Body Composition and Clinical Outcomes in Esophageal Cancer Patients Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Obesity is associated with increased mortality in various cancers, but the relationship between obesity and clinical outcomes in unresectable or recurrent esophageal cancer who receive immune checkpoint inhibitors (ICIs) remains unknown. This study investigated the association between body composition and clinical outcomes in patients with unresectable or recurrent esophageal cancer who received ICIs. METHODS: Utilizing an unbiased database of 111 unresectable or recurrent esophageal cancers, we evaluated the relationships between body composition (body mass index, waist circumference, psoas major muscle volume, and subcutaneous and visceral fat areas) at the initiation of ICI treatment and clinical outcomes including the disease control rate and progression-free survival (PFS). RESULTS: Waist circumference was significantly associated with the disease control rate at the first assessment (P = 0.0008). A high waist circumference was significantly associated with favorable PFS in patients treated with nivolumab. In an univariable model, for 5-cm increase of waist circumference in the outcome category of PFS, univariable hazard ratio (HR) was 0.73 (95% confidence interval [CI], 0.61-0.87; P = 0.0002). A multivariable model controlling for potential confounders yielded a similar finding (multivariable HR, 0.56; 95% CI, 0.33-0.94; P = 0.027). We observed the similar finding in esophageal cancer patients treated with pembrolizumab+CDDP+5-FU (P = 0.048). In addition, waist circumference was significantly associated with the prognostic nutritional index (P = 0.0073). CONCLUSIONS: A high waist circumference was associated with favorable clinical outcomes in ICI-treated patients with unresectable or recurrent esophageal cancer, providing a platform for further investigations on the relationships among body composition, nutrition, and the immune status.

Equal short-term outcomes of intracorporeal mechanical gastrogastrostomy in laparoscopic pylorus-preserving gastrectomy for cT1N0 gastric cancer in the middle stomach compared with the extracorporeal hand-sewing method.

BACKGROUND: Intracorporeal mechanical gastrogastrostomy (IMG) techniques have recently been developed and their short-term safety was presented in their initial evaluation. However, whether they are comparable to extracorporeal hand-sewing gastrogastrostomy (EHG) remains unclear. The aim of the study is to establish the safety of IMG in totally laparoscopic pylorus-preserving gastrectomy (TLPPG) compared to EHG in laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG). METHODS: We retrospectively analyzed the short-term outcomes of patients with middle-third early gastric cancer who underwent LAPPG or TLPPG between 2005 and 2022. The primary objective of this study was to evaluate the non-inferiority of IMG to EHG in terms of safety, with the primary endpoint being the risk difference in anastomosis-related complications (ARCs). The sample size required to achieve a statistical power of 80% for the non-inferiority test was 971 with a one-sided alpha level of 5% and non-inferiority of 5%. RESULTS: The analysis included a total of 1,021 patients who underwent LAPPG or TLPPG during the study period. Among them, 488 patients underwent EHG, while 533 underwent IMG. The incidences of ARCs were 11.3% and 11.4% in EHG and IMG, respectively. The observed difference in incidence was 0.0017 (90% confidence interval - 0.0313 to 0.0345), which statistically demonstrated the non-inferiority of IMG to EHG in the incidence of ARCs. Among other complications, the incidence of wound infection in IMG was lower than that in EHG. CONCLUSION: IMG is safe regarding ARCs compared with EHG. These results will encourage surgeons to introduce IMG for patients with early middle gastric cancer.

Intratumour Fusobacterium nucleatum and immune response to oesophageal cancer.

BACKGROUND: Experimental evidence suggests a role of intratumour Fusobacterium nucleatum in the aggressive behaviour of gastrointestinal cancer through downregulating anti-tumour immunity. We investigated the relationship between intratumour F. nucleatum and immune response to oesophageal cancer. METHODS: Utilising an unbiased database of 300 resected oesophageal cancers, we measured F. nucleatum DNA in tumour tissue using a quantitative polymerase chain reaction assay, and evaluated the relationship between the abundance of F. nucleatum and the densities of T cells (CD8 + , FOXP3 + and PDCD1 + ), as well as lymphocytic reaction patterns (follicle lymphocytic reaction, peritumoural lymphocytic reaction, stromal lymphocytic reaction and tumour-infiltrating lymphocytes) in oesophageal carcinoma tissue. RESULTS: F. nucleatum was significantly and inversely associated only with the peritumoural lymphocytic reaction (P = 0.0002). Compared with the F. nucleatum-absent group, the F. nucleatum-high group showed a much lower level of the peritumoural lymphocytic reaction (univariable odds ratio, 0.33; 95% confidence interval, 0.16-0.65; P = 0.0004). A multivariable model yielded a similar finding (multivariable odds ratio, 0.34; 95% confidence interval 0.16-0.69; P = 0.002). CONCLUSIONS: Intratumour F. nucleatum is associated with a diminished peritumoural lymphocytic reaction, providing a platform for further investigations on the potential interactive roles between intratumour F. nucleatum and host immunity.

Frailty Assessed by the Clinical Frailty Scale is Associated with Prognosis After Esophagectomy.

BACKGROUND: The Clinical Frailty Scale (CFS) is a simple and validated tool for assessing frailty, and higher CFS scores are correlated with worse perioperative outcomes after cardiovascular surgery. However, the relationship between the CFS scores and postoperative outcomes after esophagectomy remain unclear. METHODS: We retrospectively analyzed data from 561 patients with esophageal cancer (EC) who underwent resection from August 2010 to August 2020. We defined a CFS score of ≥4 as indicative of frailty; thus, patients were classified into frail patients (CFS scores of ≥4) and non-frail patients (CFS scores of ≤3). The Kaplan-Meier method was used to describe the overall survival (OS) distributions with the log-rank test. RESULTS: Of the 561 patients, 90 (16%) had frailty and 471 (84%) did not. Frail patients had a significantly older age, lower body mass index, higher American Society of Anesthesiologists physical status classification, and greater cancer progression than non-frail patients. The 5-year survival rate was 68% in non-frail patients and 52% in frail patients. OS was significantly shorter in frail than non-frail patients (p = 0.017 by log-rank test). In particular, OS was significantly shorter in frail patients with clinical stage I-II EC (p = 0.0024 by log-rank test) but was not correlated with frailty in patients with clinical stage III-IV EC (p = 0.87 by log-rank test). CONCLUSIONS: Preoperative frailty was associated with shorter OS after resection of EC. The CFS score may be a prognostic biomarker for patients with EC, especially early-stage EC.

C-Reactive Protein Levels After Esophagectomy are Associated with Increased Surgical Complications and Poor Prognosis in Esophageal Squamous Cell Carcinoma Patients.

BACKGROUND: C-reactive protein (CRP) levels are reported to predict complications and survival after surgery in various cancers. However, the relationship between postoperative CRP levels and short- and long-term outcomes of esophageal squamous cell carcinoma (ESCC) patients after esophagectomy is unclear. METHOD: We reviewed the records of 543 ESCC patients who underwent subtotal esophagectomy with gastric conduit reconstruction at Kumamoto University Hospital between August 2010 and July 2021. Blood tests for CRP were done on postoperative days (PODs) 1, 3, 5 or 6, and 7 or 8. RESULTS: The mean CRP levels on day 1, day 3, day 5/6, and day 7/8 were 6.68 ± 0.13 mg/dL, 11.49 ± 0.27 mg/dL, 7.48 ± 0.26 mg/dL, and 5.38 ± 0.22 mg/dL, respectively. Mean CRP levels were highest on day 3, and CRP levels after day 3 correlated with grade >2 complications based on the Clavien-Dindo classification. Receiver operating characteristic curve analysis established the optimal cut-off value for CRP day 3 levels to be 12.19 mg/dL. Multivariate logistic regression analyses found that high CRP day 3 levels significantly correlated with grade >2 complications (odds ratio [OR] 3.77, 95% confidence interval [CI] 2.56-5.35; p < 0.001). Moreover, high day 7/8 CRP levels (>3.52) correlated with postoperative survival, and based on multivariate logistic regression analyses, were significantly associated with poor prognosis (hazard ratio 1.67, 95% CI 1.14-2.43; p = 0.008). CONCLUSION: Our findings suggest CRP day 3 levels as a potential biomarker for predicting postoperative complications and that CRP day 7/8 levels have potential prognostic value for ESCC patients after esophagectomy.

Dynamic Alteration in HLA-E Expression and Soluble HLA-E via Interaction with Natural Killer Cells in Gastric Cancer.

BACKGROUND: Some reports showed the immune tolerance of soluble human leukocyte antigen E (HLA-E), but the role that soluble HLA-E plays in gastric cancer (GC) is unknown. We aimed to clarify the molecular mechanism and clinical significance of soluble HLA-E in GC. METHODS: We examined the expression of HLA-E on GC cells and soluble HLA-E under co-culture with natural killer (NK) cells in a time-dependent manner. Changes in NK cell activity were investigated using anti-NK group 2 member A (NKG2A) antibodies in the presence of soluble HLA-E. Expression of soluble HLA-E in the serum of GC patients was determined. RESULTS: Whereas HLA-E expression on GC cells peaked with interferon (IFN)-γ secretion by NK cells in a time-dependent manner, soluble HLA-E was upregulated in conditioned medium. Pre-incubation with anti-NKG2A antibodies increased the activation of NKG2A+ NK cells in the presence of soluble HLA-E. Expression of soluble HLA-E in the serum of GC patients correlated with disease progression. CONCLUSIONS: HLA-E expression dynamically changes on GC cells and in conditioned medium. Furthermore, soluble HLA-E can contribute to immune escape in GC cell lines, which may have significance in clinical practice. Moreover, soluble HLA-E may be a potential prognostic biomarker.

IL-1ß derived from mixed-polarized macrophages activates fibroblasts and synergistically forms a cancer-promoting microenvironment.

BACKGROUND: Remodeling the tumor microenvironment (TME) to benefit cancer cells is crucial for tumor progression. Although diffuse-type gastric cancer (DGC) preferentially interacts with the TME, the precise mechanism of the complicated network remains unknown. This study aimed to investigate the mutual activation mechanism underlying DGC progression. METHODS: Mass cytometry analysis of co-cultured macrophages, noncancerous fibroblasts (NFs), and DGC cells was performed. RNA sequencing was applied to examine gene expression in fibroblasts. DGC cells were treated with cytokines to examine their effect on characteristic changes. The TCGA and Kumamoto University cohorts were used to evaluate the clinical relevance of the in vitro findings. RESULTS: Cohort analysis revealed that DGC patients had a poor prognosis. The fibroblasts and macrophages interacted with DGC cells to form a cell cluster in the invasive front of DGC tissue. The original 3D triple co-culture system determined the promotional effects of nonmalignant cells on DGC invasive growth. We notably identified a mixed-polarized macrophage cell type with M1/M2 cell surface markers in a triple co-culture system. IL-1ß from mixed-polarized macrophages induced the conversion of NFs to cancer-associated fibroblast-like (CAF-like) cells, promoting the malignant phenotype of DGC cells by inducing the secretion of IL-6, IL-24, and leukemia inhibitory factor (LIF). Moreover, IL-6 and colony stimulating factor 2 (GM-CSF) cooperated to maintain the stable state of mixed-polarized macrophages. Finally, we found that mixed-polarized macrophages were frequently detected in DGC tissues. CONCLUSION: These findings demonstrated that mixed-polarized macrophages exist as a novel subtype through the reciprocal interaction between DGC cells and nonmalignant cells.

Postoperative respiratory morbidity can adversely affect prognosis in thoracoscopic esophagectomy for esophageal cancer: a retrospective study.

BACKGROUND: Esophagectomy for esophageal cancer is associated with frequent respiratory morbidities, which may deteriorate postoperative survival outcomes. Thoracoscopic esophagectomy (TE) is less invasive and is associated with fewer respiratory morbidities than open esophagectomy. However, the relationship between post-TE respiratory morbidity and prognosis has not been well established. METHODS: This study included 378 patients who underwent TE for esophageal cancer between May 2011 and November 2020. Patients were divided into two groups based on the presence of respiratory morbidity. Short-term and long-term outcomes of the groups were retrospectively compared. RESULTS: Respiratory morbidity was significantly associated with heavy past smoking habits (Brinkman index, p = 0.0039), short duration of smoking cessation (p = 0.0012), worse American Society of Anesthesiologists physical status (p = 0.016), frequent cardiovascular comorbidities (p = 0.0085), and long hospital stay (p < 0.001). Respiratory morbidity significantly deteriorated overall survival (OS) (p = 0.011) and relapse-free survival (p = 0.062) and could be an independent prognostic factor for OS (hazard ratio = 1.90, 95% confidence interval = 1.093-3.311, p = 0.023) along with clinical stage. CONCLUSION: Respiratory morbidity can adversely affect prognosis after TE. Various prophylaxes for respiratory morbidity are required to improve the short-term and long-term outcomes of TE for esophageal cancer.

Textbook outcome contributes to long-term prognosis in older adults with gastric cancer.

PURPOSE: Textbook outcome (TO) is a composite quality measurement of short-term outcomes for evaluating surgical procedures. We investigated whether TO can be used to predict outcomes after curative gastric cancer (GC) surgery in older adults. METHODS: We retrospectively analyzed 492 consecutive patients who underwent curative gastrectomy for GC from 2005 to 2017. Among these, 141 advanced-age patients were eligible. The patients were divided into two groups: those who achieved TO (a-TO group) and those who failed to achieve TO (f-TO group). In accordance with previous reports, TO consisted of eight metrics. We evaluated the association between TO and long-term survival. RESULTS: TO was achieved 73 (52%) patients. The patients in the f-TO group had a significantly higher body mass index (P = 0.01), longer surgery time (P = 0.03), and more blood loss (P = 0.001). The metric with the lowest achievement rate was "no postoperative severe complication." The patients in the f-TO group had significantly shorter overall survival than those in the a-TO group (P = 0.03). Multivariable Cox regression analyses of overall survival revealed that an American Society of Anesthesiologists physical status classification of 3 (hazard ratio [HR], 3.28; 95% confidence interval [CI], 1.79-5.98; P < 0.0001) and f-TO (HR, 1.92; 95% CI, 1.09-3.39; P = 0.02) were significantly associated with poor overall survival. CONCLUSION: TO can be used to predict outcomes after curative GC surgery in patients of advanced age.

Textbook outcome contributes to long-term prognosis in elderly colorectal cancer patients.

PURPOSE: Textbook outcome (TO) has been used to define achievement of multiple "ideal" or "optimal" surgical and postoperative quality measures from the patient's perspective. However, TO has not been reported for their impact on survival in elderly, including CRC surgery. This study determined whether TO is associated with long-term outcomes after curative colorectomy in patients with colorectal cancer (CRC). METHODS: Patient who underwent curative surgery over 75 years old for CRC between March 2005 and December 2016. TO included five separate parameters: surgery within 6 weeks, radical resection, Lymph node (LN) yield ≥ 12, no stoma, and no adverse outcome. When all 5 short-term quality of care parameters were realized, TO was achieved (TO). If any one of the 5 parameters was not met, the treatment was not considered TO (nTO). RESULTS: TO was realized in 80 patients (43.0%). Differences in surgical-related characteristics and pathological characteristics according to TO had no statistically significant differences in baseline characteristics, except for Lymph node dissection. The Kaplan-Meier curves for OS and RFS association between TO and nTO had significantly poor 5-year OS and 5-year RFS compared with the TO groups (OS, 77.8% vs. 60.8%, P < 0.01; RFS, 69.6% vs. 50.8%, P = 0.01). In the multivariate analysis, nTO was an independent predictive factor for worse OS (HR, 2.04; 95% confidence interval (CI), 1.175-3.557; P = 0.01) and RFS (HR, 1.72; 95% CI, 1.043-2.842; P = 0.03). CONCLUSIONS: TO can be a useful predictor for postoperative morbidity and prognosis after curative colorectomy for CRC.

Prognostic value of 18F-fluorodeoxyglucose uptake in the bone marrow on pretreatment positron emission tomography/computed tomography in patients with esophageal cancer who underwent esophagectomy.

BACKGROUND: Increased 18F-fluorodeoxyglucose (FDG) uptake in the bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) clinically reflects increased BM metabolism owing to systemic inflammation, bacterial infection, anemia, and cytokine-producing tumors. The association between FDG uptake in the BM and prognosis after esophagectomy for esophageal cancer has not been investigated. METHODS: This study included 651 patients who underwent PET/CT before any treatment and McKeown esophagectomy for esophageal cancer between June 2007 and August 2021. The pretreatment degree of FDG uptake in the BM was evaluated using a visual assessment criterion. Patients were divided into low- and high-FDG uptake groups. We retrospectively investigated whether the degree of FDG uptake in the BM was associated with clinicopathological and surgical backgrounds, blood parameters, and prognosis. RESULTS: High FDG uptake in the BM was significantly associated with elevated white blood cell and neutrophil counts, increased C-reactive protein levels, decreased hemoglobin, serum albumin, and total cholesterol levels. High FDG uptake in the BM was an independent predictor of worse overall survival in clinical stages 0-II esophageal cancer (hazard ratio, 2.27; 95% confidence interval, 1.097-4.695; P = 0.027). Worse overall survival was also associated with advanced age, low American Society of Anesthesiologists physical status, an advanced clinical stage, and high intraoperative blood loss. CONCLUSION: Increased FDG uptake in the BM on pretreatment PET/CT may be a surrogate indicator of various clinically disadvantageous backgrounds and may act as a predictor of poor prognosis after esophageal cancer surgery.

Comprehensive Analysis of Multiple Primary Cancers in Patients With Esophageal Squamous Cell Carcinoma Undergoing Esophagectomy.

OBJECTIVE: The aim of this study was to elucidate the latest epidemiology and risk factors for multiple primary cancers (MPCs), and the association between neoadjuvant chemotherapy (NAC) and postoperative metachronous cancer (PMC) in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy. SUMMARY OF BACKGROUND DATA: Background data to derive appropriate screening strategies are insufficient. METHODS: This study consisted of 3 retrospective investigations. A total of 766 consecutive patients with ESCC who underwent esophagectomy between April 2005 and December 2019 were eligible for epidemiological analysis. Of these, 688 patients without missing data were analyzed for the risk of MPCs. In total, 364 patients who underwent NAC (115) and no preoperative treatments (249) were investigated for the association between NAC and PMC. RESULTS: Of 766 patients, 288 (38%) patients experienced 357 MPCs in their life. PMCs identified after the completion of 5-year postoperative follow-up were significantly more advanced (P = 0.019). Male sex [hazard ratio (HR) = 3.04, P = 0.038], older age (HR = 2.39, P < 0.001), and diabetes mellitus (HR = 1.76, P = 0.034) were risk factors for preoperative metachronous cancers. Heavy smoking (HR = 1.70, P = 0.014) and drinking (HR = 1.61, P = 0.029) were risk factors for synchronous cancers. NAC significantly reduced PMC incidence ( P = 0.043). NAC showed a trend to contribute to improved survival via reduced deaths from PMCs, although this did not reach significance ( P = 0.082). CONCLUSIONS: ESCC is associated with a high risk of MPCs. Continuing follow-up for PMCs after the completion of 5-year postoperative follow-up is important. NAC may reduce PMCs, representing a novel mechanism for improving survival in patients with locally advanced ESCC.

Clinical Significance of Pretreatment Red Blood Cell Distribution Width as a Predictive Marker for Postoperative Morbidity After Esophagectomy for Esophageal Cancer: A Retrospective Study.

BACKGROUND: Clinical significance of red blood cell distribution (RDW) as a predictive marker for the incidence of postoperative morbidity after esophagectomy for esophageal cancer has not been established. METHODS: This study included 634 consecutive patients who underwent three-incisional esophagectomy with lymphadenectomy for esophageal cancer between April 2005 and November 2020. Correlation between pretreatment RDW and patient background, cancer background, and short-term outcome after esophagectomy were retrospectively investigated. RESULTS: Eighty patients (12.6%) had a high pretreatment RDW (> 14.2), which correlated with malnutrition estimated by body mass index, hemoglobin, total lymphocyte count, albumin, and total cholesterol. High pretreatment RDW was an independent risk factor for postoperative severe morbidity of grade IIIb or higher based on the Clavien-Dindo classification (hazard ratio [HR] 3.90, 95% confidence interval [CI] 1.707-8.887; p = 0.0012) and reoperation (HR 4.39, 95% CI 1.552-12.390; p = 0.0053) after open esophagectomy (OE). However, RDW was not associated with postoperative morbidity incidence after minimally invasive esophagectomy (MIE). CONCLUSIONS: Pretreatment RDW may be a surrogate marker for nutritional status and could be a predictive marker for postoperative severe morbidity, reoperation, and possibly pneumonia after OE. On the contrary, the lower invasiveness of MIE may have reduced the effect of pretreatment malnutrition on morbidity incidence, which could explain the insignificant relationship between RDW and poor short-term outcomes in MIE.

Preoperative Smoking Cessation and Prognosis After Curative Esophagectomy for Esophageal Cancer: A Cross-Sectional Study.

BACKGROUND: Several cohort studies have reported that post-esophagectomy morbidities may worsen prognosis. Smoking cessation is an effective prophylactic measure for reducing post-esophagectomy morbidity; however, whether smoking cessation can contribute to the improvement of prognosis is unknown due to the absence of reliable databases covering the cessation period. This study aimed to elucidate whether sufficient preoperative smoking cessation can improve prognosis after esophageal cancer surgery by reducing post-esophagectomy morbidity. METHODS: This study included 544 consecutive patients who underwent curative McKeown and Ivor-Lewis esophagectomies for esophageal cancer between May 2011 and June 2021. Data on smoking status and cessation period were prospectively accumulated. Survival data were finally updated on 30 January 2022. Receiver operating characteristic curve analysis for the cut-off value of appropriate cessation period in reducing post-esophagectomy respiratory morbidity as well as analyses for the association of cessation period with short- and long-term outcomes were performed. RESULTS: Post-esophagectomy morbidity significantly diminished overall survival (OS) after esophagectomy (p = 0.0003). A short preoperative smoking cessation period of ≤ 2 months was associated with frequent post-esophagectomy morbidity of Clavien-Dindo classification ≥IIIb (p = 0.0059), pneumonia (p = 0.016), respiratory morbidity (p = 0.0057), and poor OS in clinical stages II and III (p = 0.0015). Moreover, it was an independent factor for poor OS (hazard ratio 1.85, 95% confidence interval 1.068-3.197; p = 0.028), along with body mass index <18.5 and R1 resection. CONCLUSIONS: Sufficient preoperative smoking cessation > 2 months may be effective in improving not only short-term outcomes but also prognosis after esophagectomy for locally advanced esophageal cancer.

Prophylactic laparoscopic total gastrectomy for gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): the first report in Asia.

A 41-year-old woman was admitted to our hospital for epigastralgia. She had been admitted to another hospital for fundic gland polyposis (FGP) without any symptoms, and no malignancy had been noted in her previous endoscopy. However, a biopsy performed at our hospital revealed adenocarcinoma, and computed tomography (CT) revealed multiple liver and peritoneal metastases. We clinically suspected gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) and indicated genetic testing. The point mutation in exon 1B of APC was revealed. She was diagnosed with GAPPS with multiple liver metastases and underwent systemic chemotherapy. She has two older brothers who also have FGP. The same genomic mutation was observed in both brothers and their mother, and they were also diagnosed with GAPPS. The brothers underwent prophylactic laparoscopic total gastrectomy with D1 lymph-node dissection.

Impact of Type of Gastrectomy on Death from Pneumonia in Elderly Patients with Gastric Cancer Over the Long Term.

BACKGROUND: Gastrectomy may induce significant postoperative disabilities and worsen the quality of life in elderly patients. Without a functioning esophagogastric junction (EGJ), swallowing is impaired because of the anatomical and physiological changes after surgery, which increases the risk of postoperative pneumonia. The aim of this study was to identify the impact of the type of surgical procedure on death from pneumonia in elderly patients with gastric cancer (GC) over the long term. METHODS: We analyzed the data of 343 patients with GC who underwent curative gastrectomy in our hospital. We divided the patients into elderly and non-elderly groups. Among them, 109 patients aged ≥ 75 years who underwent curative resection were analyzed, their clinicopathological factors and clinical outcomes were compared, and the impact of the type of surgical procedure on death from pneumonia over the long term was evaluated. The institutional scientific review board of Kumamoto University Hospital was approved for data collection and analysis (No. 1037). RESULTS: There were significantly higher levels of American Society of Anesthesiologists (ASA) and poor nutrition in the elderly group; however, gender, BMI and factors related to pneumonia did not differ significantly between groups. The median duration of follow-up time 1588 days. On the multivariate analysis, age and surgical procedure were selected as independent predictive factors for pneumonia-related survival. CONCLUSION: Preservation of the EGJ as much as possible while maintaining curability is useful for reducing postoperative death from pneumonia over the long term in elderly patients with gastric cancer.

A retrospective study of preoperative malnutrition based on the Controlling Nutritional Status score as an associated marker for short-term outcomes after open and minimally invasive esophagectomy for esophageal cancer.

PURPOSE: Preoperative malnutrition is a significant risk factor for post-esophagectomy morbidity. The Controlling Nutritional Status (CONUT) is an index used to assess nutritional status, and it has been suggested to predict post-esophagectomy morbidity. However, the difference in the predictive value of CONUT in estimating morbidities between open esophagectomy (OE) and minimally invasive esophagectomy (MIE) has not yet been elucidated. METHODS: This study included patients who underwent a three-incision esophagectomy for esophageal cancer between April 2005 and August 2021. The patients were further divided into two groups according to their preoperative CONUT scores: normal and light malnutrition and moderate and severe malnutrition. Short-term outcomes between these groups were retrospectively compared in the OE and MIE groups. RESULTS: A total of 674 patients who underwent OE (296) and MIE (378) were analyzed. Moreover, 32 patients of the OE group and 16 of the MIE group were classified as having moderate and severe malnutrition, respectively. Moderate and severe malnutrition was significantly associated with a low body mass index, poor performance status, poor American Society of Anesthesiologists physical status, advanced cancer stage, and frequent preoperative treatment. These patients also experienced significantly more frequent morbidities of grade ≥ IIIb according to the Clavien-Dindo classification (CDc), respiratory, and cardiovascular morbidities after OE. Moreover, moderate and severe malnutrition in CONUT was an independent risk factor for morbidity of CDc ≥ IIIb (odds ratio [OR] vs. normal and light malnutrition = 3.38; 95% confidence interval [CI], 1.225-9.332; p = 0.019), respiratory (OR = 3.00; 95% CI, 1.161-7.736; p = 0.023), and cardiovascular morbidities (OR = 3.66; 95% CI, 1.068-12.55; p = 0.039) after OE. Meanwhile, moderate and severe malnutrition in CONUT did not increase the incidence of postoperative morbidities after MIE. CONCLUSION: Preoperative malnutrition in CONUT reflects various disadvantageous clinical factors and could be a predictor of worse short-term outcomes after OE, but it has no value in MIE. The low invasiveness of MIE might reduce the effect of preoperative malnutrition on worse short-term outcomes.

Minimally invasive esophagectomy may contribute to low incidence of postoperative surgical site infection in patients with poor glycemic control.

PURPOSE: High preoperative hemoglobin A1c (HbA1c) levels have been suggested to increase complications after esophagectomy. Minimally invasive esophagectomy (MIE) is less invasive than open esophagectomy (OE) and may reduce postoperative complications. However, it has not been established whether MIE contributes to low morbidity in patients with high preoperative HbA1c levels. Thus, the current study aimed to elucidate the effect of preoperative HbA1c levels on the incidence of complications each after OE and MIE. METHODS: A total of 280 patients who underwent OE and 304 patients who underwent MIE for esophageal cancer between April 2005 and April 2020 were retrospectively analyzed. The OE and MIE groups were further divided into two groups according to their preoperative HbA1c levels (< 6.9%, ≥ 6.9%). RESULTS: Patients with high HbA1c levels had a significantly higher incidence of surgical site infections (SSIs) after OE (P = 0.0048). Multivariate analysis demonstrated that a high HbA1c level was an independent risk factor for frequent SSIs after OE (hazard ratio 2.52; 95% confidence interval, 1.101- 5.739; P = 0.029). On the contrary, a high HbA1c level did not affect the incidence of SSI after MIE (P = 1.00). A high HbA1c level was not associated with the incidence of morbidities other than SSI after OE and MIE. CONCLUSIONS: A high preoperative HbA1c level significantly increased SSI risk after OE but not after MIE. It was suggested that lower invasiveness of MIE could contribute to a low incidence of SSI, even in patients with poor preoperative glycemic control.

Clinicopathological characteristics and prognosis of poorly cohesive cell subtype of gastric cancer.

BACKGROUND: The new World Health Organization (WHO) classification of gastric cancer includes a histological subtype of poorly cohesive carcinoma (PCC), which includes signet-ring cell (SRC) phenotype. We aimed to examine the concordance between preoperative clinical and postoperative histological diagnoses according to the 2010 WHO histological subtypes and to compare the prognoses of these subtypes. METHODS: The study cohort comprised 665 patients who underwent gastrectomy from 2005 to 2019. Histological subtypes were classified into PCC-NOS (non-signet ring cell subtype), SRC, and non-PCC, which were defined by the predominant component in accordance with the 2010 WHO classification of gastric cancer. The concordance of clinical and pathological diagnosis was examined and clinicopathological characteristics and survival outcome of the three subtypes compared. RESULTS: The cancers of 443 patients (66.7%) were classified as non-PCC, of 112 patients (16.8%) as PCC-NOS, and of 110 patients (16.5%) as SRC predominant subtypes. Significant differences in sex, age, tumor location, size, macroscopic type, and pathological TNM category (all P<0.05) were found. The concordance rate of preoperative and postoperative histological subtypes was significantly lower for poorly cohesive than other subtypes (P<0.0001). Preoperative stage tended to be underestimated for PCC-NOS subtype and these patients had poorer overall survival than those with the other two subtypes (P=0.005). Multivariate logistic regression analysis of overall survival showed that WHO histological subtype (PCC-NOS vs. non-PCC/SRC, HR: 1.64, 95% CI: 1.18-2.29, P=0.0034) was a significant independent prognostic factor. CONCLUSION: Our results suggest that poorly cohesive carcinoma subtypes have different biological characteristics and prognoses.

Preoperative transferrin level is a novel indicator of short- and long-term outcomes after esophageal cancer surgery.

BACKGROUND: This study aimed to examine whether preoperative serum transferrin, a rapid-turnover protein, correlates with short- and long-term outcomes after esophagectomy. METHODS: Preoperative transferrin levels, calculated by summing serum iron and unsaturated iron-binding capacity, were evaluated in 224 patients who underwent esophagectomy for stage I-III esophageal cancer without preoperative treatment. Transferrin levels are directly proportional to total iron-binding capacity (TIBC), and we defined TIBC < 250 µg/dL as low transferrin. We evaluated the relationship between preoperative transferrin levels and short- and long-term outcomes after esophagectomy using univariate and multivariate Cox proportional hazards analyses. RESULTS: Of all patients, 25 (11.2%) had low preoperative transferrin levels. Low preoperative transferrin levels were strongly correlated with worse preoperative performance status, advanced pathological T stage, and more open esophagectomy (p = 0.0078, 0.0001, and 0.013, respectively). Patients with low preoperative transferrin levels experienced significantly more frequent postoperative pneumonia in univariate and multivariate analysis [hazard ratio (HR) 3.30, 95% confidence interval (CI) 1.032-10.033, p = 0.0443]. Additionally, these patients were significantly correlated with worse overall survival (OS) in univariate and multivariate analyses (HR 2.75, 95% CI 1.018-7.426, p = 0.0460). Furthermore, we investigated the relationship between OS and postoperative pneumonia to elucidate why low preoperative transferrin, which is an independent risk factor for postoperative pneumonia, leads to poor prognosis. Patients with postoperative pneumonia were strongly associated with a shorter OS (p = 0.0099). CONCLUSION: Preoperative serum transferrin levels may be a novel indicator of postoperative pneumonia and OS after esophagectomy.