Complementary pneumatic dilations are an effective and safe treatment when laparoscopic myotomy fails: A 30-year experience at a single tertiary center.

BACKGROUND: In the last 3 decades, laparoscopic Heller myotomy (LHM) has represented the treatment of choice for esophageal achalasia, solving symptoms in most patients. Little is known about the fate of patients relapsing after LHM or their treatment. In this study, we aimed at evaluating the results of complementary pneumatic dilations (CPDs) after ineffective LHM. METHODS: We evaluated the patients who underwent LHM with Dor fundoplication (LHD) from 1992 to 2022 and were submitted to CPD for persistent or recurrent symptoms. The patients were followed clinically and with manometry, barium swallow, and endoscopy when necessary. An Eckardt score (ES) of > 3 was used as threshold for failure. RESULTS: Of 1420 patients undergoing LHD, 120 (8.4%) were considered failures and were offered CPD. Ten patients refused further treatment; in 5 CPD was not indicated for severe esophagitis; 1 patient had surgery for a misshaped fundoplication and 1 patient developed cancer 2 years after LHD; that leaves 103 patients who underwent a median 2 CPDs (IQR, 1-3), at a median of 15 (IQR, 8-36) months after surgery, with 3.0- to 4.0-cm Rigiflex dilator (Boston Scientific, Massachusetts, USA). No perforations were recorded. Only 6 patients were lost to follow-up. Thus, 97 were followed for a median of 37 months (IQR, 6-112) after the last CPD: 70 (72%) were asymptomatic, whereas 27 (28%) had significant persistent dysphagia (ES > 3). The only differences between the 2 groups were the ES after surgery (P < .01) and the number of required CPD. Overall, the combination of LHD + CPD provided a satisfactory outcome in 96.5% of the patients. CONCLUSION: CPDs represent an effective and safe option to treat patients after a failed LHD: when the postsurgery ES consistently remains high and the number of CPDs required to control symptoms exceeds 2, this may suggest the need for further invasive treatments.

Short- and Long-Term Outcomes in Elderly Patients with Resectable Esophageal Cancer: Upfront Esophagectomy Compared to Surgery after Neoadjuvant Treatments.

Background/Objectives: Despite the increased incidence of esophageal cancer (EC) in elderly people, there are no clear guidelines for its treatment in these patients. The aim of this study was to compare the outcomes of patients ≥ 75 years with resectable EC, receiving either upfront esophagectomy or neoadjuvant treatment. Methods: We retrospectively identified 127 patients with resectable EC ≥ 75 years who underwent esophagectomy between January 2000 and December 2022 at our Clinic in the University Hospital of Padova. The included patients were stratified into two groups: patients undergoing upfront esophagectomy (SURG group) and patients receiving neoadjuvant treatment (NAT group). Results: There were no statistically significant differences in OS (p = 0.7708), DFS (p = 0.7827) and cancer-related survival (p = 0.0827) between the SURG and the NAT group, except for the OS of EAC with stage III-IV, where the NAT group experienced a significant benefit in OS (p = 0.0263). When comparing the two groups, patients receiving neoadjuvant treatment experienced a significantly higher rate of postoperative complications (p = 0.0266). At univariate analysis, neoadjuvant therapy was the only variable strongly associated with postoperative morbidity (p = 0.026). Conclusions: Considering the unique characteristics of elderly patients, the choice of a multimodal approach should be tailored to each case in a multidisciplinary setting and balanced with a potential higher risk of postoperative complications, as well as potential toxicity related to chemoradiation and reduced life expectancy.

The esophageal pull-down technique improves the outcome of laparoscopic Heller-Dor myotomy in end-stage achalasia.

BACKGROUND: The treatment of patients with end-stage achalasia with a sigmoid-shaped esophagus is particularly challenging. A modified technique (pull-down technique) has been developed to straighten the esophageal axis, but only a limited number of studies on this topic are available in the literature. This study aimed to compare the outcome of patients who underwent the pull-down technique with that of patients who had a classical laparoscopic Heller-Dor (CLHD) myotomy. METHODS: All patients with a radiologic diagnosis of end-stage achalasia who underwent an LHD myotomy between 1995 and 2022 were considered eligible for the study. All patients underwent symptom score, barium swallow, endoscopy, and manometry tests before and after the procedure was performed. Treatment failure was defined as the persistence or reoccurrence of an Eckardt score (ES) of >3 or the need for retreatment. RESULTS: Of the 94 patients who were diagnosed with end-stage achalasia (male-to-female ratio of 52:42), 60 were treated with CLHD myotomy, and 34 were treated with the pull-down technique. Of note, 2 patients (2.1%), both belonging to the CLHD myotomy group, developed a squamous cell carcinoma during the follow-up. The overall success of LHD myotomy was seen in 76 of 92 patients (82.6%). All patients in both groups achieved a lower ES after surgery. The failure rates were 27.6% (16/58) in the CLHD myotomy group and 5.9% (2/34) in the pull-down technique group (P < .01). CONCLUSION: Our findings confirm that LHD myotomy is an effective treatment of end-stage achalasia and that the pull-down technique further improves the outcome in patients with end-stage achalasia who are difficult to treat.

Manometric identikit of a functioning and effective fundoplication for gastroesophageal reflux disease in the high-resolution manometry ERA.

BACKGROUND: The pathophysiological and clinical value of performing High-Resolution Manometry (HRM) after laparoscopic fundoplication (LF) for gastroesophageal reflux disease (GERD) is still unclear and debated. OBJECTIVE: We sought to establish the HRM parameters indicative of functioning fundoplications, and whether HRM could distinguish them from tight or defective ones. METHODS: The study involved patients with GERD who underwent laparoscopic Nissen (LN) or Toupet (LT) fundoplication between 2010 and 2022. HRM and 24-h pH monitoring were performed before and 6 months after surgery. The study population was divided into 5 groups: LN and LT patients with normal 24h-pH findings (LNpH- and LTpH-, respectively); LN and LT patients with pathological 24h-pH findings (LNpH+ and LTpH + groups, respectively); and patients with a postoperative dysphagia intensity score >2 (Dysphagia group). The novel Hiatal Morphology (HM) classification was applied, envisaging 3 different subtypes: HM1 (normal), HM2 (intrathoracic fundoplication), and HM3 (slipped fundoplication). RESULTS: Among the 132 patients recruited during the study period, 46 were in the LNpH- group, 51 in the LTpH- group, 15 in the LNpH + group, 7 in the LTpH + group, and 5 in the Dysphagia group. In multivariate analysis, postoperative abdominal lower esophageal sphincter length (p = 0.001) and HM2 (p < 0.001) were both independently associated with surgical failure. Integrated relaxation pressure was significantly higher in the Dysphagia group than in the LNpH- group. CONCLUSION: This study generated reference HRM values for an effective LF, and confirms that using HRM to assess the neo-sphincter and HM improves the clinical assessment in cases of symptom recurrence.

Paraneoplastic myopathy-related rhabdomyolysis and pancreatic cancer: A case report and review of the literature.

BACKGROUND: Rhabdomyolysis is a life-threatening condition, often leading to progressive renal failure and death. It is caused by destruction of skeletal muscle and the release of myoglobin and other intracellular contents into the circulation. The most frequent cause of this condition is "crush syndrome", although several others have been described and paraneoplastic inflammatory myopathies associated with various types of cancer are repeatedly reported. CASE SUMMARY: We describe a rare case of a patient with pancreatic cancer who developed rhabdomyolysis early on, possibly due to paraneoplastic myositis leading to acute renal failure and eventually to rapid death. A 78-year-old Caucasian woman was referred to our hospital for obstructive jaundice and weight loss due to a lesion in the pancreatic head. She presented increasingly severe renal insufficiency with anuria, a dramatic increase in creatine phosphokinase (36000 U/L, n.v. 20-180 U/L) and myoglobin (> 120000 µg/L, n.v. 12-70 µg/L). On clinical examination, the patient showed increasing pain in the lower limbs associated with muscle weakness which was severe enough to immobilize her. Paraneoplastic myopathy linked to the malignant lesion of the pancreatic head was suspected. The patient was treated with hemodialysis and intravenous methylprednisolone. Despite all the efforts to prepare the patient for surgery, her general condition rapidly deteriorated and she eventually died 30 d after hospital admission. CONCLUSION: The possible causes of rhabdomyolysis in this patient with pancreatic cancer are discussed, the development of paraneoplastic myopathy being the most likely. Clinicians should bear in mind that these syndromes may become clinically manifest at any stage of the cancer course and their early diagnosis and treatment could improve the patient's prognosis.

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.

NAD+ repletion with niacin counteracts cancer cachexia.

Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD+ repletion therapy in cachectic mice reveals that NAD+ precursor, vitamin B3 niacin, efficiently corrects tissue NAD+ levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose NAD+ metabolism as a therapy target for cachectic cancer patients.

Safety and Efficacy of Surgery for Metastatic Tumor to the Pancreas: A Single-Center Experience.

Pancreatic metastases from other neoplasms are rare. The role of surgery for this clinical entity is unclear. The aim of this study was to investigate the role of resection in patients with pancreatic secondary lesions. We observed 44 patients with pancreatic metastases from other tumors. Renal cell carcinoma was the most common primary tumor (n = 19, 43.2%). Thirty-seven patients underwent surgery, and pancreatic resection with curative intent was feasible in 35 cases. Fifteen patients (43.2%) experienced major postoperative complications (Clavien-Dindo > 2), and postoperative mortality rate was 5.4%. The median overall survival and disease-free survival were 38 (range 0-186) and 11 (range 0-186) months, respectively. Overall survival and disease-free survival were significantly longer for pancreatic metastases from renal cell carcinoma when compared to other primary tumors. Multivariate analysis confirmed a pathological diagnosis of metastasis from RCC as an independent prognostic factor for overall survival (OR 2.48; 95% CI, 1.00-6.14; p = 0.05). In conclusion, radical resection of metastases to the pancreas is feasible and safe, and may confer a survival benefit for selected patients. There is a clear benefit of metastasectomy in terms of patient survival for metastases from renal cell carcinoma, while for those with other primary tumors, surgery seems to be mainly palliative.

Transoral septotomy with septum traction is an effective treatment for recurrent Zenker diverticulum.

Symptoms of Zenker diverticulum can recur whatever the type of primary treatment administered. A modified transoral stapler-assisted septotomy (TS) was introduced in clinical practice a few years ago to improve the results of this mini-invasive technique. The aim of this prospective, controlled study was to assess the outcome of TS in patients with recurrent Zenker diverticulum (RZD), as compared with patients with treatment-naïve Zenker diverticulum (NZD). Patients diagnosed with NZD or RZD, and treated with TS between 2015 and 2021 were compared. Symptoms were recorded and scored using a detailed questionnaire. Barium swallow and endoscopy were performed before and after the TS procedure. In sum, 89 patients were enrolled during the study period: 68 had NZD and 21 had RZD. The patients' demographic and clinical data were similar in the two groups. Three mucosal lesions were detected intra-operatively, and one came to light at post-operative radiological assessment in the NZD group. No mucosal lesions were detected in the RZD group. The median follow-up was 36 months (interquartile range 23-60). The treatment was successful in 97% NZD patients and 95% of RZD patients (P = 0.56). This is the first comparative study based on prospectively collected data to assess the outcome of TS in patients with RZD. Traction on the septum during the procedure proved effective in the treatment of RZD, achieving a success rate that was excellent, and comparable with the outcome in treating NZD.

Laparoscopic Heller-Dor is an effective long-term treatment for end-stage achalasia.

BACKGROUND: The end-stage achalasia is a difficult condition to treat, for the esophageal diameter and conformation of the gullet, that may progress to a sigmoid shape. The aim of this study was to examine the outcome of Laparoscopic Heller-Dor in patients with end-stage achalasia, comparing them with patients who had mega-esophagus without a sigmoid shape. METHODS: From 1992 to 2020, patients with a diagnosis of sigmoid esophagus, or radiological stage IV achalasia (the SE group), and patients with a straight esophagus larger than 6 cm in diameter, or radiological stage III achalasia (the NSE group), were all treated with LHD. The two groups were compared in terms of patients' symptoms, based on the Eckardt score, and on barium swallow, endoscopy and manometry performed before and after the treatment. The failure of the treatment was defined as an Eckardt score > 3, or the need for further treatment. RESULTS: The study involved 164 patients: 73 in the SE group and 91 in the NSE group. No intra- or postoperative mortality was recorded. The median follow-up was 51 months (IQR 25-107). The outcome was satisfactory in 71.2% of patients in the SE group, and in 89% of those in the NSE group (p = 0.005). CONCLUSIONS: SE is certainly the worst condition of the disease and the final outcome of LHD, in term of symptom control, is inferior compared to NSE. Despite this, almost 3/4 of the SE patients experienced a significant relieve in symptoms after LHD, which may therefore still be the first surgical option to offer to these patients, before considering esophagectomy.

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.

Does Pancreatic Fistula Affect Long-Term Survival after Resection for Pancreatic Cancer? A Systematic Review and Meta-Analysis.

BACKGROUND: The impact of postoperative pancreatic fistula (POPF) on survival after resection for pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: The MEDLINE, Scopus, Embase, Web of Science, and Cochrane Library databases were searched for studies reporting on survival in patients with and without POPF. A meta-analysis was performed to investigate the impact of POPF on disease-free survival (DFS) and overall survival (OS). RESULTS: Sixteen retrospective cohort studies concerning a total of 5019 patients with an overall clinically relevant POPF (CR-POPF) rate of 12.63% (n = 634 patients) were considered. Five of eleven studies including DFS data reported higher recurrence rates in patients with POPF, and one study showed a higher recurrence rate in the peritoneal cavity. Six of sixteen studies reported worse OS rates in patients with POPF. Sufficient data for a meta-analysis were available in 11 studies for DFS, and in 16 studies for OS. The meta-analysis identified a shorter DFS in patients with CR-POPF (HR 1.59, p = 0.0025), and a worse OS in patients with POPF, CR-POPF (HR 1.15, p = 0.0043), grade-C POPF (HR 2.21, p = 0.0007), or CR-POPF after neoadjuvant therapy. CONCLUSIONS: CR-POPF after resection for PDAC is significantly associated with worse overall and disease-free survival.

Recent Advances in Pancreatic Neoplasms.

Pancreatic neoplasms, both primary and secondary, include different pathological entities with variable biological behavior and, consequently, different treatment modalities [...].

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.