The type of esophagectomy following chemoradiotherapy is decided according to the location and local extension of the tumor in the esophagus, postoperative reflux, extent of lymphadenectomy and surgeon’s preference. In our clinic, esophagectomy routinely starts with a right thoracic approach, and is completed by a median laparotomy and cervical esophagogastrostomy via a left neck incision in the same session[8]. In this study, we represent our experience with transthoracic esophagectomy and cervical esophagogastrostomy following neoadjuvant/ curative chemoradiation.

One patient underwent cervical mediastinoscopy due to a pathologic size left lower paratracheal lymph node. The pathology was benign and patient was assigned for neoadjuvant treatment due to T stage of the tumor (Figure 1).

Fig 1: The tumor in the esophagus was completely invading the esophageal wall in the initial evaluation

Technique of neoadjuvant and curative concurrent chemoradiotherapy
Radiotherapy was administered with 6 or 15 MV photons, in supine position with parallel opposed, anterior and posterior fields. Patients received 46 Gy of radiation with 2 Gy daily fractions, 5 times a week. For simulation process, pretreatment tomographic scans, endoscopic findings and barium swallow graphs were used. Treatment fields were planned to include at least 5 cm of distal and proximal ends of the tumor with 2 cm radial margins. For lymph node coverage, radiation fields also included one level above and one level below situated lymphatic regions, beside the coverage of the lymphatic region where the tumor is situated.

Concurrent with radiotherapy, cisplatin (40 mg/m2 per week) was administered weekly starting with the first day of radiation and continued throughout the whole radiation treatment duration. UFT 300 mg/m2 was administered orally, divided in two daily doses, for five days from Monday to Friday, starting on the first day, and ending on the last day of radiation. All patients were planned to undergo surgical resection 4-8 weeks after the completion of concurrent chemoradiotherapy.

Some patients received curative radiation dose of 50 Gy and cisplatin due to their rejection of surgery as the primary treatment.

Preoperative evaluation
All patients underwent clinical re-staging with upper GI endoscopy, thoracic and upper abdominal CT scans after neoadjuvant treatment. Additionally, 5 patients had upper abdominal ultrasonography, 4 had bone scans and 1 had an upper GI endoscopic ultrasonography. 4 patients who had PET scan did not undergo bone scans and upper abdominal ultrasonography. Patients who had stable or regressed tumor that were amenable for surgical resection and patients who gave consent for surgery underwent resection.

Other than routine radiologic and biochemical investigations, all patients underwent pulmonary function tests, electrocardiography and echocardiography to assess ventricular ejection fractions.

Technique of surgical resection[8]
Right thoracic exploration was performed in left lateral decubitus position in all patients. Thoracic esophagus was mobilized from diaphragmatic hiatus to sternoclavicular junction en bloc with neighboring lymph nodes in 8 patients via right thoracoscopy. Thoracoscopic mobilization of the esophagus was attempted in 2 patients, but a thoracotomy was performed in one of them due to dense fibrotic adhesions between esophagus and posterior pericardium. All patients then underwent a median laparotomy and left cervical incision. A 4-5 cm wide great curvature tube supplied by right gastroepiploic artery was prepared from the stomach. Following transection of the esophagus in the cervical area the esophagectomy and proximal gastrectomy specimen was delivered from the abdomen and great curvature tube was anastomosed to the remaining esophagus in the left cervical area. Gastroesophageal anastomosis was performed on the posterior wall of the conduit with full thickness separate 3/0 silk sutures. Heineke-Mikulicz pyloroplasty was performed in the first 3 patients and no pyloric drainage procedure was performed in the last 7 patients. Feeding jejunostomy was placed in 7 patients at the same session.

Oral intake was started on postoperative day 7 following a control barium swallow study. Patients were scheduled for follow-up every 3 months in the first 2 years and every 6 months afterwards.

Four patients had comorbidities prior to surgery. Two patients over the age of 70 had prior cerebrovascular accident. One of them had diabetes and the other hypertension. Two patients had diffuse pleural adhesions and plaques due to previous tuberculosis infection. Median preoperative weight of the patients was 53 kg (40–63). Patients were ex-smokers (n=7), never-smokers (n=2) and active smokers (n=1). Average FEV1 was 83±22%.

In 5 patients, radiologic response was observed following neoadjuvant treatment (Figure 1), in the other 2 patients, there was no response to preoperative treatment. Patients who had curative chemoradiation had recurrent tumor on CT and PET scans.

There was no in-hospital or 30-day mortality. Early complications are listed in table 1. Three patients developed anastomotic stricture and 2 patients required bougie dilatation twice and 1 patient was dilated once. Dysphagia symptoms were relieved following dilatation. One patient developed a tracheoesophageal fistula 10 days after bougie dilatation and was successfully managed with esophageal stent placement.

Table 1: Patient characteristics and results of surgical resection

Pathologic stages of the patients are shown in table 1. In 2 of the patients extracapsular lymph node invasion was noted. In 3 patients, only 1 lymph node and in one patient, 3 lymph node metastasis were found.

The patient who eventually died of disease recurrence developed a bone metastasis 4 months postoperatively. 2 elderly patients died of non-cancer related causes, one due to major depression and cerebrovascular accident at second month and the other due to dementia, cerebrovascular accident and pulmonary complications at 8th month postoperatively.

Although, recent studies showed no superiority of these treatments to each other, fewer local recurrences and longer disease-free survival are observed in patients undergoing surgical resection[3,5,9]. Several factors are shown to influence survival following resection of esophageal tumors. Among the most important ones are: involvement of lymph nodes, more than 4 lymph nodes involved, involvement of lymph nodes distant from the primary tumor and extracapsular nodal invasion[10-12]. Lerut and his colleagues[12] in their 195 esophageal cancer patients showed that even after complete resection of esophageal tumors with extracapsular lymph node invasion 5-year survival rate was only 18%, while the 5-year survival rate was 57% in patients with no lymph node involvement.

Neoadjuvant treatment is the preferred treatment modality of clinical T3-T4 tumors with or without locoregional lymph node involvement. This treatment modality can cause regression or even tumor sterilization, and thus can increase the rate of complete surgical resection. A recent randomized study from Australia showed that while complete resection rate following neoadjuvant treatment was 80%, it was only 59% in patients who directly underwent surgery (p=0.0002)[4]. The number of involved lymph nodes was found to be less in the neoadjuvant treatment group (43 vs. 67%, p=0.003).

Complete pathologic response rate that can be achieved in esophageal cancer treated with neoadjuvant concurrent chemoradiation is nearly 25 to 30%[7-9,13]. In 5 of our 7 patients (neoadjuvant chemoradiation), a clinical response (Figure 2) was observed. 3 additional patients who completed the neoadjuvant treatment did not undergo surgical resection; due to development of lymphatic metastasis in posterior cervical chain (n=1), patient denial following a complete clinical response (n=1) and social security problems (n=1).

Fig 2: Following neoadjuvant treatment there was significant radiologic and clinical response. The histology of the tumor was squamous cell carcinoma and pathologic stage was T3N0

Re-staging following neoadjuvant treatment is also controversial. Although invasive staging with endoscopic ultrasound biopsies, videothoracoscopy and laparoscopy provide useful information, clinical applicability of these methods for the patient, surgeon and clinician is cumbersome[14]. We re-stage our patients with radiologic methods. PET and PET-CT provide useful information about the T, N and M status of the patient, however their sensitivity is lower if the size of the lymph nodes are less than 1 cm in diameter[15].

There are several factors that influence the technique of esophageal resection following neoadjuvant chemoradiotherapy. The tumors in our patients were located at the mid-lower 1/3^rd of the esophagus, thus we preferred a right thoracic approach and finalized the operation with laparotomy and left cervical anastomosis. Our choice was due to the considerations like, performing the anastomosis in a non-radiated field, performing a less morbid cervical rather than thoracic anastomosis, minimizing postoperative reflux with a high anastomosis, achieving lengthy proximal-distal margins to increase chances of complete resection and finally sampling and dissecting intrathoracic lymph nodes. We were able to achieve complete resection in all of our patients. The surgical resection following neoadjuvant treatment is usually proposed 4-8 weeks following completion of the treatment. Our data was concordant with this with an average of 7.6±1.7 weeks.

Preoperative chemoradiotherapy is believed to increase postoperative morbidity and mortality. However, in experienced centers with large patient series, morbidity and mortality rates are acceptable. Esophagectomy mortality rate following neoadjuvant treatment was 9-10% in randomized studies from France and Germany[2,3]. In series from Australia and USA, mortality rates are usually below 5%[4,6,9,16]. The high mortality rates fallowing neoadjuvant chemoradiotherapy in the European randomized studies could well be the reason for lack of any survival advantage. Treatment related complications and postoperative mortality are adversely affected in patients with poor nutritional status prior to treatment, thus instituting an enteral route (preferably a feeding jejunostomy) prior to treatment is strongly advocated[17]. In a study from Turkey, 13 patients with esophageal cancer received neoadjuvant chemotherapy. There was one treatment related mortality and 2 postoperative mortality in 8 of the patients who underwent resection. They concluded that the use of neoadjuvant chemotherapy in esophageal cancer may be harmful[18].

The use of preoperative chemoradiation in esophageal cancer is still under debate[1,19]. Long-term survival (>50% 5 year survival) can be achieved with good patient selection and appropriate surgical treatment in patients without lymph node involvement[20].

In conclusion, our limited experience shows that esophagectomy following chemoradiation can be performed in a well-selected patient group and lead to long– term survival.

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