Clinical impact of very early recurrence after conversion surgery for stage IV gastric cancer.

Background: The development and improved response to chemotherapy has resulted in a survival benefit of conversion surgery (CS) for advanced gastric cancer (GC). However, this benefit is limited in some cases, such as in those with very early recurrence (VER). This study investigated the relationship between outcome and clinicopathological characteristics after CS for stage IV GC, and the risk factors for VER after CS. Methods: We retrospectively studied 184 patients with stage IV GC who initially underwent chemotherapy, including 36 patients who underwent CS between May 2007 and January 2022. We evaluated the long-term outcome after CS for stage IV GC and the clinicopathological characteristics of the patients who underwent CS. Results: Median survival times (MSTs) in the chemotherapy alone and CS groups were 13.4 and 36.5 months, respectively (p < 0.0001). Of the 27 patients who underwent R0 resection, 22 remained free of early recurrence and five experienced VER. MSTs in the VER and free of early recurrence groups were 15.2 and 44.1 months, respectively (p < 0.0001). Significantly more patients had liver metastasis before initial treatment in the VER group than in the FER group (p = 0.016). There were more patients with preoperative PNI <40 in the VER group (p = 0.046). Conclusion: CS is an effective treatment for stage IV GC, but VER is associated with poor prognosis. We need to carefully consider the indications for CS, especially for patients with poor nutritional status and liver metastases.

Conversion surgery for stage IV gastric cancer with multiple liver metastases with a complete pathological response to S-1 plus oxaliplatin therapy.

Although patients with stage IV gastric cancer who respond well to systemic chemotherapy can be treated with gastrectomy, the prognosis of patients with multiple liver metastases is poor. We herein describe a patient with stage IV gastric cancer with multiple liver metastases who underwent conversion surgery after systemic treatment with S-1 plus oxaliplatin. The patient was a 62-year-old man. Upper gastrointestinal endoscopy revealed a 30-mm type 2 tumor in the greater curvature of the stomach at the anterior wall, and biopsy revealed a poorly differentiated adenocarcinoma. Imaging showed three suspected liver metastases in liver segment S8. The patient was judged to have gastric cancer, cStage IV (cT3N1M1(H)), and systemic chemotherapy was administered. He was treated with a total of six courses of chemotherapy. After re-evaluation, the primary tumor had shrunk significantly, and liver metastases could not be detected. Confirming no signs of seeding by laparoscopy, robot-assisted pylorus-preserving gastrectomy with D2 dissection and laparoscopic partial hepatic (S8) resection were performed. The patient was diagnosed with a complete pathological response. Conversion surgery is an option for stage IV gastric cancer when distant metastases are controlled with chemotherapy and when R0 resection is possible.

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.

Mesothelial cells with mesenchymal features enhance peritoneal dissemination by forming a protumorigenic microenvironment.

Malignant ascites accompanied by peritoneal dissemination contain various factors and cell populations as well as cancer cells; however, how the tumor microenvironment is shaped in ascites remains unclear. Single-cell proteomic profiling and a comprehensive proteomic analysis are conducted to comprehensively characterize malignant ascites. Here, we find defects in immune effectors along with immunosuppressive cell accumulation in ascites of patients with gastric cancer (GC) and identify five distinct subpopulations of CD45(-)/EpCAM(-) cells. Mesothelial cells with mesenchymal features in CD45(-)/EpCAM(-) cells are the predominant source of chemokines involved in immunosuppressive myeloid cell (IMC) recruitment. Moreover, mesothelial-mesenchymal transition (MMT)-induced mesothelial cells strongly express extracellular matrix (ECM)-related genes, including tenascin-C (TNC), enhancing metastatic colonization. These findings highlight the definite roles of the mesenchymal cell population in the development of a protumorigenic microenvironment to promote peritoneal dissemination.

The 5-factor modified frailty index is a novel predictive marker of death from other diseases after curative gastrectomy for gastric cancer.

AIM: The 5-factor modified frailty index (MFI-5) is a stratification tool to evaluate a patient's frailty. This study determined whether the MFI-5 is associated with short- and long-term outcomes after curative gastrectomy in patients with gastric cancer. METHODS: We retrospectively reviewed 447 consecutive patients who underwent curative gastrectomy, and evaluated their overall survival (OS), relapse-free survival (RFS) and cancer-specific survival. RESULTS: A total of 75 patients (16.8%) had high MFI-5 scores (MFI-5 ≥3). A high MFI-5 score was significantly associated with advanced age, male sex and severe postoperative complications. Patients with high MFI-5 scores had significantly poorer OS and RFS than those with low MFI-5 scores (5-year OS, 80.3% vs 59.7%, P < 0.01; 5-year RFS, 77.4% vs 54.9%, P < 0.01). Additionally, a high MFI-5 score was an independent predictor for OS (hazard ratio 1.69, 95% CI 1.09-2.61; P = 0.02) and RFS (hazard ratio, 1.80, 95% CI 1.19-2.74; P = 0.01). However, cancer-specific survival was not significantly different between the two groups. CONCLUSIONS: The MFI-5 score can be predictive of postoperative morbidity and deaths from other disease after curative gastrectomy after curative gastrectomy for gastric cancer. Geriatr Gerontol Int 2023; 23: 750-756.

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.

Relationship between gut microbiome Fusobacterium nucleatum and LINE-1 methylation level in esophageal cancer.

BACKGROUND: We previously demonstrated the relationship of human microbiome Fusobacterium nucleatum with unfavorable clinical outcomes and inferior chemotherapeutic responses in esophageal cancer. Global DNA methylation is associated with the occurrence and development of various cancers. In our previous study, LINE-1 hypomethylation (i.e., global DNA hypomethylation) was associated with a poor prognosis in esophageal cancer. As the gut microbiota may play crucial roles in the DNA methylation of host cells, we hypothesized that F. nucleatum might influence LINE-1 methylation levels in esophageal cancer. METHODS: We qualified the F. nucleatum DNA using a quantitative PCR assay and LINE-1 methylation via a pyrosequencing assay using formalin-fixed paraffin-embedded specimens from 306 esophageal cancer patients. RESULTS: Intratumoral F. nucleatum DNA was detected in 65 cases (21.2%). The LINE-1 methylation scores ranged from 26.9 to 91.8 (median = 64.8) in tumors. F. nucleatum DNA was related to the LINE-1 hypomethylation of tumor lesions in esophageal cancer (P < 0.0001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.71 for F. nucleatum positivity. Finally, we found that the impact of F. nucleatum on clinical outcomes was not modified by LINE-1 hypomethylation (P for interaction = 0.34). CONCLUSIONS: F. nucleatum alters genome-wide methylation levels in cancer cells, which may be one of the mechanisms by which F. nucleatum affects the malignant behavior of esophageal cancer.

The colon inflammatory index score can predict the survival outcome after resection of colorectal cancer: a retrospective multicentre study.

PURPOSE: Many systemic inflammatory markers have been identified to be prognostic factors in various diseases, including colorectal cancer (CRC). The Colon Inflammatory Index (CII), which is based on the lactate dehydrogenase (LDH) level and the neutrophil-to-lymphocyte ratio (NLR), is reportedly a predictor of the outcome of chemotherapy in patients with metastatic CRC. This retrospective review study aimed to determine whether CII can predict the prognosis after surgical resection of CRC. METHODS: A total of 1,273 patients who underwent CRC resection were enrolled and divided into a training cohort (n = 799) and a validation cohort (n = 474). The impact of the preoperative CII score on overall survival (OS) and recurrence-free survival (RFS) was assessed. RESULTS: In the training cohort, the CII score was good in 569 patients (71.2%), intermediate in 209 (26.2%), and poor in 21 (2.6%). There were significant between-group differences in body mass index, American Society of Anaesthesiologists physical status, and preoperative tumour markers. The 5-year OS rate was significantly lower in patients with an intermediate or poor CII score (CII risk) than in those with no CII risk (73.8% vs. 84.2%; p < 0.001, log-rank test). In multivariate analysis, CII risk remained a significant independent predictor of poor OS (hazard ratio 1.75; 95% confidence interval 1.18-2.60; p = 0.006). In the validation cohort, the 5-year OS rate was significantly lower in patients with CII risk than in those with no CII risk (82.8% vs. 88.4%; p = 0.046, log-rank test). CONCLUSION: These findings indicate that the CII can predict OS after resection of CRC.

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.

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.

Stromal Reprogramming through Dual PDGFRα/ß Blockade Boosts the Efficacy of Anti-PD-1 Immunotherapy in Fibrotic Tumors.

Excess stroma and cancer-associated fibroblasts (CAF) enhance cancer progression and facilitate immune evasion. Insights into the mechanisms by which the stroma manipulates the immune microenvironment could help improve cancer treatment. Here, we aimed to elucidate potential approaches for stromal reprogramming and improved cancer immunotherapy. Platelet-derived growth factor C (PDGFC) and D expression were significantly associated with a poor prognosis in patients with gastric cancer, and PDGF receptor beta (PDGFRß) was predominantly expressed in diffuse-type gastric cancer stroma. CAFs stimulated with PDGFs exhibited markedly increased expression of CXCL1, CXCL3, CXCL5, and CXCL8, which are involved in polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) recruitment. Fibrotic gastric cancer xenograft tumors exhibited increased PMN-MDSC accumulation and decreased lymphocyte infiltration, as well as resistance to anti-PD-1. Single-cell RNA sequencing and spatial transcriptomics revealed that PDGFRα/ß blockade reversed the immunosuppressive microenvironment through stromal modification. Finally, combining PDGFRα/ß blockade and anti-PD-1 treatment synergistically suppressed the growth of fibrotic tumors. These findings highlight the impact of stromal reprogramming on immune reactivation and the potential for combined immunotherapy for patients with fibrotic cancer. SIGNIFICANCE: Stromal targeting with PDGFRα/ß dual blockade reverses the immunosuppressive microenvironment and enhances the efficacy of immune checkpoint inhibitors in fibrotic cancer. See related commentary by Tauriello, p. 655.

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.

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.

Successful Management of Anal Squamous Cell Carcinoma With Liver and Ovary Metastases: A Case Report.

BACKGROUND/AIM: Chemoradiation is the recommended initial treatment for locally advanced squamous anal cancer. However, there is still no consensus on the course of treatment for anal canal cancer with distant metastasis, and the significance of surgical resection of distant metastases is also unclear. CASE REPORT: A 48-year-old woman presented to the referral hospital complaining of prolonged bleeding for the past 6 months. On examination, a mass was identified in the anal canal and the upper part of the rectum that was diagnosed as squamous cell carcinoma. Liver, ovarian, and right internal iliac lymph node metastases were found on further examination, and the patient was referred to our department for treatment. Systemic chemotherapy was planned, and six courses of modified FOLFOX6 were administered. After chemotherapy, the liver and right internal iliac lymph node metastases tended to shrink, and no new lesions appeared. Therefore, a total posterior pelvic resection and a bilateral lymph node dissection were performed for the primary tumour and ovarian metastases, and a simultaneous laparoscopic right partial hepatectomy was undertaken for the liver metastases. R0 resection was achieved, and the final diagnosis was T3N3M1a(H) stage IV. The patient remains alive 2 years after the surgery without recurrence. CONCLUSION: We report a rare case of anal canal cancer with distant metastases who achieved R0 resection after modified FOLFOX6 chemotherapy.

Surgical removal of giant pelvic liposarcoma after preoperative transcatheter arterial embolization.

Liposarcoma includes tumors with a wide range of malignancies, from mostly benign to malignant. We report a case of a 73 year-old man who was admitted for urination and defecation disorder. Contract computed tomography (CT) revealed a mass of approximately 21 cm occupying the pelvis, bladder, ureter, prostate, and rectum being compressed by the tumor. Since intraoperative mass bleeding was predicted, we embolized the tumor nutrition artery and performed a total pelvic exenteration. Regarding the course of the operation, SSI and pelvic infection were developed after the operation. The patient was discharged 21 days after surgery. Moreover, there is no evidence of local recurrence and distant metastasis at 18 months after surgery. Furthermore, in giant pelvic liposarcoma, it is useful to identify a nutritional artery of a giant tumor by angiography before surgery, and surgical resection can be safely done by performing preoperative transcatheter arterial embolization.

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.

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.