BACKGROUND

Despite increasingly radical surgery for esophageal carcinoma, a large number of patients still experience recurrent disease soon after operation. The current study was undertaken to evaluate the pattern of recurrence after curative esophagectomy for cancer of the thoracic esophagus and to identify factors predictive of recurrent disease.



METHODS

A total of 439 consecutive patients discharged from the authors' institution following R0 resection between January 1982 and July 2002 were followed for evidence of recurrence over a mean interval of 37.3 (range, 1–207) months.



RESULTS

Overall 1-, 3- and 5-years survival rates were 91%, 54%, and 41%, respectively. Some 230 patients (52.4%) developed proven recurrence, of whom 24 were alive and 206 were dead at the time of writing. The median time to recurrence was 12.0 (range, 6–96) months, with a median survival thereafter of 7.0 (range, 0–83) months. The pattern of recurrence was local in 12.1%, regional in 20.5% (cervical 3.6%, mediastinal 14.8%, and abdominal 2.1%), and distant in 19.8%, respectively. The overall pattern of dissemination was significantly different according to the histologic subtype (P = 0.021). One hundred five (45.7%) of all recurrences occurred within 12 months of surgery, with local, regional, and distant recurrence occurring at a median of 14.0 (range, 6–77), 13.5 (range, 6–73), and 11.0 (range, 6–96) months, respectively; A factor predictive of recurrent disease was histologic tumor depth invasion (P = 0.001).



CONCLUSIONS

Depth of tumor invasion should be used to identify patients who will have recurrence within 12 months of operation, so that these patients may be either entered into trials of multimodality treatment or offered nonsurgical palliation. Cancer 2003;97:1616–23. © 2003 American Cancer Society.



DOI 10.1002/cncr.11228

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.11228

Pattern of recurrence following complete resection of esophageal carcinoma and factors predictive of recurrent disease

We investigated the cell-death mechanisms induced in esophageal cancer cells in response to the chemotherapeutic drugs, 5-fluorouracil (5-FU) and cisplatin Chemosensitive cell lines exhibited apoptosis whereas chemoresistant populations exhibited autophagy and a morphology resembling type II programmed cell death (PCD) Cell populations that respond with autophagy are more resistant and will recover following withdrawal of the chemotherapeutic agents Specific inhibition of early autophagy induction with siRNA targeted to Beclin 1 and ATG7 significantly enhanced the effect of 5-FU and reduced the recovery of drug-treated cells Pharmacological inhibitors of autophagy were evaluated for their ability to improve chemotherapeutic effect The PtdIns 3-kinase inhibitor 3-methyladenine did not enhance the cytotoxicity of 5-FU Disruption of lysosomal activity with bafilomycin A1 or chloroquine caused extensive vesicular accumulation but did not improve chemotherapeutic effect These observations suggest that an autophagic response to chemotherapy is a survival mechanism that promotes chemoresistance and recovery and that selective inhibition of autophagy regulators has the potential to improve chemotherapeutic regimes Currently available indirect inhibitors of autophagy are, however, ineffective at modulating chemosensitivity in these esophageal cancer cell lines

Induction of autophagy by drug-resistant esophageal cancer cells promotes their survival and recovery following treatment with chemotherapeutics.

Aims: Despite increasingly radical surgery for oesophageal cancer many patients continue to represent with recurrent disease. This study aimed to evaluate the pattern of failure following attempted curative oesophagectomy with mediastinal and upper abdominal lymphadenectomy. METHODS: Some 212 consecutive patients undergoing R0 resection for malignancy between 1 April 1990 and 1 April 1999 were followed up for evidence of recurrence. Clinical evaluation was supported by ultrasonography, computed tomography, isotope scan, endoscopy and laparotomy with biopsy assessment if appropriate. Patients were excluded if recurrence was diagnosed on clinical grounds alone. Statistical analysis was performed using chi2 and log rank tests. RESULTS: Some 142 patients with adenocarcinoma and 70 with squamous carcinoma (SCC) were followed up for a median of 14 (range 1-108) months. Sex and age distribution were similar for both histological subtypes (men : women 3 : 1; median age 64 (30-79) years). Twenty patients died from non-cancer related causes, including 11 (5 per cent) from postoperative complications. Some 89 patients (42 per cent) developed proven recurrent disease of which seven are alive and 82 dead. The median time to recurrence was 11 (2-40) months with a median time to death thereafter of 3 (1-21) months. The pattern of recurrence was locoregional in 23 per cent (oesophageal bed 15 per cent, upper abdominal 3 per cent, upper mediastinal 3 per cent, cervical 2 per cent) and haematogenous in 18 per cent (comprising liver 8 per cent, bone 4 per cent, cerebral 3 per cent, lung 2 per cent, skin 1 per cent) with peritoneal dissemination in 1 per cent. While there was no difference in the overall pattern of dissemination for each histological subtype, the incidence of cervical and upper mediastinal recurrence was significantly higher for adenocarcinoma compared with SCC (chi2 = 5. 9, 1 d.f., P < 0.02). The timing of recurrence was similar for both histological subtypes: 60 per cent of all recurrence occurred within 12 months of surgery, with distant and locoregional recurrence occurring at a median of 10 (2-40) and 11 (2-32) months respectively. CONCLUSIONS: The low incidence of upper mediastinal and cervical recurrence suggests that more extensive lymphadenectomy is unlikely to impact upon survival. Improved staging modalities are required to identify the significant number of patients who develop early recurrence in the first year following surgery in order to offer them multimodality therapies of non-surgical palliation.

Pattern of recurrence following radical oesophagectomy with two-field lymphadenectomy

Background
Over the past 50 years there has been a remarkable change in the epidemiology of esophageal cancer. Previously rare, adenocarcinoma of the esophagus and gastroesophageal junction is now the most common esophageal cancer, and in the United States the incidence is increasing faster than that of any other malignancy. Surveillance in patients with Barrett’s esophagus is identifying adenocarcinoma at an earlier, more curable stage in many patients, and at the same time new endoscopic and surgical options are available for the therapy of these localized tumors.

Adenocarcinoma of the Esophagus and Cardia: A Review of the Disease and Its Treatment

Isolation of tumor cells using size and deformation.

https://www.gastrojournal.org/article/S0016-5085(99)70175-7/pdf

Micrometastases in esophagogastric cancer: High detection rate in resected rib segments

Small cell carcinoma of the oesophagus is an uncommon malignancy. Only 272 cases have been reported to date. Inconsistency in therapeutic approaches reflects the paucity of individual experience and the unsatisfactory response to current management strategies. We report 11 cases drawn from a series of 1012 cases of oesophageal malignancy and perform a statistical analysis on treatment and survival data of 189 cases drawn from the world literature. Small cell carcinoma of the oesophagus was seen to have an incidence of 1%. Seven of 11 patients were female. A variety of therapeutic modalities were employed, and the median survival was 6.6 months. Statistical analysis of these and worldwide data showed a significant survival advantage for patients who received multimodality therapy.

Robert Stuart

Papers

Micrometastases in esophagogastric cancer: High detection rate in resected rib segments

Small cell carcinoma of the oesophagus