Minimally invasive Ivor Lewis esophagectomy in the elderly patient: a multicenter retrospective matched-cohort study.

Introduction: Several studies reported the advantages of minimally invasive esophagectomy over the conventional open approach, particularly in terms of postoperative morbidity and mortality. The literature regarding the elderly population is however scarce and it is still not clear whether elderly patients may benefit from a minimally invasive approach as the general population. We sought to evaluate whether thoracoscopic/ laparoscopic (MIE) or fully robotic (RAMIE) Ivor-Lewis esophagectomy significantly reduces postoperative morbidity in the elderly population. Methods: We analyzed data of patients who underwent open esophagectomy or MIE/RAMIE at Mainz University Hospital and at Padova University Hospital between 2016 and 2021. Elderly patients were defined as those ≥ 75 years old. Clinical characteristics and the postoperative outcomes were compared between elderly patients who underwent open esophagectomy or MIE/RAMIE. A 1-to-1 matched comparison was also performed. Patients < 75 years old were evaluated as a control group. Results: Among elderly patients MIE/RAMIE were associated with a lower overall morbidity (39.7% vs. 62.7%, p=0.005), less pulmonary complications (32.8 vs. 56.9%, p=0.003) and a shorter hospital stay (13 vs. 18 days, p=0.03). Comparable findings were obtained after matching. Similarly, among < 75 years-old patients, a reduced morbidity (31.2% vs. 43.5%, p=0.01) and less pulmonary complications (22% vs. 36%, p=0.001) were detected in the minimally invasive group. Discussion: Minimally invasive esophagectomy improves the postoperative course of elderly patients reducing the overall incidence of postoperative complications, particularly of pulmonary complications.

C-terminal agrin fragment as a biomarker of muscle wasting and weakness: a narrative review.

Ageing is accompanied by an inexorable loss of muscle mass and functionality and represents a major risk factor for numerous diseases such as cancer, diabetes and cardiovascular and pulmonary diseases. This progressive loss of muscle mass and function may also result in the insurgence of a clinical syndrome termed sarcopenia, exacerbated by inactivity and disease. Sarcopenia and muscle weakness yield the risk of falls and injuries, heavily impacting on health and social costs. Thus, screening, monitoring and prevention of conditions inducing muscle wasting and weakness are essential to improve life quality in the ageing modern society. To this aim, the reliability of easily accessible and non-invasive blood-derived biomarkers is being evaluated. C-terminal agrin fragment (CAF) has been widely investigated as a neuromuscular junction (NMJ)-related biomarker of muscle dysfunction. This narrative review summarizes and critically discusses, for the first time, the studies measuring CAF concentration in young and older, healthy and diseased individuals, cross-sectionally and in response to inactivity and physical exercise, providing possible explanations behind the discrepancies observed in the literature. To identify the studies investigating CAF in the above-mentioned conditions, all the publications found in PubMed, written in English and measuring this biomarker in blood from 2013 (when CAF was firstly measured in human serum) to 2022 were included in this review. CAF increases with age and in sarcopenic individuals when compared with age-matched, non-sarcopenic peers. In addition, CAF was found to be higher than controls in other muscle wasting conditions, such as diabetes, COPD, chronic heart failure and stroke, and in pancreatic and colorectal cancer cachectic patients. As agrin is also expressed in kidney glomeruli, chronic kidney disease and transplantation were shown to have a profound impact on CAF independently from muscle wasting. CAF concentration raises following inactivity and seems to be lowered or maintained by exercise training. Finally, CAF was reported to be cross-sectionally correlated to appendicular lean mass, handgrip and gait speed; whether longitudinal changes in CAF are associated with those in muscle mass or performance following physical exercise is still controversial. CAF seems a reliable marker to assess muscle wasting in ageing and disease, also correlating with measurements of appendicular lean mass and muscle function. Future research should aim at enlarging sample size and accurately reporting the medical history of each patient, to normalize for any condition, including chronic kidney disease, that may influence the circulating concentration of this biomarker.

Multimodal treatment of radiation-induced esophageal cancer: Results of a case-matched comparative study from a single center.

PURPOSE: Radiation-induced esophageal cancer (RIEC) is a rare but severe late consequence of radiotherapy. The literature regarding this topic is predominately limited in describing the risk of this disease. Tumor behavior, treatment strategies, and prognosis of this cancer remain poorly defined. PATIENTS AND METHODS: We collected data of patients who were referred to our unit between 2000 and 2020 for RIEC. After tumor board discussion, upfront surgery or neoadjuvant therapy and surgery were indicated as the main treatment. Preoperative characteristics, long-term and short-term postoperative outcomes of RIEC patients were compared with a 1:1 clustering-matched cohort of patients affected by primary esophageal cancer (PEC). RESULTS: At pre-matching, 54 RIEC and 936 PEC patients were enrolled. The median time between primary irradiation and diagnosis of RIEC was 13.5 years, and the median primary radiation dose was 60 Gy. Compared to the unmatched cohort of PECs, RIEC patients were more frequently female (p = 0.0007), had earlier detection of disease (p = 0.03) and presented more frequently with upper esophageal cancers (p < 0.0001). Neoadjuvant treatment was used less frequently in RIEC patients (p < 0.0001). After matching, the 51 RIEC and 50 PEC patients showed comparable results in terms of exposure to neoadjuvant treatment, surgical radicality and survival outcomes. RIEC patients had more severe postoperative complications (p = 0.04) and a higher proportion of pulmonary complications (p = 0.04). CONCLUSIONS: Curative treatments are feasible for RIEC. Neoadjuvant chemotherapy or chemoradiation can be used in this subgroup, treatment response and long-term outcomes are comparable to those of PEC. The risk of postoperative complications is probably related to the detrimental effect of primary irradiation on lung function.

Could the Pittsburgh Severity Score guide the treatment of esophageal perforation? Experience of a single referral center.

BACKGROUND: Esophageal perforation (EP) is characterized by high morbidity and mortality. The Pittsburgh Severity Score (PSS) is a scoring system based on clinical factors at the time of EP presentation, intended to guide treatment. The aim of the study is to verify PSS usefulness in stratifying EP severity and in guiding clinical decisions. METHODS: All patients referred to our unit for EP between January 2005 and January 2020 were enrolled. Patients were stratified according to their PSS into three groups (PSS ≤ 2, 3-5, and >5): the postoperative outcomes were compared. The predictive value of the PSS was evaluated by simple linear and logistic regression for the following outcomes: need for surgery, complications, in-hospital mortality, intensive care unit (ICU) and hospital stay, time to refeeding, and need for reintervention. RESULTS: Seventy-three patients were referred for EP (male/female, 46/27). Perforations were more frequently iatrogenic (41.1%) or spontaneous (38.3%). The median PSS was 4 (interquartile range, 2-6). Surgery was required in 60.3% of cases. Pittsburgh Severity Score was associated with ICU admission, hospital stay, need for surgery and reintervention, postperforation complications and mortality. After regression analysis, PSS was significantly predictive of postperforation complications (p < 0.01), in-hospital mortality (p = 0.01), ICU admission (p < 0.01), need for surgical treatment (p < 0.01), and need for reintervention (p = 0.02). CONCLUSION: Pittsburgh Severity Score is useful in stratifying patients in risk groups with different morbidity and mortality. It is also useful in guiding the therapeutic conduct, selecting patients for nonoperative management. Prospective studies are needed to confirm the role of the PSS in the treatment of esophageal perforation. LEVEL OF EVIDENCE: Management, Therapeutic/Care; level IV.

Pharyngo-Esophageal Perforation Following Anterior Cervical Spine Surgery: A Single Center Experience and a Systematic Review of the Literature.

STUDY DESIGN: Case series and systematic review of the Literature. OBJECTIVES: Pharyngo-esophageal perforation (PEP) is a rare, life-threatening complication of anterior cervical spine surgery (ACSS). Best management of these patients remains poorly defined. The aim of this study is to present our experience with this entity and to perform a systematic Literature review to better clarify the appropriate treatment of these patients. METHODS: Patients referred to our center for PEP following ACSS (January 2002-December 2018) were identified from our database. Moreover, an extensive review of the English Literature was conducted according to the 2009 PRISMA guidelines. RESULTS: Twelve patients were referred to our Institution for PEP following ACSS. Indications for ACSS were trauma (n = 10), vertebral metastases (n = 1) and disc herniation (n = 1). All patients underwent hardware placement at the time of ACSS. There were 6 early and 6 delayed PEP. Surgical treatment was performed in 11 patients with total or partial removal of spine fixation devices, autologous bone graft insertion or plate/cage replacement, anatomical suture of the fistula and suture line reinforcement with myoplasty. Complete resolution of PEP was observed in 6 patients. Five patients experienced PEP persistence, requiring further surgical management in 2 cases. At a median follow-up of 18.8 months, all patients exhibited permanent resolution of the perforation. CONCLUSIONS: PEP following ACSS is a rare but dreadful complication. Partial or total removal of the fixation devices, direct suture of the esophageal defect and coverage with tissue flaps seems to be an effective surgical approach in these patients.

Perturbed BMP signaling and denervation promote muscle wasting in cancer cachexia.

Most patients with advanced solid cancers exhibit features of cachexia, a debilitating syndrome characterized by progressive loss of skeletal muscle mass and strength. Because the underlying mechanisms of this multifactorial syndrome are incompletely defined, effective therapeutics have yet to be developed. Here, we show that diminished bone morphogenetic protein (BMP) signaling is observed early in the onset of skeletal muscle wasting associated with cancer cachexia in mouse models and in patients with cancer. Cancer-mediated factors including Activin A and IL-6 trigger the expression of the BMP inhibitor Noggin in muscle, which blocks the actions of BMPs on muscle fibers and motor nerves, subsequently causing disruption of the neuromuscular junction (NMJ), denervation, and muscle wasting. Increasing BMP signaling in the muscles of tumor-bearing mice by gene delivery or pharmacological means can prevent muscle wasting and preserve measures of NMJ function. The data identify perturbed BMP signaling and denervation of muscle fibers as important pathogenic mechanisms of muscle wasting associated with tumor growth. Collectively, these findings present interventions that promote BMP-mediated signaling as an attractive strategy to counteract the loss of functional musculature in patients with cancer.

The Prognostic Value of Low Muscle Mass in Pancreatic Cancer Patients: A Systematic Review and Meta-Analysis.

Low muscle mass is associated with reduced survival in patients with different cancer types. The interest in preoperative sarcopenia and pancreatic cancer has risen in the last decade as muscle mass loss seems to be associated with poorer survival, higher postoperative morbidity, and mortality. The aim of the present study was to review the literature to compare the impact of low muscle mass on the outcomes of patients undergoing surgery for pancreatic adenocarcinoma. An extensive literature review was conducted according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and 10 articles were analyzed in detail and included in the meta-analysis. Data were retrieved on 2811 patients undergoing surgery for pancreatic cancer. Meta-analysis identified that patients with low muscle mass demonstrated a significantly reduced OS when compared to patients without alterations of the muscle mass (ROM 0.86; 95% CI: 0.81-0.91, p < 0.001), resulting in a 14% loss for the former. Meta-analysis failed to identify an increase in the postoperative complications and length of stay of patients with low muscle mass. Our analysis confirms the role of low muscle mass in influencing oncologic outcomes in pancreatic cancer. Its role on surgical outcomes remains to be established.

Optimal Treatment of cT2N0 Esophageal Carcinoma: Is Upfront Surgery Really the Way?

BACKGROUND: Staging is inaccurate for cT2N0 esophageal cancer, and patients often are clinically mis-staged. This study aimed to evaluate the outcome after upfront surgery or neoadjuvant therapy, considering the impact of clinical "mis-staging." METHODS: This study reviewed patients with squamous cell carcinoma (SCC) or adenocarcinoma (ADK) of the esophagus who underwent upfront surgery (S group) or neoadjuvant treatment (chemoradiotherapy [CRT] group) for cT2N0 cancer. Overall survival (OS), disease-free survival (DFS), morbidity, and mortality were evaluated. Correctly staged (cTNM = pTNM), understaged (cTNM < pTNM), and overstaged (cTNM > pTNM) patients in the S group and the CRT group were analyzed. Risk factors for unexpected lymph-node involvement were identified in the S group and for cancer-related death in the whole study cohort. RESULTS: The study enrolled 229 patients with cT2N0 esophageal cancer. The 5-year OS rate was 34.2% in the S group versus 55.7% in the CRT group (p = 0.0088). The DFS also was significantly higher (p = 0.01). The morbidity and mortality rates were similar. In the S group, the cTNM was correctly staged for 21.4% and understaged for 63.4% of the patients, with 48.7% of the patients showing unexpected nodal involvement. A tumor length of 3 cm or more was an independent predictor of nodal metastases in SCC (p = 0.03), as was lymphovascular invasion (LVI) in ADK (p < 0.01). Cancer-related mortality was independently associated with lymph-node metastases (p = 0.03) and treatment by upfront surgery (p = 0.01). CONCLUSION: Given the high rate of understaged patients in this study (63.4%), the authors advocate for combining the induction therapy with surgery in cT2N0, achieving better survival with similar morbidity and mortality.

Foodborne botulism presenting as small bowel obstruction: a case report.

BACKGROUND: Small bowel obstruction is one of the leading reasons for accessing to the Emergency Department. Food poisoning from Clostridium botulinum has emerged as a very rare potential cause of small bowel obstruction. The relevance of this case report regards the subtle onset of pathognomonic neurological symptoms, which can delay diagnosis and subsequent life-saving treatment. CASE PRESENTATION: A 24-year-old man came to our Emergency Department complaining of abdominal pain, fever and sporadic self-limiting episodes of diplopia, starting 4 days earlier. Clinical presentation and radiological imaging suggested a case of small bowel obstruction. Non-operative management was adopted, which was followed by worsening of neurological signs. On specifically questioning the patient, we discovered that his parents had experienced similar, but milder symptoms. The patient also recalled eating home-made preserves some days earlier. A clinical diagnosis of foodborne botulism was established and antitoxin was promptly administered with rapid clinical resolution. CONCLUSIONS: Though very rare, botulism can mimic small bowel obstruction, and could be associated with a rapid clinical deterioration if misdiagnosed. An accurate family history, frequent clinical reassessments and involvement of different specialists can guide to identify this unexpected diagnosis.

Cervical Esophageal Cancer Treatment Strategies: A Cohort Study Appraising the Debated Role of Surgery.

BACKGROUND: Few studies have examined optimal treatment specifically for cervical esophageal carcinoma. This study evaluated the outcome of three common treatment strategies with a focus on the debated role of surgery. METHODS: All patients with cervical esophageal cancer treated at a single center were identified and their outcomes analyzed in terms of morbidity, mortality, and recurrence according to the treatment they received, i.e. surgery alone, definitive platinum-based chemoradiation (CRT), or CRT followed by surgery. RESULTS: The study population included 148 patients with cervical esophageal cancer from a prospective database of 3445 patients. Primary surgery was the treatment of choice for 56 (37.83%) patients, definitive CRT was the treatment of choice for 52 (35.13%) patients, and CRT followed by surgery was the treatment of choice for 40 (27.02%) patients. CRT-treated patients obtained 36.96% complete clinical response, with overall morbidity and mortality rates of 36.95 and 2.17%, respectively. Surgical complete resection was achieved in 71.88% of surgically treated cases, with morbidity and mortality rates of 52.17 and 6.25%, respectively. No significant survival difference existed among the three treatments, but patients who underwent surgery alone had a significantly lower stage of disease (p = 0.031). Compared with patients with complete response after CRT, surgery did not confer any significant survival benefit, and overall 5-year survival was lower than definitive CRT alone. In contrast, surgery improved survival significantly in patients with non-complete response after definitive CRT (p = 0.023). CONCLUSIONS: Definitive platinum-based CRT should be the treatment of choice for cervical esophageal cancer. Surgery has a role for patients with non-complete response as it adds significant survival benefit, with acceptable morbidity and mortality.

Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival.

Cancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although it is responsible for approximately one-third of cancer deaths, no effective therapies are available and the underlying mechanisms have not been fully elucidated. We previously identified the bromodomain and extra-terminal domain (BET) protein BRD4 as an epigenetic regulator of muscle mass. Here we show that the pan-BET inhibitor (+)-JQ1 protects tumor-bearing mice from body weight loss and muscle and adipose tissue wasting. Remarkably, in C26-tumor-bearing mice (+)-JQ1 administration dramatically prolongs survival, without directly affecting tumor growth. By ChIP-seq and ChIP analyses, we unveil that BET proteins directly promote the muscle atrophy program during cachexia. In addition, BET proteins are required to coordinate an IL6-dependent AMPK nuclear signaling pathway converging on FoxO3 transcription factor. Overall, these findings indicate that BET proteins may represent a promising therapeutic target in the management of cancer cachexia.

Esophageal Cancer Surgery for Patients with Concomitant Liver Cirrhosis: A Single-Center Matched-Cohort Study.

BACKGROUND: Cirrhosis is a risk factor with nonhepatic surgery, but only three series regarding esophagectomy are reported. The Model for End-Stage Liver Disease (MELD) score has shown benefit in risk evaluation, but there is no experience regarding esophagectomy. This study aimed to compare the outcomes of surgery for esophageal cancer between cirrhotic and noncirrhotic patients and to evaluate whether the MELD score has a prognostic value for risk stratification. METHODS: From the authors' esophageal cancer database, they selected all the patients with concomitant cirrhosis who underwent surgery with curative intent and a matched cohort of patients without cirrhosis. The preoperative data included demographics, medical history, blood work, American Society of Anesthesiologists (ASA) score, Child-Turcotte-Pugh (CTP) score, and MELD score. The operative data included type of surgery, radicality, operative time, and blood loss. The postoperative data included hemoderivatives, 90-day morbidity and mortality rates, lab works, and hospital length of stay. The cirrhotic patients were further divided and analyzed according to a MELD score cutoff of 9. RESULTS: Of 3445 esophageal cancer patients, 73 cirrhotic patients underwent surgery. Their 90-day morbidity and mortality rates were higher than those for 146 noncirrhotic patients. The cirrhotic patients also had more respiratory events (p = 0.013) and infections (p = 0.005). The anastomotic complications among the cirrhotic patients were significantly more severe (p = 0.046). No difference in 5-year survival rates was registered. Stratification according to the MELD score showed that patients with a MELD score higher than 9 had a significantly worse postoperative course (5-year survival: p = 0.004). The patients with a MELD score of 9 or lower showed an outcome similar to that of the noncirrhotic patients. CONCLUSIONS: Liver cirrhosis is not an absolute contraindication to esophagectomy. The MELD score can be applicable for esophagectomy risk assessment for cirrhotic patients.

Endoscopic Tumor Length Should Be Reincluded in the Esophageal Cancer Staging System: Analyses of 662 Consecutive Patients.

Esophageal cancer represents the 6th cause of cancer mortality in the World. New treatments led to outcome improvements, but patient selection and prognostic stratification is a critical aspect to gain maximum benefit from therapies. Today, patients are stratified into 9 prognostic groups, according to a staging system developed by the American Joint Committee on Cancer. Recently, trying to better select patients with curing possibilities several authors are reconsidering tumor length as a valuable prognostic parameter. Specifically, endoscopic tumor length can be easily measured with an esophageal endoscopy and, if its utility in esophageal cancer staging is demonstrated, it may represent a simple method to identify high risk patients and an easy-to-obtain variable in prognostic stratification. In this study we retrospectively analyzed 662 patients treated for esophageal cancer, stratified according to cancer histology and current staging system, to assess the possible role of endoscopic tumor length. We found a significant correlation between endoscopic tumor length, current staging parameters and 5-year survival, proving that endoscopic tumor length may be used as a simple risk stratification tool. Our results suggest a possible indication for preoperative therapy in early stage squamocellular carcinoma patients without lymph nodes involvement, who are currently treated with surgery alone.

Oesophageal cancer: assessment of tumour response to chemoradiotherapy with tridimensional CT.

PURPOSE: To investigate whether changes in tumour volume were predictive of histopathological response to neoadjuvant therapy for oesophageal cancer. MATERIALS AND METHODS: Thirty-five consecutive patients with locally advanced oesophageal cancer were treated with chemoradiotherapy and surgery in responders from July 2007 to July 2009. Tumour volume (TV) was calculated using innovative tumour volume estimation software which analysed computed tomography (CT) data. Tumour diameter and area were also evaluated. Variations in tumour measurements following neoadjuvant treatment were compared with the histopathological data. RESULTS: Median baseline tumour diameter, area and volume were 3.51 cm (range 1.67-6.61), 7.51 cm(2) (range 1.79-21.0) and 33.80 cm(3) (range 3.36-101.6), respectively. Differences in TV between the pre- and post-treatment values were significantly correlated with the pathological stage (τ = 0.357, p = 0.004) and the tumour regression grade index (τ = 0.368, p = 0.005). According to the receiver operating characteristic analysis, TV measurements following treatment had moderate predictive values for the pathological T stage (area under the curve, AUC = 0.742, sensitivity = 55.56 %, specificity = 92.86 %, p = 0.005).Comparison of pathological and radiological volume showed a good precision (Pearson rho 0.77). CONCLUSIONS: Changes in TV calculated on CT scans have a limited role in predicting pathological response to neoadjuvant treatment in oesophageal cancer patients. New imaging techniques based on metabolic imaging may provide better results.

Nodal metastasis from locally advanced esophageal cancer: how neoadjuvant therapy modifies their frequency and distribution.

BACKGROUND: Neoadjuvant chemoradiotherapy (CT-RT) before esophagectomy seems to affect the number of nodal metastasis and to alter the distribution of those that remain. The aim of this study was to define how neoadjuvant chemoradiotherapy changes nodal metastasis patterns in locally advanced esophageal cancer. METHODS: A total of 402 consecutive patients with cancer of the esophagus or esophagogastric junction (181 adenocarcinoma [AC] and 221 squamous cell carcinoma [SCC]) (evaluated at clinical stage T1N1, T2N1, T3N0, or T3N1 and pathological stage M0) presenting in our Department between 1992 and 2007 and who underwent complete resection (R0) were included in this retrospective study on a prospectively collected database. All dissected lymph nodes were retrieved and microscopically analyzed. Nodal metastasis patterns in patients who underwent chemotherapy (CT) or chemoradiotherapy (CT-RT) neoadjuvant therapy were compared with those in patients who underwent surgery alone. RESULTS: Almost 30% of the adenocarcinoma patients and approximately 40% of the SCC patients showed effective tumor downstaging after neoadjuvant therapy. There were fewer paracardial node metastases (P = .002) in the AC patients who underwent CT-RT neoadjuvant therapy. There were, likewise, significantly fewer paraesophageal, paracardial, and subcarinal node metastases in the SCC patients in whom the perigastric nodes became the second-most frequent site of metastasis. CONCLUSION: Not only was frequency of lymph node metastases decreased after neoadjuvant therapy, but nodal localization and pattern were also significantly modified.

Interval between neoadjuvant chemoradiotherapy and surgery for squamous cell carcinoma of the thoracic esophagus: does delayed surgery have an impact on outcome?

OBJECTIVE: Aim of this study was to evaluate whether delayed surgery after neoadjuvant chemoradiotherapy (CRT) affects postoperative outcomes in patients with locally advanced squamous cell carcinoma (SCC) of the thoracic esophagus. BACKGROUND: Esophagectomy is usually recommended within 4 to 6 weeks after completion of neoadjuvant CRT. However, the optimal timing of surgery is not clearly defined. METHODS: A total of 129 consecutive patients with locally advanced esophageal cancer, treated between 1998 and 2007, were retrospectively analyzed using prospectively collected data. Patients were divided into 3 groups on the basis of timing to surgery: group 1, ≤30 days (n = 17); group 2, 31 to 60 days (n = 83); and group 3, 61 to 90 days (n = 29). Subsequently, only 2-numerically more consistent-groups were studied, using the median value of timing intervals as a cutoff level: group A, ≤46 days (n = 66); and group B, >46 days (n = 63). RESULTS: Groups were comparable in terms of patient and tumor characteristics, type of neoadjuvant regimen, toxicity, postoperative morbidity and mortality rates, tumor downstaging, and pathologic complete responses. The overall 5-year actuarial survival rate was 0% in group 1, 43.1% in group 2, and 35.9% in group 3 (P = 0.13). After R0 resection (n = 106), the 5-year actuarial survival rate was 0%, 51%, and 47.3%, respectively (P = 0.18). Tumor recurrence after R0 resection seemed to be inversely related, even if not significantly (P = 0.17), to the time interval between chemoradiation and surgery: 50% in group 1, 40.6% in group 2, and 21.7% in group 3. When considering only 2 groups, the overall 5-year survival was 33.1% in group A and 42.7% in group B (P = 0.64); after R0 resection, the 5-year survival was 37.8% and 56.3%, respectively (P = 0.18). The rate of tumor recurrence was significantly lower in group B (25%) than in group A (48.3%) (P = 0.02). CONCLUSION: Delayed surgery after neoadjuvant chemoradiation does not compromise the outcomes of patients with locally advanced SCC of the esophagus. Delaying surgery up to 90 days offers relevant advantages in the clinical management of the patients, can reduce tumor recurrences, and may improve prognosis after complete R0 resection surgery.