactivation, reduced antigen presentation, T cell anergy, and a shift in the T helper cell pattern to a predominantly TH2-type response, occurs. Thus, various cytokine reactions and the immune status dynamically change during microbial infection, including PIC. We proposed three possible mechanisms for the tumor progression associated with PIC: first, a mechanism in which microbes and/or microbial PAMPs may be directly involved in cancer growth; second, a mechanism in which factors released from immunocompetent cells during infections may affect tumor progression; and third, a mechanism in which factors suppress host tumor immunity during infections, which may result in tumor progression. A more detailed understanding by surgeons of the immunological features in cancer patients with PIC can subsequently open new avenues for improving unfavorable long-term oncological outcomes associated with PICs.

Neoadjuvant therapy alters the collagen architecture of pancreatic cancer tissue via Ephrin-A5.

BACKGROUND: The treatment of pancreatic cancer (PDAC) remains clinically challenging, and neoadjuvant therapy (NAT) offers down staging and improved surgical resectability. Abundant fibrous stroma is involved in malignant characteristic of PDAC. We aimed to investigate tissue remodelling, particularly the alteration of the collagen architecture of the PDAC microenvironment by NAT. METHODS: We analysed the alteration of collagen and gene expression profiles in PDAC tissues after NAT. Additionally, we examined the biological role of Ephrin-A5 using primary cultured cancer-associated fibroblasts (CAFs). RESULTS: The expression of type I, III, IV, and V collagen was reduced in PDAC tissues after effective NAT. The bioinformatics approach provided comprehensive insights into NAT-induced matrix remodelling, which showed Ephrin-A signalling as a likely pathway and Ephrin-A5 (encoded by EFNA5) as a crucial ligand. Effective NAT reduced the number of Ephrin-A5+ cells, which were mainly CAFs; this inversely correlated with the clinical tumour shrinkage rate. Experimental exposure to radiation and chemotherapeutic agents suppressed proliferation, EFNA5 expression, and collagen synthesis in CAFs. Forced EFNA5 expression altered CAF collagen gene profiles similar to those found in PDAC tissues after NAT. CONCLUSION: These results suggest that effective NAT changes the extracellular matrix with collagen profiles through CAFs and their Ephrin-A5 expression.

Deep-learning-based classification of desmoplastic reaction on H&E predicts poor prognosis in oesophageal squamous cell carcinoma.

AIMS: Desmoplastic reaction (DR) categorisation has been shown to be a promising prognostic factor in oesophageal squamous cell carcinoma (ESCC). The usual DR evaluation is performed using semiquantitative scores, which can be subjective. This study aimed to investigate whether a deep-learning classifier could be used for DR classification. We further assessed the prognostic significance of the deep-learning classifier and compared it to that of manual DR reporting and other pathological factors currently used in the clinic. METHODS AND RESULTS: From 222 surgically resected ESCC cases, 31 randomly selected haematoxylin-eosin-digitised whole slides of patients with immature DR were used to train and develop a deep-learning classifier. The classifier was trained for 89 370 iterations. The accuracy of the deep-learning classifier was assessed to 30 unseen cases, and the results revealed a Dice coefficient score of 0.81. For survival analysis, the classifier was then applied to the entire cohort of patients, which was split into a training (n = 156) and a test (n = 66) cohort. The automated DR classification had a higher prognostic significance for disease-specific survival than the manually classified DR in both the training and test cohorts. In addition, the automated DR classification outperformed the prognostic accuracy of the gold-standard factors of tumour depth and lymph node metastasis. CONCLUSIONS: This study demonstrated that DR can be objectively and quantitatively assessed in ESCC using a deep-learning classifier and that automatically classed DR has a higher prognostic significance than manual DR and other features currently used in the clinic.

Therapeutic efficacy of dose-reduced adjuvant chemotherapy with S-1 in patients with pancreatic cancer: a retrospective study.

BACKGROUND: S-1 adjuvant chemotherapy is the standard treatment in Asia for resectable pancreatic ductal adenocarcinoma. The relative dose intensity of adjuvant chemotherapy influences survival in pancreatic cancer but does not precisely reflect treatment schedule modifications. We investigated the effects of total dose intensity of S-1 adjuvant chemotherapy on the survival of patients with pancreatic cancer and the permissible dose reduction. METHODS: Patients who underwent surgical resection during 2011-2019 for pancreatic cancer were selected. We determined the total dose intensity cut-off value that predicted tumor recurrence within 2 years postoperatively using receiver operating characteristic curves and compared the outcomes between the high and low total dose intensity groups. RESULTS: Patients with total dose intensity ≥ 62.5% (n = 53) showed significantly better overall survival than those with total dose intensity < 62.5% (n = 16) (median survival time: 53.3 vs. 20.2 months, P < 0.001). The median survival of patients without adjuvant chemotherapy (total dose intensity = 0, n = 28) was 24.8 months. Univariate analysis identified lymphatic involvement (P = 0.035), lymph node metastasis (P = 0.034), and total dose intensity (P < 0.001) as factors affecting survival. On multivariate analysis, total dose intensity (P < 0.001) was an independent predictor of worse survival. CONCLUSIONS: Maintaining a total dose intensity of at least 60% in S-1 adjuvant chemotherapy seems important to achieve a long postoperative survival in patients with pancreatic cancer.

Clinical Relevance of Tissue and Serum Human Epidermal Growth Factor Receptor 2 Expression in Patients With Esophageal Squamous Cell Carcinoma.

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.

Proposal for a tumor budding predictive score derived from endoscopic biopsy samples in colorectal cancer.

BACKGROUND: In colorectal cancer, tumor budding is highlighted as both a prognostic indicator and a predictor of chemosensitivity. However, tumor budding has a serious drawback because of unattainable preoperative assessment, thereby, making it not applicable to decision-making on treatment strategies. Recently, high expressions of seven genes (i.e., MSLN, SLC4A11, WNT11, SCEL, RUNX2, MGAT3, and FOXC1) were shown to be associated with high-budding colorectal cancers. This study aimed to propose a budding prediction system using selected RNAs extracted from biopsy specimens. METHODS: The RNA expression levels in 86 surgically resected samples and in 104 samples obtained by colonoscopy before surgery were investigated. RESULTS: The tumor surface expressions of four exclusive genes (i.e., MSLN, SLC4A11, SCEL, and MGAT3) were correlated with the tumor budding grade. Subsequently, the logit P value calculated by multiple logistic regression analysis using the four surface gene expressions was set as the following budding predictive score: Logit (P) = - 0.55 + 0.27*MSLN + 0.16*SLC4A11 + 0.06*MGAT3 + 0.21*SCEL. The effectiveness of the model using colorectal cancer biopsy samples was well corroborated prospectively. CONCLUSION: The budding predictive score that we developed using endoscopic biopsy specimens was clarified to have a high potential for preoperative use.

Characteristics of false-positive lesions in evaluating colorectal liver metastases on gadoxetic acid-enhanced magnetic resonance imaging.

PURPOSE: Gadoxetic acid-enhanced MRI (Gd-EOB-MRI) shows higher sensitivity for colorectal liver metastases (CRLM) than contrast-enhanced computed tomography (CECT). However, the details of false-positive lesions for each imaging modality are unknown. METHODS: Cases undergoing hepatectomy for CRLM following a preoperative evaluation with both CECT and Gd-EOB-MRI between July 2008 and December 2016 were reviewed. The false-positive and false-negative rates were assessed for each modality, and the characteristics of false-positive lesions were evaluated. RESULTS: We evaluated 275 partial hepatectomies in 242 patients without preoperative chemotherapy. Among the 275 hepatectomies, 546 lesions were recognized by CECT and/or Gd-EOB-MRI. The false-positive rates for CECT and Gd-EOB-MRI were 4% (18/422) and 7% (37/536), respectively. The size of false-positive lesions was significantly smaller than that of correctly diagnosed lesions (median: 28 mm [3-120 mm] vs 7.6 mm [320 mm], P < 0.001). Compared with the 233 correctly diagnosed lesions ≤ 20 mm in diameter, false-positive lesions were more frequently located near the liver surface or vasculobiliary structures than true lesions (33/37 [89%] vs 149/233 [64%], respectively; P = 0.0021). CONCLUSION: Gd-EOB-MRI had a 7% false-positive rate. A small size and tumor location near the surface or near vasculobiliary structures were associated with false positivity.

A multicenter phase II trial evaluating the efficacy of bevacizumab plus mFOLFOX6 for R0 surgical resection in advanced colorectal liver metastases harboring mutant-type KRAS: NEXTO-mt trial.

BACKGROUND: The effect of bevacizumab plus mFOLFOX6 on downsizing of liver metastases for curative resection has not been well assessed for patients with advanced colorectal liver metastases (CRLMs). This multicenter phase II trial aimed to examine the efficacy and safety of bevacizumab plus mFOLFOX6 for advanced CRLMs harboring mutant-type KRAS. METHODS: Patients with advanced CRLMs (tumor number of ≥5 and/or technically unresectable) harboring mutant-type KRAS were included. Surgical indication was evaluated every 4 cycles of bevacizumab plus mFOLFOX6. Liver resection was planned if the CRLMs were resectable. The primary endpoint was R0 resection rate. The secondary endpoints included overall survival (OS), recurrence-free survival, progression-free survival, and safety. RESULTS: Between 2013 and 2017, 29 patients from six centers were registered. The rates of complete and partial responses were 0% and 62.1%, respectively. R0 and R1 resections were performed in 19 and 1 patient, respectively (R0 resection rate: 65.5%). No mortality occurred. During the median follow-up of 30.7 months, the 3-year OS rate for all the patients was 64.4% with the median survival of 49.1 months. CONCLUSION: For advanced CRLMs harboring mutant-type KRAS, bevacizumab plus mFOLFOX6 achieved a high R0 resection rate, leading to favorable survival.

Mesothelin Expression is Correlated with Chemoresistance in Stage IV Colorectal Cancer.

BACKGROUND: Mesothelin (MSLN) is a cell-surface glycoprotein present on mesothelial cells; its expression in several epithelial cancers generally portends an unfavorable prognosis. We investigated MSLN as a surrogate chemopredictive biomarker and examined the impact of MSLN expression in stage IV colorectal cancer (CRC). METHODS: We recruited 254 patients with CRC who received systemic chemotherapy following primary tumor resection between 2000 and 2019. Resected specimens were immunostained for MSLN and stratified by MSLN expression. The associations of tumor MSLN expression with tumor response in metastatic lesions and survival were evaluated. RESULTS: Of the 247 patients with stage IV CRC, 41 (16.1%) and 213 (83.9%) had high and low MSLN expression, respectively. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, the investigator-assessed objective response rate was 22.0% in the high MSLN expression group and 45.5% in the low MSLN expression group (p = 0.0050). The disease control rates in these groups were 65.9% and 85.9%, respectively (p = 0.00019). In the patients with high MSLN expression, the conversion rate among those with initially unresectable metastases was 0% versus 14% in the patients with low MSLN expression (p = 0.0053). The median overall survival (OS) was 1.5 years (95% confidence interval [CI] 1.1-2.8) in the high MSLN expression group versus 2.6 years (95% CI 2.2-3.0) in the low MSLN expression group. The 3-year OS rates in these groups were 23.5 and 41.5%, respectively (p = 0.0120). CONCLUSIONS: High MSLN expression is correlated with chemoresistance and poor prognoses in stage IV CRC.

Correlation Between Immunoinflammatory Measures and Periostin Expression in Esophageal Squamous Cell Carcinoma: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Immunoinflammatory measures such as the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), and the C-reactive protein (CRP)-albumin ratio (CAR) are useful prognostic measures in various malignancies. However, no study has investigated the correlation of these measures with microenvironmental inflammation. Periostin (POSTN), a small extracellular matrix protein, strongly associates with cancer microenvironmental inflammation. The current study investigated the correlation of NLR, PLR, and CAR with periostin expression in esophageal squamous cell carcinoma (ESCC). METHODS: The study retrospectively evaluated preoperative NLR, PLR, and CAR hematologically and POSTN immunohistochemically in 171 patients. The correlation of immunoinflammatory measures, POSTN expression, and survival outcomes was measured. RESULTS: The study showed a significant correlation of POSTN-positive expression with poor overall survival (OS) (P < 0.0001) and recurrence-free survival (RFS) (P = 0.03). The POSTN-positive group had higher PLR (189.6 ± 8 vs. 159.3 ± 12; P = 0.04) and CAR (0.36 ± 0.06 vs. 0.14 ± 0.09; P < 0.05) than the POSTN-negative group, whereas NLR did not differ between the two groups (3.27 ± 0.19 vs. 2.65 ± 0.28; P = 0.07). The uni- and multivariate analyses showed that POSTN-positive expression (hazard ratio [HR], 1.595; 95% confidence interval [CI], 0.770-3.031; P = 0.03), CAR (HR, 1.663; 95% CI, 1.016-2.764; P = 0.03), gender (HR, 2.303; 95% CI, 1.067-6.019; P = 0.03), and tumor depth (HR, 1.957; 95% CI, 1.122-3.526; P = 0.01) were independent prognostic factors. CONCLUSIONS: Because POSTN-positive expression strongly correlates with immunoinflammatory measures, especially PLR and CAR, it is an independent prognostic factor in ESCC.

Lipopolysaccharide preconditioning reduces liver metastasis of Colon26 cells by enhancing antitumor activity of natural killer cells and natural killer T cells in murine liver.

BACKGROUND AND AIM: Lipopolysaccharide (LPS) preconditioning drastically augments bactericidal activity but reduces the host inflammatory response. Therefore, it may be beneficial to prevent postoperative infectious complications and mitigate host damage by surgical stress. Considering its clinical application, how LPS preconditioning influences the antitumor effect in the liver is an important issue. We then investigated the effect of LPS preconditioning on antitumor activity against Colon26 tumor cells in mice. METHODS: Lipopolysaccharide preconditioning was induced in mice by the intraperitoneal injection of 5 µg/kg LPS for three consecutive days. Intraportal inoculation of Colon26 cells, which express luminescent protein called Nano-lantern, was performed to evaluate the effect of LPS preconditioning on tumor liver metastasis. The antitumor activities of cytotoxic liver lymphocytes, especially natural killer (NK) cells and natural killer T (NKT) cells, against Colon26 cells were also examined in LPS preconditioned mice. RESULTS: Lipopolysaccharide preconditioning remarkably prevented liver metastasis of Colon26 cells, as observed by IVIS imaging system, and prolonged survival after tumor inoculation. LPS preconditioning increased the proportions and number of liver NK cells and NKT cells and augmented their intracellular perforin and granzyme B expression, while reducing their intracellular expression of IFN-γ. An in vitro antitumor cytotoxicity assay revealed that LPS preconditioning significantly augmented antitumor cytotoxicities of the liver NK cells and NKT cells, especially NKT cells, against Colon26 cells. CONCLUSIONS: Lipopolysaccharide preconditioning potently augmented antitumor cytotoxicity of liver NK cells and NKT cells, thereby improving mouse survival after intraportal inoculation of Colon26 tumor cells. It may be useful for perioperative care in oncological patients.

Preoperative fall risk assessment score as a prognostic factor in gastric cancer patients after gastrectomy.

OBJECTIVE: Falls are related to frailty, which is known as an unfavorable prognosticator of gastric cancer. In this study, we investigated the influence of the fall risk assessment score on short- and long-term prognoses in patients with gastric cancer after gastrectomy. METHODS: A total of 430 patients who underwent gastrectomy for gastric cancer were included in this retrospective study. The fall risk assessment score was scored by nursing staffs on admission. We investigated the relationships between the fall risk assessment score and clinicopathological findings, postoperative outcomes and prognoses. We assigned patients with a fall risk assessment score ≥7 to the high-risk group (92 cases, 21.4%) and those with a fall risk assessment score <6 to the low-risk group (338 cases, 78.6%). RESULTS: There were no significant differences between the two groups in pathological stage of gastric cancer and postoperative complications, but the high-risk group had significantly longer postoperative hospital stays than the low-risk group (P < 0.001). The overall and the relapse-free survival rates in the high-risk group were significantly lower than those in the low-risk group. The high-risk group was one of the independent poor prognostic factors for overall survival, with a hazard ratio of 2.91 (P ≤ 0.001) in univariate analysis and a hazard ratio of 2.74 (P = 0.008) in multivariate analysis. CONCLUSIONS: While the fall risk assessment score is an objective and easy-to-use method to assess fall risk and frailty, it may present a prognostic factor in gastric cancer.

Impact of postoperative infectious complications on adjuvant chemotherapy administration after gastrectomy for advanced gastric cancer.

BACKGROUND: The aim of this study was to investigate the impact of postoperative infectious complications on adjuvant chemotherapy administration in patients with gastric cancer. METHODS: A retrospective review of 308 patients who underwent curative resection for gastric cancer was performed. Patients were divided into two groups based on the presence (90 patients, 29.2%) or absence (218 patients, 70.8%) of postoperative infectious complications to analyze clinicopathological characteristics, treatment factors and survival. RESULTS: Fewer patients with postoperative infectious complication received adjuvant chemotherapy compared to those without postoperative infectious complication. The proportion of patients who started treatment within 6 weeks after surgery was significantly lower in patients with postoperative infectious complication. The treatment completion rate was significantly lower in patients with postoperative infectious complication. The number of treatment cycles and relative dose intensity was significantly lower in patients with postoperative infectious complication. In univariate analysis, only postoperative infectious complication was significantly associated with continuation of adjuvant chemotherapy. Multivariate analysis demonstrated tumor depth, nodal involvement, postoperative infectious complication and adjuvant chemotherapy were significantly associated with overall survival. CONCLUSION: Postoperative infectious complications are significantly associated with the delay of adjuvant chemotherapy and predict adverse clinical outcome in patients with gastric cancer.