Digestive and breast cancer patients managed during the first wave of COVID-19 pandemic: Short and middle term outcomes.

BACKGROUND: The first wave of coronavirus disease 2019 (COVID-19) pandemic in Spain lasted from middle March to the end of June 2020. Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods. In our centre, we managed patients previously and newly diagnosed with cancer. We established a strategy based on limiting perioperative social contacts, preoperative screening (symptoms and reverse transcription-polymerase chain reaction) and creating separated in-hospital COVID-19-free pathways for non-infected patients. We also adopted some practice modifications (surgery in different facilities, changes in staff and guidelines, using continuously changing personal protective equipment…), that supposed new inconveniences. AIM: To analyse cancer patients with a decision for surgery managed during the first wave, focalizing on outcomes and pandemic-related modifications. METHODS: We prospectively included adults with a confirmed diagnosis of colorectal, oesophago-gastric, liver-pancreatic or breast cancer with a decision for surgery, regardless of whether they ultimately underwent surgery. We analysed short-term outcomes [30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection] and outcomes after 3 years (adjuvant therapies, oncological events, death, SARS-CoV-2 infection and vaccination). We also investigated modifications to usual practice. RESULTS: From 96 included patients, seven didn't receive treatment that period and four never (3 due to COVID-19). Operated patients: 28 colon and 21 rectal cancers; laparoscopy 53.6%/90.0%, mortality 3.57%/0%, major complications 7.04%/25.00%, anastomotic leaks 0%/5.00%, 3-years disease-free survival (DFS) 82.14%/52.4% and overall survival (OS) 78.57%/76.2%. Six liver metastases and six pancreatic cancers: no mortality, one major complication, three grade A/B liver failures, one bile leak; 3-year DFS 0%/33.3% and OS 50.0%/33.3% (liver metastases/pancreatic carcinoma). 5 gastric and 2 oesophageal tumours: mortality 0%/50%, major complications 0%/100%, anastomotic leaks 0%/100%, 3-year DFS and OS 66.67% (gastric carcinoma) and 0% (oesophagus). Twenty breast cancer without deaths/major complications; 3-year OS 100% and DFS 85%. Nobody contracted SARS-CoV-2 postoperatively. COVID-19 pandemic-related changes: 78.2% treated in alternative buildings, 43.8% waited more than 4 weeks, two additional colostomies and fewer laparoscopies. CONCLUSION: Some patients lost curative-intent surgery due to COVID-19 pandemic. Despite practice modifications and 43.8% delays higher than 4 weeks, surgery was resumed with minimal changes without impacting outcomes. Clean pathways are essential to continue surgery safely.

Management for recurrent laryngeal nerve paralysis following oesophagectomy for oesophageal cancer: thoracic surgeon perspective.

Background: Recurrent laryngeal nerve (RLN) paralysis following oesophagectomy may increase postoperative morbidity and mortality. However, clinical studies on this complication are uncommon. The aim of this study was to report the clinical course of patients with RLN paralysis following oesophageal cancer surgery. Methods: We retrospectively examined patients who underwent oesophagectomy for oesophageal carcinoma at Asan Medical Center between January 2013 and November 2018. We enrolled 189 patients with RLN paralysis confirmed using laryngoscopy in this study. Results: Of the 189 patients, 22 patients had bilateral RLN paralysis, and 167 patients had unilateral RLN paralysis. Every patient received oral feeding rehabilitation, and 145 (76.7%) patients received hyaluronic acid injection laryngoplasty. During the postoperative period, 21 (11.1%) patients experienced aspiration pneumonia and recovered. One patient died of severe pulmonary complication. Twenty-four (12.7%) patients underwent feeding jejunotomy, while 11 (5.9%) patients underwent tracheostomy. In total, 173 (91.5%) patients were discharged with oral nutrition, and the median time to begin oral diet was 9 days. Statistical analysis using logistic regression revealed that only the advanced T stage affected nerve recovery. More than 50% of the patients showed nerve recovery within 6 months, and 165 (87.9%) patients fully or partially recovered during the observation period. Conclusions: RLN paralysis following oesophagectomy in oesophageal carcinoma is a predictable complication. In patients with RLN paralysis, early detection and intervention through multidisciplinary cooperation are required, and the incidence of postoperative complications can be reduced by implementing the appropriate management.

Gastroesophageal signet ring cell carcinoma morbidity and mortality: A retrospective review.

BACKGROUND: Upper gastrointestinal (GI) signet ring cell carcinomas (SRCC) confer a poor prognosis. The benefit of operative intervention for this patient group is controversial in terms of overall survival. AIM: To investigate factors relating to survival in patients with upper GI SRCC. METHODS: A retrospective, tertiary, single-centre review of patients who were diagnosed with oesophageal, gastroesophageal junction and gastric SRCC was performed. The primary outcome was to compare mortality of patients who underwent operative management with those who had nonoperative management. Secondary outcomes included assessing the relationship between demographic and histopathological factors, and survival. RESULTS: One hundred and thirty-one patients were included. The one-year survival for the operative group was 81% and for the nonoperative group was 19.1%. The five-year survival in the operative group was 28.6% vs 1.5% in the nonoperative group. The difference in overall survival between groups was statistically significant (HR 0.19, 95%CI (0.13-0.30), P < 0.001). There was no difference in survival when adjusting for age, smoking status or gender. On multivariate analysis, patients who underwent surgical management, those with a lower stage of disease, and those with a lower Charlson Comorbidity Index (CCI) had significantly improved survival. CONCLUSION: Well-selected patients with upper GI SRCC appear to have reasonable medium-term survival following surgery. Offering surgery to a carefully selected patient group may improve the outcome for this disease.

GABRP inhibits the progression of oesophageal cancer by regulating CFTR: Integrating bioinformatics analysis and experimental validation.

Oesophageal cancer (EC) is a malignancy which accounts for a substantial number of cancer-related deaths worldwide. The molecular mechanisms underlying the pathogenesis of EC have not been fully elucidated. GSE17351 and GSE20347 data sets from the Gene Expression Omnibus (GEO) database were employed to screen differentially expressed genes (DEGs). Reverse transcription quantitative PCR (RT-qPCR) was used to examine hub gene expression. ECA-109 and TE-12 cells were transfected using the pcDNA3.1 expression vector encoding GABRP. The cell counting kit-8 (CCK-8), cell scratch and Transwell assays were performed to assess the effect of GABRP on EC cell proliferation, migration and invasion. Epithelial-mesenchymal transition (EMT)-associated protein levels were measured by Western blotting. Subsequently, CFTR was knocked down to verify whether GABRP affected biological events in EC cells by targeting CFTR. Seven hub genes were identified, including GABRP, FLG, ENAH, KLF4, CD24, ABLIM3 and ABLIM1, which all could be used as diagnostic biomarkers for EC. The RT-qPCR results indicated that the expression levels of GABRP, FLG, KLF4, CD24, ABLIM3 and ABLIM1 were downregulated, whereas the expression level of ENAH was upregulated. In vitro functional assays demonstrated that GABRP overexpression suppressed the proliferation, migration, invasion and EMT of EC cells. Mechanistically, GABRP promoted the expression of CFTR, and CFTR knockdown significantly counteracted the influence of GABRP overexpression on biological events in EC cells. Overexpression of GABRP inhibited EC progression by increasing CFTR expression, which might be a new target for EC treatment.

Long-term impact of aerodigestive symptoms on adults with oesophageal cancer: A qualitative study.

PURPOSE: The impact of long-term aerodigestive symptoms following oesophageal cancer surgery is still not well understood. This study aimed to qualitatively understand the long-term impact of aerodigestive symptoms on quality of life in adults post-oesophagectomy. METHOD: Participants who received curative transhiatal/transthoracic surgery for oesophageal cancer in Ireland's National Oesophageal Cancer Centre were invited to attend semi-structured interviews. Surgery had to be completed at least 12 months prior. Reflexive thematic analysis was conducted. RESULT: Forty participants were interviewed individually face-to-face. Four key themes were identified: (a) isolation, reflecting the reported solitude experienced by oesophageal cancer survivors when attempting to manage their ongoing aerodigestive symptoms; (b) fear, including fear of choking and fear that dysphagia symptoms may indicate recurrence of oesophageal cancer; (c) altered work capacity, caused by ongoing aerodigestive symptoms; and (d) avoidance of social situations involving food, due to the pain, discomfort, and embarrassment caused by these symptoms. CONCLUSION: Oesophageal cancer treatment can be lifesaving, however, such medical interventions can result in distressing physiological aerodigestive symptoms throughout survivorship, which can significantly impact quality of life. Our findings indicate a need for greater community support to manage aerodigestive symptoms and reduce the impact these have on quality of life.

Incidence of acute kidney injury and its associated risk factors in patients undergoing elective oesophagectomy surgeries at a tertiary care cancer institute - A pilot prospective observational study.

Background and Aims: Acute kidney injury (AKI) is a significant postoperative complication. Multiple perioperative factors are implicated in the causation of AKI in the postoperative period in patients with oesophageal cancer. The study aimed to find out the incidence, causes and effects of AKI following oesophagectomy surgery. Methods: A prospective observational study was conducted in consecutive adult patients undergoing elective oesophagectomy at a tertiary cancer care hospital. Patients with preoperative chronic renal insufficiency (serum creatinine >1.5 mg/dl), AKI in the past and a history of renal replacement therapy were excluded. Serum creatinine values were measured on postoperative days 1, 3, 5, the day of discharge or day 15 and on the day of first follow-up or day 28, following oesophagectomy surgery. The incidence of AKI was measured using the 'Kidney Disease Improving Global Outcome' (KDIGO) criteria. Results: The incidence of AKI was 14.7% [95% confidence interval (CI) 9.9%, 20.7%] (i.e., 27/183) in patients who underwent elective oesophagectomy. AKI was associated with prolonged hospital stay [median- 13 days (interquartile range {IQR} 11-21.5) versus 9 days (IQR 8-12), P < 0.001] and increased in-hospital mortality (14.8% versus 1.3%, P 0.004, odds ratio = 13.2, 95% CI 2.3, 77.3). After multivariate analysis, age, anastomotic leak and use of vasopressors in the postoperative period were independent predictors of AKI. Conclusion: The incidence of AKI was 14.7% after elective oesophagectomy. AKI was associated with prolonged hospital stay and in-hospital mortality. Higher age, anastomotic leak and use of vasopressors in the postoperative period were independent predictors of AKI.

Practice pattern and risk of not receiving planned surgery after neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma.

OBJECTIVES: Unlike the initial plan, some patients with oesophageal squamous cell carcinoma cannot or do not receive surgery after neoadjuvant chemoradiotherapy (nCRT). This study aimed to report the epidemiology of patients not receiving surgery after nCRT and to evaluate the potential risk of refusing surgery. METHODS: We analysed patients with clinical stage T3-T4aN0M0 or T1-T4aN1-N3M0 oesophageal squamous cell carcinoma who underwent nCRT as an initial treatment intent between January 2005 and March 2020. Patients not receiving surgery were categorized using predefined criteria. To evaluate the risk of refusing surgery, a propensity-matched comparison with those who received surgery was performed. Recurrence-free (RFS) and overall survival (OS) was compared between groups, according to clinical response to nCRT. RESULTS: Among the study population (n = 715), 105 patients (14.7%) eventually failed to reach surgery. There were three major patterns of not receiving surgery: disease progression before surgery (n = 25), functional deterioration at reassessment (n = 47), and patient's refusal without contraindications (n = 33). After propensity-score matching, the RFS curves of the surgery group and the refusal group were significantly different (P < 0.001), while OS curves were not significantly different (P = 0.069). In patients who achieved clinical complete response on re-evaluation, no significant difference in the RFS curves (P = 0.382) and in the OS curves (P = 0.290) was observed between the surgery group and the refusal group. However, among patients who showed partial response or stable disease on re-evaluation, the RFS and OS curves of the refusal group were overall significantly inferior compared to those of the surgery group (both P < 0.001). The 5-year RFS rates were 10.3% for the refusal group and 48.2% for the surgery group, and the 5-year OS rates were 8.2% for the refusal group and 46.1% for the surgery group. CONCLUSIONS: Patient's refusal remains one of the major obstacles in completing the trimodality therapy for oesophageal squamous cell carcinoma. Refusing surgery when offered may jeopardize oncological outcome, particularly in those with residual disease on re-evaluation after nCRT. These results provide significant implications for consulting patients who are reluctant to oesophagectomy after nCRT.

Indocyanine green fluorescence imaging technology for the treatment of chylothorax after oesophageal cancer: A case report.

Chylothorax is a serious postoperative complication of oesophageal cancer, and to date, there is no standardized and effective intraoperative diagnostic tool that can be used to identify the thoracic duct and determine the location of lymphatic fistulas. A 50-year-old patient with oesophageal squamous cell carcinoma developed chylothorax after thoracolaparoscopy combined with radical resection of oesophageal cancer. Twelve hours after surgery, 1200 mL of clear fluid was drained from the thoracic drainage tube, and a chyle test was sent. A thoracothoracic duct ligation procedure was performed on the first day after surgery. Although fluid accumulating in the posterior mediastinum was observed, the location of the lymphatic fistula could not be determined. During the surgery, indocyanine green (ICG) was injected into the bilateral inguinal lymph nodes, and a fluorescent lens was used to determine the location of the lymphatic fistula so the surgeon could ligate the thoracic duct. ICG fluorescence imaging technology can help surgeons effectively manage chylothorax after oesophageal cancer surgery. To our knowledge, this is the first report to describe the use of ICG fluorescence imaging technology to treat postoperative chylothorax in patients with oesophageal cancer in China.

Chronic atrophic gastritis and risk of incident upper gastrointestinal cancers: a systematic review and meta-analysis.

BACKGROUND: Previous literature has explored the relationship between chronic atrophic gastritis (CAG) and isolated cancers within the upper gastrointestinal cancers; However, an integrative synthesis across the totality of upper gastrointestinal cancers was conspicuously absent. The research objective was to assess the relationship between CAG and the risk of incident upper gastrointestinal cancers, specifically including gastric cancer, oesophageal cancer, and oesophagogastric junction cancer. METHODS: Rigorous systematic searches were conducted across three major databases, namely PubMed, Embase and Web of Science, encompassing the timeline from database inception until August 10, 2023. We extracted the necessary odds ratio (OR) and their corresponding 95% confidence interval (CI) for subsequent meta-analysis. Statistical analyses were conducted using Stata 17.0 software. RESULTS: This meta-analysis included a total of 23 articles encompassing 5858 patients diagnosed with upper gastrointestinal cancers. CAG resulted in a statistically significant 4.12-fold elevated risk of incident gastric cancer (OR = 4.12, 95% CI 3.20-5.30). Likewise, CAG was linked to a 2.08-fold increased risk of incident oesophageal cancer (OR = 2.08, 95%CI 1.60-2.72). Intriguingly, a specific correlation was found between CAG and the risk of incident oesophageal squamous cell carcinoma (OR = 2.29, 95%CI 1.77-2.95), while no significant association was detected for oesophageal adenocarcinoma (OR = 0.62, 95%CI 0.17-2.26). Moreover, CAG was correlated with a 2.77-fold heightened risk of oesophagogastric junction cancer (OR = 2.77, 95%CI 2.21-3.46). Notably, for the same type of upper gastrointestinal cancer, it was observed that diagnosing CAG through histological methods was linked to a 33-77% higher risk of developing cancer compared to diagnosing CAG through serological methods. CONCLUSION: This meta-analysis indicated a two- to fourfold increased risk of gastric cancer, oesophageal cancer, and oesophagogastric junction cancer in patients with CAG. Importantly, for the same upper gastrointestinal cancer, the risk of incident cancer was higher when CAG was diagnosed histologically compared to serological diagnosis. Further rigorous study designs are required to explore the impact of CAG diagnosed through both diagnostic methods on the risk of upper gastrointestinal cancers.

Current trends in the management of Gastro-oEsophageal cancers: Updates to the ESSO core curriculum (ESSO-ETC-UGI-WG initiative).

Gastro-oEsophageal Cancers (GECs) are severe diseases whose management is rapidly evolving. The European Society of Surgical Oncology (ESSO) is committed to the generation and spread of knowledge, and promotes the multidisciplinary management of cancer patients through its core curriculum. The present work discusses the approach to GECs, including the management of oligometastatic oesophagogastric cancers (OMEC), the diagnosis and management of peritoneal metastases from gastric cancer (GC), the management of Siewert Type II tumors, the importance of mesogastric excision, the role of robotic surgery, textbook outcomes, organ preserving options, the use of molecular markers and immune check-point inhibitors in the management of patients with GECs, as well as the improvement of current clinical practice guidelines for the management of patients with GECs. The aim of the present review is to provide a concise overview of the state-of-the-art on the management of patients with GECs and, at the same time, to share the latest advancements in the field and to foster the debate between surgical oncologists treating GECs worldwide. We are sure that our work will, at the same time, give an update to the advanced surgical oncologists and help the training surgical oncologists to settle down the foundations for their future practice.

CDC73 serves as a tumour-promoting factor in oesophageal cancer.

The role of human cell division cycle 73 (CDC73) in human cancers has sparked controversy; however, its significance in oesophageal cancer remains elusive. This study aimed to elucidate CDC73 expression and its biological implications in human oesophageal cancer. Our findings unveiled a notable upregulation of CDC73 in both oesophageal cancer cell lines and tissues. Importantly, elevated CDC73 levels in patients with oesophageal cancer correlated with an unfavourable prognosis. Functional investigations revealed that CDC73 knockdown effectively curtailed the proliferation and growth of oesophageal cancer cells both in vitro and in vivo. Mechanistically, RRP15 emerged as a potential downstream target of CDC73 through a screening process involving identification of the top co-expressed genes, subsequent knockdown experiments, and observation of significant inhibition of cell proliferation, with RRP15 showing the most pronounced effect. This finding was further supported by the positive correlation observed between CDC73 and RRP15 in ESCA samples analysed using the ENCORI Pan-Cancer Analysis Platform. Notably, depletion of RRP15 in CDC73-overexpressing cells led to a shift from augmented to diminished tumour growth. Collectively, our findings underscore the pivotal role of CDC73 in oesophageal cancer through the modulation of RRP15 expression, suggesting CDC73 as a potential therapeutic target for treating oesophageal cancer.

Comprehensive Rehabilitation Strategies in Esophageal Cancer: A Case Report of Enhancing Recovery and Quality of Life.

Esophageal cancer is a significant global health burden; it is the seventh most commonly diagnosed cancer and the sixth leading cause of cancer-related deaths globally. It accounts for 3.2% of newly diagnosed malignancies; adenocarcinoma and squamous cell carcinoma are the most prevalent histological subtypes. Clinical presentation often includes dysphagia, odynophagia, weight loss, and persistent heartburn. Diagnosis is confirmed through endoscopy and imaging studies, with treatment typically involving chemotherapy, surgery, and/or radiation therapy. Physiotherapy plays a crucial role in managing pulmonary complications and improving overall cardiopulmonary function in these patients. We present the case of a 70-year-old woman with esophageal cancer, detailing her symptoms, diagnostic assessment, therapeutic interventions, and outcomes, highlighting the importance of a multidisciplinary approach in managing this challenging condition.

Nutritional responsiveness affects novel neutrophil parameters and reduces in-hospital mortality and costs in elective cancer oesophagectomy - a single centre, prospective, observational study.

INTRODUCTION: Malnutrition in surgical patients remains a common issue affecting the perioperative period. Oesophageal cancer is a disease associated with one of the highest malnutrition rates. Assessment of patient nutritional status remains a challenge due to limited validated tools. Novel parameters to identify malnourished patients and the effectiveness of preoperative nutritional intervention might improve treatment results in the perioperative period. MATERIAL AND METHODS: This was a prospective, observational, single-centre study of patients scheduled for elective oesophagectomy. The primary aim of this study was to establish the correlation between neutrophil reactivity intensity (NEUT-RI) and neutrophil granularity intensity (NEUT-GI) and patients' nutritional status. We divided patients into nutritional responders (R group) and nutritional non-responders (NR group) defined as regaining at least 25% of the maximum preoperative body weight loss during the preoperative period. RESULTS: The R group had significantly shorter intensive care unit (ICU) stays: 5.5 (4-8) vs. 13 (7-31) days ( P = 0.01). It resulted in a lower cost of ICU stays in the R group: 4775.2 (3938.9-7640.7) vs. 12255.8 (7787.6-49108.7) euro in the NR group ( P = 0.01). Between the R group and the NR group, we observed statistically significant differences in both preoperative NEUT-RI (48.6 vs. 53.4, P = 0.03) and NEUT-GI (154.6 vs. 159.3, P = 0.02). Apart from the T grade, the only preoperative factor associated with reduced mortality was the nutritional responsiveness: 11.1% vs. 71.4% ( P = 0.008). CONCLUSIONS: Preoperative nutritional responsiveness affects neutrophil intensity indexes and reduces in-hospital mortality and costs associated with hospital stay. Further research is required to determine the correlation between novel neutrophil parameters and patients' nutritional status.

Multi-stage surgery to treat oesophageal fistula that developed after chemoradiotherapy in two patients with oesophageal cancer: A case report.

INTRODUCTION AND IMPORTANCE: Oesophageal fistula is a severe complication that may occasionally develop after chemoradiotherapy (CRT) for oesophageal cancer and is difficult to treat. CASE PRESENTATION: A 51-year-old man who had undergone CRT for oesophageal cancer presented with haematemesis and was diagnosed with a descending aortic aneurysm and an oesophageal fistula. Thoracic endovascular aneurysm repair was performed to achieve haemostasis. After 3 days, the patient underwent subtotal oesophagectomy and cervical oesophagostomy with delivery of a pedicled omental flap to the exposed aortic stent. Six months later, ileocecal reconstruction was performed. The second patient was a 49-year-old woman who had undergone CRT 1 year previously. She complained of leg weakness and gait disorder. After a workup, she was diagnosed with perforation of the posterior wall of the cervical oesophagus with abscess formation and purulent spondylitis. After two spinal fusion surgeries, we performed tracheotomy and drained the cervical region to reduce local infection. After 7 days, she underwent pharyngolaryngoesophagectomy and reconstruction using a gastric conduit, to which a large section of the omental flap was attached. After the multi-stage surgery, oral intake became possible, and both patients were discharged. CLINICAL DISCUSSION: The optimal treatment strategy for post-CRT oesophageal fistula remains controversial. Radical surgery, including oesophagectomy, is the treatment of choice, although it is associated with high mortality rates. Multi-stage surgery may be useful for reducing surgical stress in moribund patients. CONCLUSION: We reported two cases involving radiation-induced oesophageal fistula successfully treated by multi-stage surgery without major complications.

Systematic Review of Hypofractionated Radiation Therapy for the Treatment of Oesophageal Squamous Cell Carcinoma and Oesophageal Adenocarcinoma.

BACKGROUND AND AIM: There has been limited progress made in improving the suboptimal outcomes delivered by conventionally fractionated radiotherapy (RT) for oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). A greater biological effect may be achieved using hypofractionated RT (HFRT), though the toxicity, tolerability and efficacy of this approach in OAC and OSCC is uncertain. METHODS: A systematic literature review was carried out in accordance with Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane, CINAHL, Scopus and Web of Science databases were searched for terms relating to HFRT (>2.4Gy per fraction) for OAC or OSCC. All relevant clinical studies published between January 2000 and April 2023 were included. Study quality was assessed using predefined criteria. RESULTS: Ninety-six studies were screened and 20 subsequently included, together incorporating 1208 patients. Fourteen studies focussed on neoadjuvant or definitive treatment. These were predominantly retrospective (n = 10, 71%) though two (n = 2, 14%) early phase trials were identified. Most focussed on OSCC (n = 7, 47%) or mixed OSCC/OAC (n = 6, 43%) populations. Four (28.6%) included a conventionally fractionated chemoradiotherapy (CRT) comparator, against which median overall (mOS) and progression free survival outcomes from HFRT did not differ. Reported mOS for HFRT ranged between 29-36 months at 2.5-3.125Gy per fraction (total dose 50-60Gy) for OAC and OSCC combined. Toxicity and tolerability with HFRT was comparable with conventionally fractionated CRT up to, but not exceeding, 5Gy. Three (50%) of the six palliative-intent studies were early phase trials and most (n = 4, 67%) focussed on OAC and OSCC. Response rates with HFRT in the palliative setting were 63.6-88.0%. CONCLUSION: These data provide evidence in OAC/OSCC for promising efficacy and an acceptable toxicity profile for moderately HFRT, alone or with concurrent chemotherapy. These data should prompt prospective, randomised comparisons of HFRT and conventionally fractionated CRT and single-modality RT schedules. REGISTRATION DETAILS: PROSPERO; CRD42023457791.

Detrimental impact of late-onset pneumonia on long-term prognosis in oesophageal cancer survivors.

BACKGROUD: Oesophageal cancer patients are prone to early- and late-onset pneumonia after oesophagectomy. We aimed to investigate the incidence rate and impact on the long-term prognosis of late-onset pneumonia in oesophageal cancer survivors who survived for at least one year after oesophagectomy without cancer recurrence. METHODS: We retrospectively reviewed 233 patients with thoracic oesophageal cancer who underwent oesophagectomy with gastric conduit reconstruction between September 2009 and June 2019 at a tertiary referral hospital in Japan. Pneumonia that occurred ≥1 year after oesophagectomy was defined as late-onset pneumonia. RESULTS: Among the 185 oesophageal cancer survivors, 31 (17%) developed late-onset pneumonia. The cumulative incidence rates of late-onset pneumonia 24, 36, and 60 months after oesophagectomy were 6.4%, 10%, and 21%, respectively, whereas pneumonia recurred at 21%, 31%, and 52% within 6, 12, and 24 months, respectively, after the first pneumonia. Chronic obstructive pulmonary disease, postoperative anastomotic leakage, and loss of skeletal muscle mass were independently associated with late-onset pneumonia, and a combination of these factors further increased the risk. Late-onset pneumonia with hospitalisation had the greatest negative impact on the long-term prognosis as non-cancer deaths (HR, 21; p < 0.001), followed by recurrent late-onset pneumonia (HR, 18; p < 0.001). CONCLUSIONS: Late-onset pneumonia in oesophageal cancer survivors is significantly associated with an increased risk of recurrent infections and non-cancer deaths. Chronic obstructive pulmonary disease and postoperative muscle loss are risk factors for late-onset pneumonia, and more intensive pharmacological and nutritional interventions should be considered to improve long-term prognosis after oesophagectomy.

Exploring Potential Biomarkers in Oesophageal Cancer: A Comprehensive Analysis.

Oesophageal cancer (OC) is the sixth leading cause of cancer-related death worldwide. OC is highly aggressive, primarily due to its late stage of diagnosis and poor prognosis for patients' survival. Therefore, the establishment of new biomarkers that will be measured with non-invasive techniques at low cost is a critical issue in improving the diagnosis of OC. In this review, we summarize several original studies concerning the potential significance of selected chemokines and their receptors, including inflammatory proteins such as interleukin-6 (IL-6) and C-reactive protein (CRP), hematopoietic growth factors (HGFs), claudins (CLDNs), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), adamalysines (ADAMs), as well as DNA- and RNA-based biomarkers, in OC. The presented results indicate the significant correlation between the CXCL12, CXCR4, CXCL8/CXCR2, M-CSF, MMP-2, MMP-9 ADAM17, ADAMTS-6, and CLDN7 levels and tumor stage, as well as the clinicopathological parameters of OC, such as the presence of lymph node and/or distant metastases. CXCL12, CXCL8/CXCR2, IL-6, TIMP-2, ADAM9, and ADAMTS-6 were prognostic factors for the overall survival of OC patients. Furthermore, IL-6, CXCR4, CXCL8, and MMP-9 indicate higher diagnostic utility based on the area under the ROC curve (AUC) than well-established OC tumor markers, whereas CLDN18.2 can be used in novel targeted therapies for OC patients.

Prognostic impact of muscle mass loss in elderly patients with oesophageal cancer receiving neoadjuvant chemoradiation therapy.

BACKGROUND: We aimed to identify the impact of muscle mass on locally advanced oesophageal cancer (LAEC) in elderly patients receiving neoadjuvant chemoradiation therapy (NACRT). METHODS: We reviewed the medical records of 345 patients diagnosed with LAEC who underwent NACRT and surgery. Physical variables, including height, weight, skeletal muscle mass, and laboratory values, were obtained before and after NACRT. Body mass index (BMI, kg/m2), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were calculated as height/(weight)2, ANC/ALC, platelet count/ALC, and (10 × albumin + 0.05 × ALC), respectively. The cutoff for low muscle mass was 43.0 cm2/m2 for BMI below 25 kg/m2 and 53.0 cm2/m2 for BMI 25 kg/m2 or higher. The skeletal muscle index (SMI) was defined as skeletal muscle area/(height)2 (cm2/m2). The ΔSMI (%/50 days) was defined as (SMI after NACRT - SMI before NACRT)/interval (days) × 50 (days) to compare changes over the same period. The excessive muscle loss (EML) group was defined as patients with ΔSMI ≤-10% following NACRT. An elderly patient was defined as aged ≥65 years. The primary outcome measure was overall survival (OS). RESULTS: During a median follow-up of 32.8 months (range, 2.0-176.2), 192 patients died, with a median OS of 50.2 months. Elderly patients did not show inferior OS (young vs. elderly, 57.7% vs. 54.0% at 3 years, P = 0.247). 71.0% and 87.2% of all patients had low muscle mass before and after NACRT, respectively, which was not associated with OS (P = 0.270 and P = 0.509, respectively). Inflammatory (NLR and PLR) and nutritional index (PNI) values or their changes did not correlate with OS. However, the EML group had worse OS (41.6% vs. 63.2% at 3 years, P < 0.0001). In the multivariate analysis, EML was also a significant prognostic factor for OS. In the subgroup analysis by age, EML was a strong prognostic factor for OS in the elderly group. The 3-year OS was 36.8% in the EML group and 64.9% in the non-EML group (P < 0.0001) in elderly patients, and 47.4% and 62.1% (P = 0.063) in the young patients. In multivariate analysis of each subgroup, EML remained prognostic only in the elderly group (P = 0.008). CONCLUSIONS: EML may be strongly associated with a deteriorated OS in elderly patients undergoing NACRT, followed by surgery for LAEC. The strategies for decreasing muscle loss in these patients should be investigated.