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.

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.

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.

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.

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.

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.

A multicenter non-randomized phase III study of sentinel node navigation surgery for early gastric cancer.

This prospective multicenter non-randomized phase III study aims to evaluate the long-term outcome of sentinel node navigation surgery for early gastric cancer compared with conventional distal or total gastrectomy. Clinically diagnosed primary T1N0M0 gastric cancer patients with a single lesion (≤40 mm) and without previous endoscopic treatment will be enrolled in this study. Sentinel nodes are identified by dye and radioisotope tracers and are subjected to intraoperative rapid pathology. For patients with negative sentinel node metastasis, individualized surgery consisting of limited stomach resection and sentinel node basin dissection is performed, while standard gastrectomy with D2 lymph node dissection is employed for the positive sentinel node patients. A total of 225 patients will be accrued from 13 hospitals that have experience in sentinel node mapping. The primary endpoint is 5-year relapse-free survival. The secondary endpoints are overall survival, sentinel node detection rate, diagnostic accuracy for sentinel node, distribution of sentinel nodes and metastatic sentinel node/non-sentinel node, and postoperative quality of life.

Impact of Lymph Node Metastases Around the Superior Mesenteric Artery on Postoperative Outcomes of Pancreatic Head Cancer.

BACKGROUND: The neural plexus and lymph nodes around the superior mesenteric artery (LN#14), are the most frequent sites involved by pancreatic head cancer. However the influence of metastases to LN#14 on patients' prognosis has rarely been evaluated. METHODS: The patients who underwent pancreatectomy for pancreatic head cancer between January 2010 and December 2018 were selected. The patients with nodal metastases were classified into an LN#14 + or LN#14-group according to LN#14 metastasis. Clinical and pathological characteristics and prognosis were compared between the two groups. RESULTS: In total, 99 patients underwent pancreatectomy. Ninety-four patients were positive for lymph node metastases and 14 and 80 were classified as LN#14 + and LN#14 - , respectively. Postoperative median overall survival (OS) of the LN#14 + and LN#14 - groups was 10.2 and 31.1 months, respectively (P < 0.001). Median OS of the LN#14 + group was worse than that of patients with ≥ 4 metastatic nodes in the LN#14 - group (n = 35, 24.7 months, P = 0.002). In multivariate analysis, LN#14 + (hazard ratio [HR] = 3.89, 95% confidence interval [CI], 1.64-8.86) was one of the independent predictors of worse OS. CONCLUSION: It might be feasible to recognize LN#14 metastases as an important prognostic factor independently from other regional lymph node metastases.

Modified geriatric nutrition risk index as a prognostic predictor of esophageal cancer.

BACKGROUND: This study aimed to establish a simple and useful prognostic indicator for elderly esophageal cancer patients. We designed the modified geriatric nutrition risk index (mGNRI) using the inverse of C-reactive protein (CRP) instead of albumin and compared its prognostic value with those of the GNRI and other indices. METHODS: We included 128 patients aged > 65 years who underwent esophagectomy for esophageal cancer. We defined mGNRI as (1.489/CRP in mg/dL) + (41.7 × present/ideal body weight) and divided patients into two groups: the low-mGNRI (mGNRI < 70, n = 50) and high-mGNRI (mGNRI ≥ 70, n = 78) groups. We retrospectively examined the relationship between mGNRI and long-term prognosis. RESULTS: The low-mGNRI group had more advanced cancer by stage, higher rates of recurrence, and earlier recurrence than the high-mGNRI group. Univariate analysis identified the following factors as significantly associated with poor overall survival (OS): a lower American society of anesthesiologist performance status (ASA-PS), male gender, CRP-albumin ratio ≥ 0.1, CRP ≥ 1.0, low-mGNRI, tumor depth ≥ T3, Charlson comorbidity index ≥ 2, tumor size ≥ 40 mm, and age > 75 years. A low-mGNRI, ASA-PS 3, age > 75 years, and tumor depth ≥ T3 were independent unfavorable prognostic factors for OS. A low-mGNRI was an independent poor prognostic factor for relapse-free survival. We performed model selection analysis to identify the most clinically useful indices; mGNRI was the best predictive model. CONCLUSION: mGNRI in patients with esophageal cancer correlated with early recurrence and was a useful independent prognostic factor.

Prognostic Impact of Budding Grade in Patients With Residual Liver Recurrence of Colorectal Cancer After Initial Hepatectomy.

BACKGROUND: Many patients undergoing hepatectomy for colorectal liver metastases (CRLM) experience recurrence. However, no criteria for screening candidates to undergo repeat hepatectomy (RH) for CRLM have been established. Budding, one form by which colorectal carcinoma malignancies are expressed, is a new pathologic index. This study aimed to analyze prognostic factors, including budding, and to provide criteria for screening candidates to undergo RH for recurrent CRLM. METHODS: Data of 186 consecutive patients who underwent hepatectomy for CRLM between April 2008 and December 2015 were collected. Survival was calculated using the Kaplan-Meier method. Uni- and multivariate analyses were performed to determine factors significantly affecting mortality. RESULTS: Of 186 patients, 131 experienced recurrence after hepatectomy, with 83 of the 131 patients showing recurrence in the liver, and 52 of these 83 patients undergoing primary surgery at the authors' institution and having information on budding grade. In the univariate analysis, preoperative chemotherapy, budding grade, extrahepatic metastases, and number of liver metastases at the time of recurrence were associated with overall survival (OS) for the 52 patients. In the multivariate analysis, budding grade and number of liver metastases at the time of recurrence were associated with OS. CONCLUSION: The study examined simple prognostic factors that could help to screen patients better for RH. Repeat hepatectomy improved the prognosis for patients with recurrent CRLM. The independent prognostic factors for OS were number of liver metastases at recurrence as a conventional factor and budding grade as a new pathologic factor. With budding used as an index, patients who could benefit from hepatectomy can be screened more precisely.

Clinical Significance of Programmed Death Ligand-1 Expression in Esophageal Squamous Cell Carcinoma.

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.

Risk factors for nonalcoholic fatty liver disease after gastrectomy for gastric cancer.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) refers to hepatic steatosis caused by something other than alcoholic liver injury, and often occurs after gastrointestinal surgeries such as pancreatoduodenectomy and gastrectomy. This study aimed to identify the risk factors for NAFLD after gastrectomy for gastric cancer. METHODS: A total of 721 patients who underwent gastrectomy for gastric cancer and plane abdominal computed tomography (CT) preoperatively and 1 year after surgery were included in this study. NAFLD was defined as having a mean hepatic CT attenuation value of < 40 Hounsfield units. We retrospectively examined the relationship between the onset of NAFLD and clinicopathological findings to identify the risk factors associated with the development of NAFLD after gastrectomy. RESULTS: The incidence of postoperative NAFLD was 4.85% (35/721). The univariate analysis identified the following factors as being significantly associated with the incidence of NAFLD: age, preoperative BMI ≥ 25 kg/m2, tumor depth of pT3 ≤, lymph node metastasis grade of pN2 ≤, cholecystectomy, D2 lymphadenectomy, adjuvant chemotherapy, high preoperative cholinesterase serum level, and low grade of preoperative FIB-4 index. Adjuvant chemotherapy (p < 0.001) and high preoperative cholinesterase serum level (p = 0.021) were identified as independent risk factors for NAFLD 1 year after gastrectomy. CONCLUSION: Our study showed that adjuvant chemotherapy with S-1 and high level of serum cholinesterase were considered as the risk factors for NAFLD occurring after gastrectomy for gastric cancer.

Impact of perioperative high mobility group box chromosomal protein 1 expression on long-term outcomes in patients with esophageal squamous cell carcinoma.

BACKGROUND AND AIM: High mobility group box chromosomal protein-1 (HMGB-1) is a potential late mediator of sepsis and a possible risk factor for postoperative pulmonary complications after esophagectomy. This study aimed to determine the relationship between HMGB-1 and clinicopathological factors and long-term prognosis after esophagectomy for esophageal cancer. METHODS: We measured perioperative serum HMGB-1 levels using ELISA and HMGB-1 protein by immunohistochemistry expression in resected specimens. RESULTS: Postoperative serum HMGB-1 levels were significantly higher than preoperative levels. Preoperative serum HMGB-1 levels were significantly higher in patients with more intraoperative bleeding, longer intensive care unit stays, and postoperative pneumonia. Postoperative serum HMGB-1 levels were significantly higher in older patients and those with longer operation time and more intraoperative bleeding. There were significant differences in long-term outcomes according to postoperative but not preoperative serum HMGB-1 levels. Multivariate analysis demonstrated that advanced pathological stage, postoperative pulmonary complications, and higher postoperative serum HMGB-1 levels were independently associated with relapse-free survival and overall survival. Preoperative serum HMGB-1 levels were significantly higher in patients with high HMGB-1 expression than those with low HMGB-1 expression by immunohistochemistry, whereas such statistical differences were not observed in postoperative serum HMGB-1. There were no differences in relapse-free survival and overall survival according to HMGB-1 expression by immunohistochemistry. Serum HMGB-1 levels were significantly increased after esophagectomy for esophageal cancer. CONCLUSION: Elevated postoperative serum HMGB-1, which was associated not only with poor long-term but also short-term outcomes such as postoperative complications, might serve as a potential marker for prognosis in esophageal cancer.

Efficacy of artificial pneumothorax under two-lung ventilation in video-assisted thoracoscopic surgery for esophageal cancer.

BACKGROUND: One-lung ventilation (OLV) is the standard and widely applied ventilation approach used in video-assisted thoracoscopic surgery for esophageal cancer (VATS-e). To address the disadvantages of OLV with respect to difficulties in intubation and induction, as well as the risk of respiratory complications, two-lung ventilation (TLV) with artificial pneumothorax has been introduced for use in VATS-e. However, no studies have yet compared TLV and OLV with postoperative infection and inflammation in the prone position over time postoperatively. Here, we investigated the efficacy of TLV in patients undergoing VATS-e in the prone position. METHODS: Between April 2010 and December 2016, 119 patients underwent VATS-e under OLV or TLV with carbon dioxide insufflation. Clinical characteristics, surgical outcomes, and postoperative outcomes, including oxygenation and systemic inflammatory responses, were compared between patients who underwent OLV and those who underwent TLV. RESULTS: Clinical characteristics other than pT stage were comparable between groups. The TLV group had shorter thoracic operation time than the OLV group. No patients underwent conversion to open thoracotomy. The PaO2/FiO2 ratios of the TLV group on postoperative day (POD) 5 and on POD7 were significantly higher than those of the OLV group. C-reactive protein levels on POD7 were lower in the TLV group than in the OLV group. There were no significant differences with respect to postoperative complications between the OLV and TLV groups. In the TLV group, the white blood cell count on POD7 was significantly lower than that in the OLV group; body temperature showed a similar trend immediately after surgery and on POD1. CONCLUSIONS: In this study, we demonstrated that, compared with OLV, TLV in the prone position provides better oxygenation and reduced inflammation in the postoperative course. Accordingly, TLV might be more useful than OLV for ventilation during esophageal cancer surgery.