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Ann Thorac Surg 2000;69:205-209
© 2000 The Society of Thoracic Surgeons

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Original Articles

What is the optimal distal resection margin for esophageal carcinoma?

^a Regional Department of Thoracic Surgery, Heartlands Hospital, Birmingham Clinical Trials Unit, CRC Institute for Cancer Studies, Birmingham, United Kingdom

Address reprint requests to Dr Casson, Division of Thoracic Surgery, QEII Health Sciences Centre, Victoria Building 7S-008, 1278 Tower Rd, Halifax, NS B3H 2Y9, Canada
e-mail: thoracic{at}dal.ca

Presented at the Poster Session of the Thirty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 25–27, 1999.

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. Whereas a proximal resection margin of 12 cm is recommended for complete resection of esophageal cancer, the extent of distal resection is unclear.

Methods. We examined distal resection margins in a consecutive series of patients who underwent esophagectomy for squamous cell carcinomas (n = 50), primary esophageal adenocarcinomas (n = 100), and adenocarcinomas of the cardia (n = 39), in whom all macroscopic tumor was judged to be completely resected.

Results. Microscopic tumor was found at a 3-cm distal resection margin for one multifocal squamous cell carcinoma. Positive distal resection margins were seen in 12% (12 of 100 patients) of primary esophageal adenocarcinomas (median, 2 cm versus 4 cm if negative; p = 0.002, Wilcoxon) and 28% (11 of 39 patients) of cardia adenocarcinomas (median, 1 cm versus 3 cm if negative; p = 0.02, Wilcoxon). Although pathologic stage was shown to be the only significant predictor of overall survival (Hazard ratio [HR] 1.8; 95% confidence interval 1.2 to 2.6; p = 0.007), there was a trend toward reduced postoperative survival for patients with histologically positive distal resection margins, in particular for patients with cardia adenocarcinomas (median, 15.4 months versus 5.7 months if negative; p = 0.0001).

Conclusions. To achieve consistently negative distal resection margins, we recommend resection of at least 5 cm of macroscopically normal foregut below the distal margin of the primary tumor.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
Despite recent advances in multimodality therapy, the prognosis for invasive esophageal carcinoma is generally poor [1, 2]. This has been attributed, at least in part, to an aggressive tumor biology, late presentation, and advanced tumor stage. However, one consistent determinant of long-term survival for locoregional disease is completeness of surgical resection [3–5].

It is generally accepted that the microscopic spread of esophageal cancer is usually far more extensive than the macroscopic boundaries of the tumor. Longitudinal spread of tumor cells, especially proximally, is thought to be facilitated by the extensive submucosal lymphatic network within the tubular esophagus. To date, most studies have evaluated only the proximal spread of esophageal squamous cell carcinoma [6–10]. In one early and widely referenced study, microscopic tumor was found in 3% of patients 10.5 cm proximal to the visible tumor [6], leading to the recommendation that 12 cm of macroscopically normal esophagus above the upper border of the primary tumor should be resected to obtain an adequate excision.

The epidemiology of foregut (ie, esophageal and gastric) malignancy has changed dramatically during the past two decades [11–13]. Although several recent reports have evaluated the extent of proximal (esophageal) spread of adenocarcinomas of the cardia and upper third of the stomach [14–17], few studies have critically addressed the significance of circumferential (radial) [18] or distal resection margin involvement [19].

The aim of this study was to examine the extent of distal resection for carcinomas of the esophagus and cardia. Microscopic tumor spread below the inferior limit of the primary tumor was characterized histologically at the distal resection margin, and correlated with selected clinicopathologic features, tumor stage, and outcome. It was anticipated that these observations would provide a rational basis for recommending the extent of the distal resection for esophageal and cardia carcinomas.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
The study population comprised 189 sequentially accrued patients (133 men, 56 women) who underwent resection of esophageal and cardia carcinomas at Birmingham Heartlands Hospital (a regional department of thoracic surgery, West Midlands, United Kingdom) between February 1990 and July 1998. No patient received preoperative chemotherapy or radiotherapy. For all patients in this series, regardless of tumor histology, a total thoracic esophagectomy was performed using a left thoracoabdominal approach. All macroscopic tumor was judged to be completely excised, although frozen section examination of resection margins was not routinely performed intraoperatively. The lesser curve of the stomach with associated nodal and fatty tissue was resected en bloc. The gastric tube was positioned in the posterior mediastinum, and using a left neck incision, the tip of the fundus anastomosed (end-to-end) to the cervical esophagus. The details of the operative procedure are described in detail elsewhere [20].

Immediately after esophageal resection, while still in the operating room, each esophageal specimen was pinned to a cork board, photographed and measured while fresh. To ensure consistency of technique, this was performed according to a standard protocol on all occasions by one investigator (S.J.D.). The distal resection margin was measured in centimeters from the inferior margin of visible tumor, to the level of distal transection of esophagus or stomach. Where the margin was irregular in length, the closest point to the tumor was studied.

All specimens were fixed in formalin and processed according to standard protocols in the Department of Pathology. Representative sections were stained with hematoxylin and eosin and examined by a consultant histopathologist. Tumors were staged according to the 1987 UICC (Union Internationale Contre Le Cancer [International Union Against Cancer]) classification based on pTNM subsets. The distal resection margin was considered positive if tumor cells were present in any layer of the esophageal or gastric mucosa.

Three groups of patients were defined based on tumor histology: group I, patients with esophageal squamous cell carcinomas (n = 50); group II, patients with primary esophageal adenocarcinomas (n = 100); and group III, patients with adenocarcinomas of the cardia (n = 39). Strict clinicopathologic criteria [21] were used to define adenocarcinomas of primary esophageal origin (group II), as follows: the presence of associated Barrett’s epithelium (columnar epithelium-lined esophagus extending more than 3 cm above the esophagogastric junction, or the presence of specialized "intestinal-type" epithelium); more than 75% of the tumor mass involving the tubular esophagus; minimal gastric involvement; direct invasion of periesophageal tissues histologically; and clinical symptoms of esophageal obstruction (dysphagia). Routine clinicopathologic data were measured cross-sectionally. Survival times were calculated as the date of operation to date of death, or date of censor if alive (outcome, overall survival). Statistical analysis was carried out independently (LH) using SAS statistical software (SAS Institute, Cary, NC). Kruskal-Wallis and Wilcoxon tests were used to evaluate differences in distance of resection margins (positive and negative) between tumor groups. Survival curves for tumor histology, stage, and distal resection margin status were constructed by the method of Kaplan and Meier and compared using the log-rank test [22, 23]. Cox proportional hazards analysis was performed to determine important prognostic factors of survival [24].

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
Table 1 summarizes distal resection margin measurements for each group. Significant differences in the extent of distal resection (measured in centimeters from the inferior margin of visible tumor to the nearest point of the distal resection margin in the fresh specimen) were found between groups (p = 0.0001), with median distances of 7, 4, and 1.5 cm for groups I, II, and III, respectively.

Table 2 summarizes tumor histology, stage, and distal resection margin status in terms of survival for all study patients. The median survival for all patients was 13.4 months (Fig 1A), but was significantly reduced for advanced stage tumors (Fig 1B). Although there was a trend toward improved survival for all patients with negative (disease-free) distal resection margins (Fig 2), this did not reach statistical significance (median, 13.6 months versus 10.5 months if positive; p = 0.17). After performing a Cox proportional hazards analysis, only stage was shown as a significant predictor of overall survival, with a hazard ratio of 1.8, showing an increased risk of death with higher stage tumors (95% confidence interval 1.2 to 2.6).

View larger version (13K): [in this window] [in a new window]   Fig 1. (A) Overall survival for all patients. (B) Overall survival for all patients by stage. From top to bottom, stage I (upper solid black line); stage IIA/B (upper short broken line); stage III (alternating dash/dots); stage IV (lower long broken line).

View larger version (10K): [in this window] [in a new window]   Fig 2. Overall survival for all patients by distal resection margin status. Patients with histologically positive distal resection margins (n = 24; solid line) had a trend toward reduced survival (p = 0.17, not significant) compared to patients with negative margins (n = 165; broken line).

	Comment

Top Abstract Introduction Patients and methods Results Comment References

A standard operative approach [20] was used for all patients (regardless of tumor histology) at a single institution during 7.5 years. As frozen section examination was generally not available to confirm or exclude the presence of microscopic tumor at the resection margin, the extent of distal resection was evaluated operatively by inspection and palpation of the primary tumor in situ. Although no in situ measurements were taken, all macroscopic tumor, particularly at the distal resection margin, was judged by the operating surgeon to be completely resected. To reflect this operative decision, all measurements were made on fresh specimens immediately after resection, thereby avoiding shrinkage of tissues associated with fixation in formalin.

We found that the extent of distal resection varied significantly according to tumor histology, which would be anticipated as only one operative approach was used to resect all tumors. The length of distal resection was greatest for squamous cell carcinomas of the esophagus. Microscopic tumor was found in only one specimen (2%) with a macroscopically normal resection margin 3 cm from the distal edge of the main tumor mass. Serial sectioning of the entire specimen suggested a multifocal origin for this squamous cell carcinoma. To date, only one study has evaluated distal (gastric) involvement after esophagectomy for squamous cell carcinoma [19]. Although an 8% rate of gastric wall involvement was identified (by direct invasion; intramural or intraepithelial spread; metastasis to perigastric lymph nodes), no distal measurements were reported.

The extent of distal resection was significantly less for adenocarcinomas of the lower esophagus (group II) and cardia (group III), with median lengths of 4 cm and 1.5 cm, respectively. This would be expected as only one operative approach was used to resect all tumors; the more distal tumors having lesser distal resections. Microscopic tumor was found at the distal resection margin in 12% of primary esophageal adenocarcinomas (group II). Although the extent of distal resection was significantly less than for patients with negative distal resection margins, this did not appear to influence survival. As in other large series of primary esophageal adenocarcinomas [3–5], tumor stage was identified as a significant predictor of survival, both by univariate and multivariate analysis.

Twenty-eight percent of patients with adenocarcinomas of the cardia (group III) had positive distal resection margins. For these, both the extent of distal resection (median, 1 cm) and survival (median, 5.7 months) were significantly shorter compared to patients with histologically negative margins (median, 3 cm and 15.4 months, respectively). As most patients (69%) in this group had stage III tumors, survival by stage was not found to be statistically significant.

Unfortunately, the current terminology defining adenocarcinomas at the esophagogastric junction is inconsistent. One recently proposed classification [25] is based on the anatomic location of the tumor mass: cardia cancers defined as tumors whose center lies within 2 cm of the anatomic esophagogastric junction. As most tumors in this series were advanced stage, often obscuring the esophagogastric junction, such measurements were difficult to obtain. Therefore, we used strict clinicopathologic criteria [21] to distinguish adenocarcinomas of primary esophageal origin (group II) from those arising at the gastric cardia (group III).

It is essential to clearly differentiate primary esophageal adenocarcinomas from adenocarcinomas of the cardia and proximal stomach, as each tumor type appears to have different biological and clinical features [4, 5, 15, 21]. Although the extent of surgical resection for adenocarcinomas of the lower esophagus and cardia is controversial, different surgical approaches to each tumor, particularly with regard to the extent of distal resection, would seem reasonable. This hypothesis is supported by findings from this study where, using only one surgical approach, distal resection margins for cardia adenocarcinomas were shorter, with a higher percentage of positive margins and reduced survival, compared with primary esophageal adenocarcinomas. To achieve consistently negative distal resection margins we recommend resection of a minimum of 5 cm of macroscopically normal foregut below the distal margin of the primary tumor, or alternatively, routine use of frozen section examination.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

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