Prognostic Impact of Serum SCC Antigen in the 566 Upfront Surgery Group of Esophageal Squamous Cell Carcinoma: A Multi-Institutional Study of the Japan Esophageal Society.

PURPOSE: This study aimed to determine the clinicopathologic and prognostic significance of squamous cell carcinoma antigen (SCC-Ag) in patients with esophageal SCC who underwent radical surgery without neoadjuvant therapy. METHODS: This study included 566 patients with primary esophageal SCC who underwent radical resection without neoadjuvant therapy at 15 Japanese hospitals between 2008 and 2016. The cutoff value of SCC-Ag was 1.5 ng/mL based on the receiver operating characteristic curves. Preoperative SCC-Ag and postoperative SCC-Ag were analyzed to evaluate clinicopathological and prognostic significance. Survival curves were compared between the SCC-Ag-positive group and the SCC-Ag-negative group. The prognostic impact of SCC-Ag was evaluated using univariate and multivariate analyses. RESULTS: The preoperative SCC-Ag-positive rate was 23.5% (133/566). SCC-Ag-positive status was significantly associated with old age (p = 0.042), tumor depth (p <0.001), and tumor stages (p <0.001). The preoperative SCC-Ag-positive group had significantly poorer overall survival than the SCC-Ag-negative group (p = 0.030), but it was not an independent predictor of poor prognosis. Postoperative SCC-Ag-positive status was an independent risk factor for poor overall survival (p = 0.034). CONCLUSION: Both pre- and postoperative SCC-Ag-positive statuses were significantly associated with poor prognosis. Postoperative SCC-Ag-positive status was an independent risk factor for predicting overall survival.

The relationship between the treatment course and prognosis of oligometastasis after esophageal squamous cell carcinoma resection.

PURPOSE: The concept of oligometastasis, which represents limited metastatic disease, has recently gained interest, accompanied by a more detailed classification. This study aims to investigate the relationship between the treatment course and prognosis in patients with a recurrence of esophageal squamous cell carcinoma (ESCC) after curative esophagectomy. METHODS: 126 patients with ESCC recurrence after curative resection were enrolled in this study. Oligometastasis was defined as fewer than five recurrences in a single organ. Patients were classified as having oligometastatic recurrence (OLR) or polymetastatic recurrence (PLR). Patients were further classified into four subgroups according to lesion progression: persistent oligorecurrence (PER-OLR), converted polyrecurrence (CON-PLR), induced oligorecurrence (IND-OLR), and persistent polyrecurrence (PER-PLR). We analyzed the relationship between the recurrence patterns and prognosis according to the progression of oligometastatic lesions. RESULTS: OLR was identified in 58 (46%) of 126 patients with recurrence. Patients with OLR had a significantly better prognosis than those with PLR (P < 0.0001). A further subgroup analysis revealed that patients who underwent IND-OLR had a similar prognosis to those who underwent PER-OLR. CONCLUSIONS: This study suggests that OLR is a prognostic factor after recurrence following resection of ESCC and that PLR can be converted to OLR by therapeutic intervention to achieve a long-term survival.

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.

Extracellular water to total body water ratio, a novel predictor of recurrence in patients with colorectal cancer.

Background: Total body water (TBW) fraction, which accounts for 60% of body weight, is an important indicator of body composition, and the extracellular water to TBW ratio (ECW/TBW) is reportedly useful in predicting clinical outcomes of patients with organ disorders. We aimed to clarify the clinical impact of preoperative ECW/TBW status on survival outcomes in cancer patients. Methods: We used a database of 320 colorectal cancer (CRC) patients who underwent potentially curative resections. Preoperative ECW/TBW was measured using a bioelectrical impedance analysis (BIA), and its correlation with patient survival outcomes, clinicopathological factors, laboratory data, and comorbidities were analyzed. Results: A high preoperative ECW/TBW was significantly associated with poorer relapse-free survival (RFS; p = 0.001) and overall survival (OS; p = 0.003). A high ECW/TBW ratio was significantly associated with older age (p < 0.001), low BMI (p = 0.009), and right-sided tumors (p = 0.03). In a multivariate analysis, a high ECW/TBW significantly predicted a higher RFS mortality (HR: 2.07, 95% CI: 1.10-3.88, p = 0.024) and OS mortality (HR: 3.23, 95% CI: 1.25-8.36, p = 0.016). Furthermore, a high ECW/TBW was significantly associated with lower hemoglobin (p < 0.001) and albumin levels (p < 0.001), but not comorbidities. Conclusions: A high preoperative ECW/TBW was a predictive factor for recurrence and poorer overall survival independent of the tumor, node, and metastasis (TNM) stage. Our data suggest that preoperative evaluation of ECW/TBW using BIA might serve as a novel tool for developing CRC treatment strategies.

Relationship between the severity of emphysematous change in the lung and morbidity after esophagectomy for esophageal cancer: A retrospective study on a novel strategy for risk prediction.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) prevalence increases post-esophagectomy morbidity. However, the association between COPD severity and post-esophagectomy morbidity remains unclear because of the lack of an objective method to classify COPD severity. Low attenuation volume ratio (LAVR) estimated using Ziostation2 may reflect the extent of emphysematous changes in the lungs and COPD severity, thereby predicting post-esophagectomy morbidity. METHODS: A total of 776 patients who underwent curative McKeown esophagectomy for esophageal cancer between April 2005 and June 2021 were included. The patients were divided into high and low preoperative LAVR groups. Short-term outcomes between the groups were compared for patients who underwent open esophagectomy (OE) and minimally invasive esophagectomy (MIE). RESULTS: A total of 219 (28%) patients were classified into the high LAVR group. High LAVR was significantly associated with disadvantageous patient characteristics such as advanced age, heavy smoking, and impaired respiratory function. Patients with high LAVR had a significantly higher incidence of severe morbidity and pneumonia after OE. High LAVR was an independent risk factor for severe morbidity (odds ratio [OR], 2.52; 95% confidence interval [CI]: 1.237-5.143; p = 0.011) and pneumonia (OR, 2.12; 95% CI: 1.003-4.493; p = 0.049) after OE. Meanwhile, LAVR was not correlated with the incidence of post-MIE morbidity. CONCLUSIONS: LAVR may reflect COPD severity and predict severe morbidity and pneumonia after OE, but not after MIE. Less invasiveness of MIE may alleviate the effects of various disadvantageous backgrounds associated with high LAVR on worse short-term outcomes.

LINE-1 hypomethylation, increased retrotransposition and tumor-specific insertion in upper gastrointestinal cancer.

The long interspersed nuclear element-1 (LINE-1) retrotransposons are a major family of mobile genetic elements, comprising approximately 17% of the human genome. The methylation state of LINE-1 is often used as an indicator of global DNA methylation levels and it regulates the retrotransposition and somatic insertion of the genetic element. We have previously reported the significant relationship between LINE-1 hypomethylation and poor prognosis in upper gastrointestinal (GI) cancers. However, the causal relationships between LINE-1 hypomethylation, retrotransposition, and tumor-specific insertion in upper GI cancers remain unknown. We used bisulfite-pyrosequencing and quantitative real-time PCR to verify LINE-1 methylation and copy number in tissue samples of 101 patients with esophageal and 103 patients with gastric cancer. Furthermore, we analyzed the LINE-1 retrotransposition profile with an originally developed L1Hs-seq. In tumor samples, LINE-1 methylation levels were significantly lower than non-tumor controls, while LINE-1 copy numbers were markedly increased. As such, there was a significant inverse correlation between the LINE-1 methylation level and copy number in tumor tissues, with lower LINE-1 methylation levels corresponding to higher LINE-1 copy numbers. Of particular importance is that somatic LINE-1 insertions were more numerous in tumor than normal tissues. Furthermore, we observed that LINE-1 was inserted evenly across all chromosomes, and most often within genomic regions associated with tumor-suppressive genes. LINE-1 hypomethylation in upper GI cancers is related to increased LINE-1 retrotransposition and tumor-specific insertion events, which may collectively contribute to the acquisition of aggressive tumor features through the inactivation of tumor-suppressive genes.

Complete pathologic response after laparoscopic hepatectomy following treatment with nivolumab and ipilimumab for anticancer drug-resistant MSI-high colon cancer liver metastasis consisting of poorly differentiated adenocarcinoma with squamous differentiation: A case report.

A 56-year-old man referred to our hospital for cecum cancer. Enhanced computed tomography (CT) found swollen reginal lymph nodes and liver metastasis. Magnetic Resonance Imaging (MRI) revealed a solitary lesion on liver (S2). We performed a laparoscopic ileocolic resection and liver partial resection. Tumor pathology showed that these tumors were moderate-differentiated adenocarcinoma (pT3N2bM1 Stage IVA). Genetic examination revealed MSI-high, KRAS wild type, and BRAF wild type. After surgery, two liver metastases were found in S4 and S7 as new lesion in EOB-MRI. We started chemotherapy with the FOLFOFIRI plus bevacizumab regimen, but two liver metastases were enlarged after six cycles of chemotherapy. As a second-line treatment, nivolumab and ipilimumab combination therapy was started. After three cycles of these therapy, both of these tumors shrinkage were observed. We performed laparoscopic liver resection. In specimens, there were no malignant cells. Pathological study revealed that in the initial surgery specimen, PD-L1 protein was detected in both primary and metastatic lesions, and HLA-DR, CK5/6 in liver. No recurrence was observed at 6 months after the surgery. In conclusion, we reported the case of anticancer drug-resistant MSI-high colon cancer liver metastasis was resected after treatment with immune-checkpoint inhibitors and a pathological complete response was found.

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.

Repeated intestinal perforations in vascular Ehlers-Danlos syndrome: a case report of a novel mutation in the COL3A1 gene.

BACKGROUND: Ehlers-Danlos syndrome is an inherited connective-tissue disorder characterized by skin hyperextensibility, joint hypermobility, and tissue fragility. Intestinal perforation is one of the fatal manifestations of this syndrome, and its management is complicated. CASE PRESENTATION: A 58-year-old woman with a familial history of Ehlers-Danlos syndrome visited the emergency department due to a sudden onset of lower abdominal pain. Plain abdominal computed tomography showed abdominal free air. We found a perforated descending colon and subsequently resected this lesion and performed ileostomy. Fifty-one days after this first operation, the patient had transverse colon perforation and thus underwent the Hartmann procedure as the second operation. In addition, she was diagnosed with small bowel perforation 53 days after the first operation and consequently underwent a third operation-partial resection of the jejunum with functional end-to-end anastomosis. Fifty-eight days after the first operation, she complained of acute abdominal pain. Plain abdominal computed tomography showed fluid collection near the jejunojejunal anastomosis. We detected dehiscence at the entry hole of the linear stapler during the operation and thus performed partial resection of the affected jejunum, followed by jejunostomy. The postoperative course of the fourth operation was uneventful. Genetic testing revealed a novel missense mutation (c.2095G>T, p.Gly699Cys) in the COL3A1 gene, which is presumed to be a pathogenic variant of vascular Ehlers-Danlos syndrome. CONCLUSION: Vascular Ehlers-Danlos syndrome should be considered in the case of repeated intestinal perforation. The identified missense mutation in the COL3A1 gene (c.2095G>T, p.Gly699Cys) might be a novel pathogenic variation causing vascular Ehlers-Danlos syndrome. Careful postoperative screening and multidisciplinary management are required.

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.

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.

The Geriatric Nutritional Risk Index is a prognostic marker in patients with metastatic colorectal cancer.

BACKGROUND: The Geriatric Nutritional Risk Index (GNRI) is a nutritional index for elderly patients that is associated with prognosis in cancer patients. We investigated using the GNRI in patients with metastatic colorectal cancer to predict prognosis. METHODS: This study included 419 metastatic colorectal cancer patients who received first-line chemotherapy between February 2005 and December 2020. First, we calculated pre-treatment GNRI and divided the patients into four groups according to the values (G1-G4). We evaluated patient characteristics and overall survival in the four groups. RESULTS: Overall, 419 patients were included. The median follow-up was 34.4 months. Lower GNRI was positively associated with a lower grade Eastern Cooperative Oncology Group Performance Status (p = 0.009), synchronous metastases (p < 0.001), primary tumor resection prior to chemotherapy (p = 0.006), and did not undergo resection after chemotherapy (p < 0.001). Patients with low GNRI had significantly shorter overall survival than the group with high GNRI (median OS: G1 = 19.3 months [M], G2 = 30.8 M, G3 = 38 M, G4 = 39.7 M; log-rank test, p < 0.001). Multivariate Cox regression analysis showed that GNRI was an independent prognostic factor (G3: HR = 0.49, 95% CI = 0.35-0.69; G4: HR = 0.67, 95% CI = 0.48-0.93). In the subgroup analysis of overall survival, we found no interaction between clinicopathological factors and the prognostic value of GNRI. Interestingly, younger patients (< 70 years) but not older patients showed a significant difference in overall survival according to GNRI, despite being the metric being designed for elderly patients. CONCLUSION: Pretreatment GNRI can be a prognostic marker for patients with mCRC who received systemic chemotherapy.

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.

Chemically Driven Ion Exchanging Synthesis of Na5YSi4O12-Based Glass-Ceramic Proton Conductors.

We have developed 12-membered silica-tetrahedra-ringed Na5YSi4O12-type sodium ion conducting glass-ceramics on the basis of the composition Na3+3x-yR1-xPySi3-yO9 (R: rare earth elements; denoted as Narpsio); especially, the material of Na4Y0.6P0.2Si2.8O9 with the combined parameters of (x, y) = (0.4, 0.2) gives rise to the maximum conductivity of 1 × 10-1 Scm-1 at 300 °C. Because glass-ceramics generally have the advantage of structural rigidity and chemical durability over sintered polycrystalline ceramics, the present study employed glass-ceramic Narpsio to perform chemically driven ion exchange of Na+ with protonated water molecules with an aim to produce a proton conductor. The ion exchange was carried out in a hydrochloric acid solution by changing immersion time, temperature, and acid concentration. The ion exchanged Na4Y0.6P0.2Si2.8O9-based glass-ceramics were analyzed by the complex impedance method, and the proton conductivity was found to exhibit 3 × 10-4 Scm-1 at 300 °C with the activation energy of 59 kJ/mol. The dependence of humidity-sensitive conductivity of the ion exchanged bulk glass-ceramics was also examined; the conductivity increased almost linearly from 0.6 × 10-4 Scm-1 in dry air to 1.5 × 10-4 Scm-1 in 75% humid ambience at 300 °C. Thus, the ion exchanged glass-ceramics can be considered to be high temperature proton conductors as well as humidity sensors.