Textbook outcome contributes to long-term prognosis in elderly patients with esophageal squamous cell carcinoma.

Purpose: Textbook outcome (TO) is a composite quality measurement of outcomes for evaluating surgical procedures. We investigated whether TO can be used to predict outcomes after curative resection for esophageal squamous cell carcinoma (ESCC) in elderly patients. Methods: We retrospectively analyzed 105 patients who underwent curative esophagectomy for ESCC from 2005 to 2020. In accordance with previous reports, TO consisted of 10 parameters. The patients were divided into two groups: those who achieved TO (TO) and those who failed to achieve TO (non-TO). We evaluated the association between TO and long-term survival. Results: TO was achieved in 28 (26%) patients. The patients in the TO group were significantly older (p = 0.02). The parameter with the lowest achievement rate was "No hospital stay ≥21 days". The patients in non-TO group had significantly shorter overall survival than those in TO group (p = 0.03). Multivariable Cox regression analyses of overall survival revealed that lymph node metastasis (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.73-6.78; p < 0.0002) and non-TO (HR, 2.37; 95% CI, 1.05-5.65; p = 0.03) were significantly associated with poor overall survival. Conclusion: TO can be used to predict outcomes after curative esophagectomy in elderly patients with ESCC.

Esophageal dedifferentiated liposarcoma resected by the cervical approach: a case report.

BACKGROUND: While liposarcomas tend to mainly occur in the soft tissues of the extremities and retroperitoneum, esophageal liposarcoma is rare. Herein, we report a case of a patient who underwent complete resection of an esophageal dedifferentiated liposarcoma via the cervical approach, leading to the preservation of the esophagus. CASE PRESENTATION: A 69-year-old man underwent an upper gastrointestinal endoscopy, as a result of which a submucosal-like tumor was observed. Upper gastrointestinal imaging showed a 12-cm tumor with a stalk arising from the esophageal entrance, extending to the middle intrathoracic esophagus, with a normal surface mucosa. Endoscopic ultrasound-fine needle aspiration biopsy showed that the nuclei of tumors cells were positive for murine double minute (MDM) and weakly positive for cyclin-dependent kinase 4 (CDK4). We diagnosed the tumor as the esophageal dedifferentiated liposarcoma, and planed tumor resection via the cervical approach. The tumor was successfully resected and the postoperative course was uneventful. CONCLUSION: This case report highlights the use of tumor resection via the cervical approach as a good option for esophageal liposarcoma.

Presence of Fusobacterium nucleatum in relation to patient survival and an acidic environment in oesophagogastric junction and gastric cancers.

BACKGROUND: Fusobacterium nucleatum inhabits the oral cavity and affects the progression of gastrointestinal cancer. Our prior findings link F. nucleatum to poor prognosis in oesophageal squamous cell carcinoma via NF-κB pathway. However, its role in oesophagogastric junction and gastric adenocarcinoma remains unexplored. We investigated whether F. nucleatum influences these cancers, highlighting its potential impact. METHODS: Two cohorts of EGJ and gastric adenocarcinoma patients (438 from Japan, 380 from the USA) were studied. F. nucleatum presence was confirmed by qPCR, FISH, and staining. Patient overall survival (OS) was assessed based on F. nucleatum positivity. EGJ and gastric adenocarcinoma cell lines were exposed to F. nucleatum to study molecular and phenotypic effects, validated in xenograft mouse model. RESULTS: In both cohorts, F. nucleatum-positive EGJ or gastric adenocarcinoma patients had notably shorter OS. F. nucleatum positivity decreased in more acidic tumour environments. Cancer cell lines with F. nucleatum showed enhanced proliferation and NF-κB activation. The xenograft model indicated increased tumour growth and NF-κB activation in F. nucleatum-treated cells. Interestingly, co-occurrence of F. nucleatum and Helicobacter pylori, a known risk factor, was rare. CONCLUSIONS: F. nucleatum can induce the NF-κB pathway in EGJ and gastric adenocarcinomas, leading to tumour progression and poor prognosis.

Laparoscopic versus open abdominal lymph node dissection for esophageal squamous cell carcinoma: a propensity score matching analysis.

PURPOSE: To compare the short- and long-term outcomes of laparoscopic and open abdominal lymph node dissection using propensity score matching (PSM) analysis. METHODS: The subjects of this retrospective analysis were 459 patients who underwent curative resection for esophageal squamous cell carcinoma (ESCC) between May, 2005 and December, 2019, at our hospital. Patients were divided into two groups: the Laparoscopic (Lap group) and the Open (Open group). Post-PSM, 139 patients from each group were selected for the analysis to compare the short- and long-term outcomes between the groups. RESULTS: The Lap group experienced fewer Clavien-Dindo (CD) Grade ≥ 2 complications (28.1% vs. 40.3%, P = 0.04) and lower rates of abdominal surgical site infections (SSI) (2.9% vs. 7.9%, P = 0.02) than the Open group. The number of lymph nodes harvested was similar in the Lap and Open groups (14.8 ± 7.5 vs. 15.7 ± 8.6, P = 0.34). There was no significant difference in 3-year overall survival rates (81.2% vs. 69.5%, P = 0.12) or relapse-free survival rates (61.1% vs. 58.2%, P = 0.54) between the groups. CONCLUSIONS: Laparoscopic abdominal lymph node dissection for ESCC can be performed safely and appears to be beneficial.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Distribution of Residual Disease and Recurrence Patterns in Pathological Responders After Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

OBJECTIVE: This study aimed to elucidate the residual disease distribution and recurrence patterns in patients with ESCC responding to NAC. SUMMARY BACKGROUND DATA: To appropriately plan a prospective trial for the organ preservation approach which includes additional chemoradiotherapy in patients who responded to NAC, the distribution of residual disease needs to be elucidated. Given that the residual tumor is located in the regional field, chemoradiotherapy can be safely added to eliminate the residual disease. METHODS: Overall, 483 patients with resectable ESCC who received NAC followed by transthoracic esophagectomy at 2 high-volume centers were reviewed. The recurrence-free survival, overall survival (OS), and residual and recurrent tumor patterns were compared among the pathological responses. RESULTS: Compared with nonpathological responders, pathological responders exhibited significantly longer recurrence-free survival [hazard ratio of Grade 1b/2/3 compared with Grade 0; 0.25 ( P < 0.001)/0.17 ( P < 0.001)/0.16 ( P = 0.003)] and OS [hazard ratio of Grade 1b/2/3 compared with Grade 0; 0.26 ( P < 0.001)/0.12 ( P < 0.001)/0.11 ( P = 0.003)]. In terms of the distribution of recurrence, the percentages of solitary recurrence in the regional field out of all recurrence was significantly higher in patients with Grade 1b (60%)/2 (67%)/3 (67%) whereas less than 25% in Grade 0 or 1a. CONCLUSIONS: It was found that postoperative recurrence in responders occurred in the regional field mostly as a solitary lesion without the distant failure, indicating that the residual tumor cells can be eliminated by additional chemoradiotherapy.

Pan-immune-inflammation Value and Prognosis in Patients With Esophageal Cancer.

Mini-abstract: The pan-immune-inflammation value was associated with clinical outcomes and tumor-infiltrating lymphocytes in 866 esophageal cancers. Systemic immune competence may influence patient prognosis through local immune response. Objective: To examine the relationship between the pan-immune-inflammation value (PIV), tumor immunity, and clinical outcomes in 866 patients with esophageal cancer. Background: The PIV, calculated from all immune-inflammatory cells in the peripheral blood count, is a recently proposed marker for clinical outcomes in some types of cancers. Nonetheless, the prognostic significance of PIV in esophageal cancer remains unclear. Methods: In the derivation cohort (n = 433), we set the optimal cutoff value using a time-dependent receiver operating characteristic (ROC) curve. In the validation cohort (n = 433), the relationships between the PIV, tumor-infiltrating lymphocytes (TILs), CD8 expression by immunohistochemical staining, and patient prognosis were examined. Results: The area under the ROC curve for the PIV at 5 years was 0.631 in the derivation cohort. The validation cohort, divided into PIV-low cases (n = 223) and PIV-high cases (n = 210), showed significantly worse overall survival (log-rank P = 0.0065; hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.12-1.98; P < 0.001; multivariate HR: 1.41; 95% CI: 1.05-1.90; P = 0.023). The prognostic effect of the PIV was not significantly modified by any clinical characteristics (P for interaction > 0.05). The PIV-high cases were significantly associated with a low TIL status (P < 0.001) and low CD8-positive cell counts (P = 0.011). Conclusions: The PIV was associated with clinical outcomes in esophageal cancer, supporting its role as a prognostic biomarker. Considering the relationship between the PIV and TILs, systemic immune competence may influence patient prognosis through a local immune response.

Immune-related adverse events and prognosis in patients with upper gastrointestinal cancer treated with nivolumab.

Background: Immune checkpoint inhibitors (ICIs) are increasingly being used for the treatment of upper gastrointestinal cancers [esophageal cancer and gastric cancer (GC)]. They cause imbalances in immunological tolerance, resulting in immune-related adverse events (irAEs). Although irAEs have been reported to be associated with the efficacy of ICIs in some cancers, the relationship between irAEs and prognosis of upper gastrointestinal cancers remains unknown. This study aimed to investigate the prognostic impact of irAEs in patients with advanced or recurrent upper gastrointestinal cancer treated with nivolumab. Methods: We retrospectively divided the patients (n=96) who received nivolumab into two groups: the irAEs group (n=41) and non-irAEs group (n=55), according to the Common Terminology Criteria for Adverse Events ver. 5.0. Results: irAEs were significantly associated with good performance status and high serum albumin levels (all P<0.05). The irAEs group had a significantly longer overall survival (OS) than the non-irAEs group [log-rank P=0.003; univariate hazard ratio (HR) =0.36, 95% confidence interval (CI) =0.21-0.65, P<0.01; multivariate HR =0.47, 95% CI =0.26-0.88, P=0.018]. Importantly, in both esophageal cancer and GC, the irAEs group experienced favorable clinical outcomes compared with the non-irAEs group. In the multivariate analysis, male sex (P<0.01), presence of irAEs (P=0.018), and good pretreatment performance status (P<0.01) were independent prognostic factors. Conclusions: Among patients with upper gastrointestinal cancer treated with nivolumab, the prognosis of patients who developed irAEs was better than that of patients who did not develop irAEs. Long-term continuation of nivolumab by early detection of irAEs and an appropriate response to irAEs are important.

Treatment strategies and outcomes for elderly patients with locally advanced squamous cell carcinoma of the esophagus.

PURPOSE: A multidisciplinary treatment strategy for locally advanced esophageal squamous cell carcinoma (ESCC) is required to achieve prolonged survival. We aimed to clarify the differences in treatment strategies for locally advanced ESCC and the outcomes of elderly (aged ≥ 75 years) vs. younger patients (aged < 75 years). METHODS: We compared the treatment strategy selection and the outcomes of 40 elderly and 160 younger patients with cStage II/III ESCC diagnosed between January, 2014 and December, 2016. RESULTS: Nineteen (47.5%) of the elderly patients and 144 (90.0%) of the younger patients underwent esophagectomy and 9 (22.5%) of the elderly patients and 131 (81.9%) of the younger patients received neoadjuvant chemotherapy. Ivor-Lewis or transhiatal esophagectomy was performed more frequently in the elderly group than in the younger group (P = 0.0096). The survival rate after esophagectomy was higher in the younger group than in the elderly group. The overall survival rate of the elderly patients who underwent esophagectomy was significantly higher than that in those who did not. CONCLUSIONS: Esophagectomy is a practical choice for elderly patients with locally advanced ESCC, although reduced treatment intensity may impact long-term survival.