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PURPOSE Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent ( P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.

Item does not contain fulltext BACKGROUND: Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months' follow-up. In this Article, we report the long-term results after a minimum follow-up of 5 years. METHODS: Patients with clinically resectable, locally advanced cancer of the oesophagus or oesophagogastric junction (clinical stage T1N1M0 or T2-3N0-1M0, according to the TNM cancer staging system, sixth edition) were randomly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy (intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m(2) of body-surface area] for 23 days) with concurrent radiotherapy (41.4 Gy, given in 23 fractions of 1.8 Gy on 5 days per week) followed by surgery, or surgery alone. The primary endpoint was overall survival, analysed by intention-to-treat. No adverse event data were collected beyond those noted in the initial report of the trial. This trial is registered with the Netherlands Trial Register, number NTR487, and has been completed. FINDINGS: Between March 30, 2004, and Dec 2, 2008, 368 patients from eight participating centres (five academic centres and three large non-academic teaching hospitals) in the Netherlands were enrolled into this study and randomly assigned to the two treatment groups: 180 to surgery plus neoadjuvant chemoradiotherapy and 188 to surgery alone. Two patients in the neoadjuvant chemoradiotherapy group withdrew consent, so a total of 366 patients were analysed (178 in the neoadjuvant chemoradiotherapy plus surgery group and 188 in the surgery alone group). Of 171 patients who received any neoadjuvant chemoradiotherapy in this group, 162 (95%) were able to complete the entire neoadjuvant chemoradiotherapy regimen. After a median follow-up for surviving patients of 84.1 months (range 61.1-116.8, IQR 70.7-96.6), median overall survival was 48.6 months (95% CI 32.1-65.1) in the neoadjuvant chemoradiotherapy plus surgery group and 24.0 months (14.2-33.7) in the surgery alone group (HR 0.68 [95% CI 0.53-0.88]; log-rank p=0.003). Median overall survival for patients with squamous cell carcinomas was 81.6 months (95% CI 47.2-116.0) in the neoadjuvant chemoradiotherapy plus surgery group and 21.1 months (15.4-26.7) in the surgery alone group (HR 0.48 [95% CI 0.28-0.83]; log-rank p=0.008); for patients with adenocarcinomas, it was 43.2 months (24.9-61.4) in the neoadjuvant chemoradiotherapy plus surgery group and 27.1 months (13.0-41.2) in the surgery alone group (HR 0.73 [95% CI 0.55-0.98]; log-rank p=0.038). INTERPRETATION: Long-term follow-up confirms the overall survival benefits for neoadjuvant chemoradiotherapy when added to surgery in patients with resectable oesophageal or oesophagogastric junctional cancer. This improvement is clinically relevant for both squamous cell carcinoma and adenocarcinoma subtypes. Therefore, neoadjuvant chemoradiotherapy according to the CROSS trial followed by surgical resection should be regarded as a standard of care for patients with resectable locally advanced oesophageal or oesophagogastric junctional cancer. FUNDING: Dutch Cancer Foundation (KWF Kankerbestrijding).

Objectives: We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT.Background: Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. Methods: Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups.Results:One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgeryalone arm (hazard ratio per 10 additionally resected nodes, 0.76; P = 0.007), but not in the multimodality arm (hazard ratio 1.00; P = 0.98). Conclusions: The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

BACKGROUND. As an alternative to surgical resection, endoscopic treatment modalities are being explored for the treatment of patients with early esophageal carcinoma. This study aimed to evaluate patterns of local growth and regional dissemination of early adenocarcinoma of the esophagus or esophagogastric junction, as these pathologic features may contribute to rational therapeutic decision making. METHODS. Among 173 patients who underwent esophageal resection for invasive adenocarcinoma (1993‐1998), 32 (19%) had early stage cancer (pT1). Clinical records, pathology reports, and original slides of the surgically resected esophagus were reviewed in each case. RESULTS. In 12 patients tumor invasion was limited to the mucosa, whereas in 20 patients the tumor showed infiltration of the submucosa. All cancers were associated with intestinal metaplasia. Areas of high grade dysplasia accompanied 27 of the 32 cancers (84%). Intramucosal cancer had no lymph node metastasis but presented as multifocal disease in 42% of cases and extended under preexisting squamous mucosa in 17% of cases. In submucosal cancer, lymph node metastases were present in 30% of cases. Disease specific 3-year survival for patients with intramucosal cancer was 100% and for those with submucosal cancer 82% (P 5 not significant). CONCLUSIONS. Based on the local growth pattern of intramucosal adenocarcinoma of the esophagus or esophagogastric junction, endoscopic treatment of patients with this disease should be applied with caution. For submucosal carcinoma, surgery is the mainstay of treatment, as lymph node metastasis is frequently present. Both subclassifications of early cancer show a favorable outcome after esophagectomy. Cancer 2000;88:2429 ‐37. © 2000 American Cancer Society.

BACKGROUND Hospital mortality after esophagectomy has decreased from 29% to 7.5% over the last decades because of improved surgical techniques and better perioperative care. Suggestions have been made that a further decrease in hospital mortality may be achieved by centralization of esophagectomies in high volume centers. METHODS The effect of hospital volume on hospital mortality after esophagectomy in the Netherlands was analyzed based on data from the Dutch National Medical Registry and the Dutch Network and National Database for Pathology over the period 1993–1998. RESULTS Annually, approximately 310 (range, 264–321) esophagectomies are performed in the Netherlands. Fifty-two percent are performed in 43–55 low volume centers (1–10 resections a year). Six percent are performed in 1–3 medium volume centers (11–20 resections a year). The remainder (42%) is performed in two high volume centers (> 50 resections a year). Hospital mortality is 12.1%, 7.5% and 4.9% respectively (P < 0.001). The high volume centers seem to see slightly more advanced tumors than the low and medium volume centers. CONCLUSIONS There is a significant (inverse) relation between hospital mortality and hospital volume for esophageal resection in the Netherlands. Although hospital mortality is not the only measure for quality of care, these data suggest a potential beneficial effect to centralization of esophagectomy in the Netherlands. Cancer 2001;91:1574–8. © 2001 American Cancer Society.

To compare UW-solution (UW) and Euro-Collins (EC) for long-term liver preservation we investigated the morphology and metabolic capacity of rat liver after 18 and 42-hours cold-storage in either UW or EC.After harvesting the rat liver was transferred to a perfusion chamber where it was perfused for 10 min with UW or EC at 4°C. Thereafter livers were stored at 4°C in UW or EC for 18 hours (both groups n = 6) or for 42 hours (both groups n = 8). After 18-hr or 42-hr cold-storage a 2-hr warm perfusion (37°C) was started with Krebs-Ringer solution with carbogen to which 125Iodine-triiodothyronine (T3) was added. Control livers (n = 8) were immediately perfused with Krebs-Ringer without cold-storage. The following parameters were assessed: ASAT-levels in the perfusate, T3-metabolites in the bile and the perfusate, the perfusion pressure, the volume of bile secreted and light-microscopical morphology at the end of the warm perfusion period.After cold storage in UW-solution the ASAT-levels in the perfusate were lower than after storage in EC as well as the perfusion pressures. These livers demonstrated a better T3-metabolism and secreted more bile than EC-stored livers. Histological examination showed more tissue damage in the EC-stored livers than in the UW stored livers.We conclude that cold-storage of rat liver in UW-solution resulted in a better morphology and metabolic capacity as compared with EC-solution.