Salvage Esophagectomy in Advanced Esophageal Cancer

Abstract

Even through the esophageal cancer has innumerable treatment options, its prognosis is still unsettled. Because esophagectomy is rarely curative, others therapies, such as chemoradiation emerging in advanced disease followed or not surgery. The salvage esophagectomy is an alternative for those patients with recurrent disease. Thus in this chapter the intend is show the results of the salvage esophagectomy in patients with esophageal cancer who had previously undergone chemoradiation and discussion about the morbidity of this surgical tecnic. Too, its show the our experience in 72 patients with unresectabeled esophageal carcinoma were treated with chemorradiation followed by salvage esophagectomy by trans-toracic approach. Patients was evaluated with regard pos-operative complications and disease free survival. The major complications was deiscence at the level of the of the anastomosis esophagogastric cervical, presents in 16 patients (22,2%) and pulmonar infection in 23 patients (31,9%). In 53 patients that were available for a five years follow-up, was a rate of 43,3% (23 patients) of disease free survival. Thus with the results its conclude that the salvage esophagectomy seems to be valuable in cases without any other therapeutic options.

1. Introduction

Esophageal malignancy is still a rather frequent condition, ranking third among the most frequent tumors of the gastrointestinal tract and the eighth most prevalent in the world [1, 2, 3, 4]. Recent studies show that esophagus neoplasms have increased by 10% per year, causing approximately 400,000 annual deaths and being the sixth leading cause of cancer death [5, 6, 7].

In Brazil, it is the seventh most common malignant neoplasm with an estimated 13,550 new cases in 2016; its highest incidence occurs in the South and Southeast regions of Brazil [8, 9].

The delay in diagnosis, excessive weight loss due to dysphagia and the association of cardiopulmonary diseases resulting from tobacco abuse make patients with a condition difficult to be controlled clinically, leaving their physicians with few therapeutic options [3, 4, 10, 11].

This reflects in the indication of esophagectomy. Although this surgical procedure remains to this day the best indication of therapy for a potential cure, because of the advanced stage of the disease found in most cases and also because of the great clinical nutritional depletion that affect patients, only 30 to 40% of them can undergo this treatment. This means that this condition has a rather unfavorable prognosis [1, 5, 11, 12, 13].

And even in patients who have clinical conditions that allow radical surgery, the prognosis is also rather poor; in fact, those patients have an average survival rate of only 15.5 months, with a two-year survival rate varying from 34 to 37% and with locoregional failure of up to 42%, as has been demonstrated in several recent studies [3, 5, 6, 10, 13, 14].

Thus, due to the low effectiveness of esophagectomy as a single treatment used with a curative purpose, for some years now new therapeutic measures have been advocated, such as radiotherapy and chemotherapy alone or associated in the pre- or post-operative period of surgical resection [5, 6, 12, 13, 15].

With the evolution of oncological therapy using more potent drug associations with fewer side effects and the advent of devices with better resolution and with more adequate techniques for performing radiotherapy, in recent years chemoradiation with exclusive intent has been suggested for a definite treatment for patients with locally advanced and unresectable esophageal cancer or patients without clinical and nutritional conditions for esophagectomy [3, 4, 6, 7, 16, 17].

However, studies with longer follow-up have shown that exclusive chemoradiation as a definitive therapy has also an unfavorable prognosis in advanced stage esophageal tumors, even if it is only with locoregional involvement without distant metastasis, with a median survival of 29 months, with local recurrence of up to 60% and a five-year survival ranging from 10 to 26% [1, 2, 4, 5, 6, 17].

Thus, the only way to attempt a potential cure in these patients with recurrence or persistence of the disease, after failure of exclusive chemoradiotherapy, would be salvage esophagectomy with a 5-year survival rate ranging from 25 to 40% [3, 4, 10, 11, 13, 16, 18].

Unlike planned esophagectomy, which is a full part of multimodal therapy for esophageal cancer, salvage esophagectomy is selectively indicated after chemoradiation failure as a definitive proposal [2, 3, 4, 6, 11, 16, 17]. In planned esophagectomy, after neoadjuvant chemoradiation, the surgical procedure is always performed, unless there is a contraindication for its performance, such as malignant disease progression or greater impairment of the patient's general condition [16, 17, 18, 19, 20].

However, the decision to perform salvage esophagectomy is often debatable, as it is often difficult to prove the persistence or recurrence of the disease. This is because, although patients may have clinical and imaging findings suggestive of malignancy, such as recurrent dysphagia and esophageal wall thickening, respectively, endoscopic biopsies are often inconclusive, due to persistent fibrosis from previous treatment.

If in the esophagectomy planned in the multimodal treatment, where the absence of tumor in the surgical specimen is considered a success, the finding of benign disease in the salvage esophagectomy can be considered a failure [2, 3, 19, 20, 21]. This is because salvage esophagectomy is another selective method of treatment in patients who still have persistent or recurrent locoregional tumors after chemoradiation failure [5, 7, 11, 21, 22]. Evidently, there are clinical situations in which the severity of the esophageal pathology justifies resection, even if it is a benign pathology, such as endoscopic intractable stenosis, ulcers and fistulas resulting from radiotherapy [3, 4, 20, 23].

Esophagectomy after chemoradiation, whether planned or salvage, can be technically difficult, since the radiation affects the mediastinum structures, either earlier, due to the presence of an inflammatory process, or later, due to the evolution to fibrosis [3, 12, 13, 22].

The greater tissue injury is caused by the highest irradiation dose, whether total or fractional, the greater extension of the irradiation field, and this may influence the greater morbidity of salvage esophagectomy [1, 4, 11, 19, 20, 21]. Some series have shown that tissue damage is greater in patients undergoing this type of resection, since the total dose used in chemoradiation with final intention is generally higher, and on average 50 to 60 Gy, for 30 to 40 Gy for the group of patients initially submitted to neoadjuvant therapy [12, 14, 24, 25, 26].

Another relevant fact is that in planned esophagectomy the time interval between the end of chemoradiation and the surgery is shorter (20 to 30 days), which means that there is still only an inflammatory process at the mediastinal level, whereas in salvage esophagectomy, because the interval for surgery is longer, on average, from 3 to 6 months, severe fibrosis develops, with increasing difficulty to dissect the esophagus with the mediastinal structures predisposing to a greater potential for morbidity [1, 15, 18, 22].

This fact, associated with skepticism regarding the cure for esophageal cancer, explains the reluctance of many surgeons to perform this type of procedure, because despite this therapeutic modality being more popular in recent years, some series have not yet demonstrated adequate standardization. This may hinder the results of the actual validity of salvage esophagectomy after previous chemoradiation with exclusive intent [15, 27, 28, 29].

In recent years, with the improved evolution and standardization of the surgical techniques, better assessment of postoperative complications, better standardization of staging by the latest TNM consensus [30], with a more adequate selection of patients with study variables that can be standardized in the same way, caused several series to begin showing better results with the use of salvage esophagectomy [3, 4, 6, 11, 13, 17, 19, 25].

2. Surgical procedure

2.1 Patients selection

A careful selection of patients is required, since in most cases they present with pulmonary involvement, as they have chronic obstructive pulmonary disease, in addition to the nutritional deficit worsened by previous chemoradiation.

Hence the importance of an adequate preoperative clinical evaluation with pulmonary function tests in which the expiratory volume of the first second (FEV1) and the pulmonary diffusing capacity (DLCO) are 50% greater than expected [18, 21].

Also in order to have a more adequate selection of patients, it would be desirable that they were non – smokers or having quit smoking at least 3 months prior to the surgery, and also underwent chest physiotherapy at least 30 days prior to the surgery [21, 31].

Regarding nutrition, it is important that patients perform a well-appropriate preoperative nutritional assessment, since most of these patients have marked nutritional deficits resulting not only from the chemotherapeutic treatment but also from the disease that may still be present or relapse. Thus, in recent years, some important indicators have been advocated for the assessment of the nutritional status:

1. Nutritional Risk Screening 2002 (NRS 20020): it is a nutritional screening instrument for determining nutritional risk, taking into account weight loss, reduced food consumption, body mass index and disease severity [32].

2. Subjective Global Assessment (SGA): is an instrument that subjectively assesses the nutritional status of the sick individual, based on scores given to weight loss, food consumption and clinical and physical signs of malnutrition [33].

3. Anthropometry indicators: the most common indicators are body weight, body mass index (BMI), arm circumference (AC), triceps skinfold (tsf), arm muscle circumference (AMC) and calf circumference (CC) [32, 33, 34].

4. Laboratory tests: tests associated with nutritional status, such as albumin, pre-albumin, transferrin and lymphocyte count.

After this evaluation, if it is confirmed that the patients are malnourished, parenteral or enteral nutrition is indicated during a variable time of 15 to 30 days in the preoperative period, depending on the degree of malnutrition.

2.2 Anesthetic act

Due to the fibrosis that occurs at the thoracic level, upon previous chemoradiation, it is recommended that the thoracic route be used, either by thoracotomy or videothoracoscopy to have easier access to the esophagus [3, 4, 35, 36, 37].

Thus, it is necessary to perform anesthesia with single-lung ventilation with a minimum fraction of inspired oxygen, to prevent further damage to the lung parenchyma, which is often already compromised by actinic action [11, 18, 31].

2.3 Surgical technique

2.3.1 Resection

Despite the main objective of the surgery being the performance of a complete resection (R0), especially when this procedure is the primary treatment of cancer; this same strategy has to be applied carefully after chemoradiation. Thus, the salvage esophagectomy series indicate, in most cases, a resection of the entire thoracic esophagus until reaching the cervicothoracic transition, through direct vision, by right thoracotomy, to facilitate the dissection of the organ due to the presence of fibrosis that ensued previous radiotherapy and, therefore, minimizing complications [2, 4, 12, 13, 17, 20, 29].

In recent years with the advent of minimally invasive surgery, demonstrating the advantages of minor trauma, some series have proposed this access route. Ishiyama et al. [35], in a recent study, comparing salvage esophagectomy by videothoracoscopy in 20 patients against 62 patients submitted to this procedure using right thoracotomy, showed that there was a significantly lower incidence of pneumonia in the video group (20.0%) compared to the open surgery group (48.3%). According to these authors, this result is due to the fact that the prone position used in videothoracoscopy improves oxygenation when compared with thoracotomy, and artificial pneumothorax where the gravity condition when accessing the operative field induces less lung compression when compared with the right lateral decubitus position, thus resulting in less damage to the lung tissues, with concomitant reduction in atelectasis with preservation of oxygenation and, potentially, preventing postoperative pneumonia. This fact has also been demonstrated by other authors [36, 37, 38].

Recently, high-definition video systems for laparoscopic and thoracoscopic surgery have shown advantages over conventional open surgery, as they provide sharper images of the anatomical structure, which can often be quite distorted by previous radiotherapy [35, 38, 39]. Thus, the recognition of microanatomy is better recognized, with better preservation of nerves and vessels when compared to open surgery, thus being able to reduce blood loss [36, 37]. In addition this preservation of vessels is also important, especially in relation to the trachea wall, which is supplied by a network of vessels along its longitudinal face, and thus, with a better visualization of this anatomy, it is possible to prevent this organ ischemia with reduction of pneumonia and postoperative tracheal fistula [35, 39].

Regarding lymphadenectomy, there is no well-defined consensus, since some authors suggest routine lymph node dissection in II and III surgical fields and other authors only in lymph node stations with suspected metastases, to avoid devascularization of the airways [11, 19, 20, 29, 31, 35, 40].

Although there is controversy regarding the increase in overall survival, some authors have recently suggested salvage lymphadenectomy, that is, only lymphadenectomy, without esophageal resection, because the disease is only located in the locoregional lymph nodes, after chemoradiation with definitive intent, as it is less invasive and has a low incidence of complications [13, 41, 42]. Katoe et al. [41] demonstrated in 30 patients submitted to salvage lymphadenectomy that the overall survival was significantly higher when there was recurrence of the disease in the lymph nodes in relation to the residual disease in the same lymph nodes, being 21.7% to 0.0%, respectively; they also showed that overall survival was significantly higher when lymphadenectomy was performed outside the irradiation field, with 47.6% to 8.9%, of the patients, respectively.

Some authors have also advocated partial parietal pleurectomy during salvage esophagectomy, in order to promote a pleural symphysis and provide a more conservative conduct in the event of a potential lymphatic fistula [3, 29, 43].

2.3.2 Esophageal reconstruction

Esophageal reconstruction, unlike the esophagectomy resection time, is responsible for most septic and pulmonary complications after surgery, which makes some authors recommend that it be performed in a second surgical procedure, especially in more nutritionally undermined patients and when the viscera to be transposed already presents a jeopardized perfusion [5, 27, 29, 43, 44, 45]. Although the organ to be transposed in the reconstruction may present a good perfusion in the abdomen, perfusion can be hindered by the anatomical distortion of the immediate transposition [14, 29, 43, 44].

Thus, some surgeons have supported reconstruction by gastric transposition to the cervical region 4 to 6 weeks after resection, although more recently other surgeons indicate their preference for a prompt reconstruction [2, 3, 5, 11, 13, 17, 29, 44, 45].

Although it is already well standardized that the reconstruction route is carried out through the posterior mediastinum because it is more anatomical and physiological, some authors still believe that the anterior mediastinal route is more favorable, as it minimizes the consequences of a probable anastomotic fistula at the cervical level besides being more easily diagnosed and managed. Most of the time drainage of the cervical region at bedside will do [3, 6, 7, 12, 18, 29, 44, 45].

A variant that has been proposed, although with little acceptance, in the framework of gastric transposition through the anterior mediastinal route is not performing an immediate esophagogastric anastomosis, with the advantage of minimizing the anastomotic fistula and aspiration of gastric contents into the airways [11, 23, 39, 43]. In addition, this access route has the advantage of avoiding tracheobronchial compression and preventing a fistula of the organ transposed with the airways.

3. Post-operative complications

With the evolution of chemoradiation, with greater potential as a definitive treatment for esophageal cancer, many series began to indicate salvage esophagectomy more frequently, especially in patients with recurrent tumors and with a stage less than or equal to T2 after oncological treatment [1, 2, 4, 11, 13, 14, 16, 20, 21].

Thus, it is important to remember the complications that this type of resection can cause, with a frequency of up to two or three times greater than that of esophagectomy without previous treatment [13, 15, 22, 29, 31]. Recently Mitchell et al. [18], comparing the postoperative morbidity of 35 patients undergoing salvage esophagectomy with 41 patients undergoing planned esophagectomy, showed complications with higher morbidity of 71.4% and 36.6%, respectively; and in the same comparison, mortality at 90 days after surgery was 17.1% and 9.8%, respectively.

Thus, the postoperative period of salvage esophagectomy is notable for several complications, especially those described below:

3.1 Respiratory failure

Although this complication does not fit a precise classification, adult respiratory distress syndrome and pneumonia are the two most frequent conditions [18, 21, 29, 46]. Chemoradiation, even without surgery, can already cause the respiratory distress syndrome and, associated with the surgical trauma of esophagectomy, predisposes more intensely to this syndrome [7, 12, 14].

Actinic pneumonia resulting from irradiation is probably the first injury to the lungs, and the release of cytokines during the surgical procedure would increase the intensity of the lung parenchyma injury [3, 18, 29, 46].

Mechanical ventilation during surgery or in the immediate postoperative period can also initiate an inflammatory cascade in the lungs, especially when there is a need for prolonged periods and single-lung ventilation with a high volume of the fraction of inspired oxygen, in addition to the perfusion in only one lung [46].

Lymphatic obstruction resulting from irradiation or surgical excision, for those authors who advocate mediastinal lymph node drainage, may also contribute to acute lung injury [19, 47].

Another well-known etiology, which can exacerbate the inflammatory cascade characteristic of adult respiratory distress syndrome, would be tissue ischemia with the stomach transposed for transit reconstruction, even if this is not sufficient to cause gastric necrosis [21, 23, 29].

Pneumonia after salvage esophagectomy has also many causes, such as chronic obstructive pulmonary disease, resulting from long-term smoking, present in most of these patients, is the most relevant factor, as has been demonstrated in several series [11, 13, 15, 20, 23, 27, 28, 29]. And this complication is also significantly lower in planned esophagectomy when compared to salvage esophagectomy, due to the lower intensity of irradiation in patients who undergo this type of surgical tactic after neoadjuvant chemoradiation [18, 21]. This was well demonstrated by Mitchell et al. [18] who, comparing 41 patients undergoing neoadjuvant therapy and planned esophagectomy with 35 patients undergoing salvage resection after chemoradiation with exclusive intent for having in the initial stage T4b presented an incidence of pneumonia from 12.2% to 34.3%, respectively. Hence it is important to perform a good preoperative preparation with adequate respiratory physiotherapy.

Also the great importance of the advent of video thoracoscopic surgery that offers the access route used for esophageal resection, potentially reduces the damage to lung tissue with reduced atelectasis and greater oxygenation and, consequently, a lower incidence of pulmonary infection, as has been recently demonstrated in some series [35, 37, 38].

The deficient nutritional status, characteristic in most patients with esophageal cancer, can be further exacerbated by previous chemoradiation which, associated with immunosuppression also present in those patients, can more often predispose to pneumonia. Hence it is important to perform an assessment and provide an adequate preoperative nutritional support, to try to minimize this complication.

Another fact that can also predispose to pulmonary infection is the edema of the cervical region resulting from the dissection of the esophagus which occurs in the first postoperative days and can hamper swallowing in a transient way and thus predispose to aspiration of secretions from the mouth cavity and pharynx into the tracheobronchial tree [29].

The introduction of a nasogastric tube to decompress the stomach in the immediate postoperative period also favors the release of the upper and lower esophageal sphincters and thus may cause reflux into the airways, with consequent pulmonary injury [29, 32].

3.2 Esophago-visceral anastomosis dehiscence

The etiology of esophagogastric anastomosis dehiscence is multifactorial, but technical errors and insufficient tissue perfusion of the gastric wall are the most important causes [31, 43]. Vascularization of the transposed stomach for esophageal reconstruction is performed by the right gastroepiploic and right gastric vessels, since the left gastric, left gastroepiploic and short vessels are sectioned. Thus the gastric duct survives because the stomach has a rich submucosal vascular plexus. Previous irradiation, especially with a dose > or equal to 50 Gy, can hamper the microcirculation of the gastric conduit, with consequent areas of necrosis and providing anastomotic dehiscence [21, 22, 29]. This was very evident in the review carried out by Jamel & Markar [21] who, in the evaluation of 11 studies with 1906 patients with esophageal cancer, showed that the group of patients undergoing salvage esophagectomy had significantly 21.8% anastomotic dehiscence for 8.1% of this complication for the group of patients undergoing planned esophagectomy. And this fact is also demonstrated by other authors [18, 28, 29, 31].

With the advent of mechanical sutures to perform anastomoses of the digestive tract, whether in benign or malignant conditions, perhaps this complication could be minimized in patients undergoing salvage esophagectomy. This is because this suture provides a better coaptation of the anastomotic stumps as it is double and inverted [48, 49].

The morbidity of esophageal-gastric anastomosis dehiscence depends on the location, whether cervical or thoracic, on the viability of the gastric conduit and on the conditions of the perianastomotic tissues, to try to block the fistula resulting from the dehiscence. The most favorable situation is when dehiscence occurs in the cervical region with a viable gastric conduit and protected by the soft tissues around the anastomosis.

The management for the treatment of this complication is based on the severity of the dehiscence. If severe, early and in the thoracic region and with hemodynamic undermining, aggressive surgical intervention is mandatory; however, if this complication occurs later, usually after the fifth postoperative day and in the cervical region, the conduct may be more conservative, with drainage of the cervical region at the bedside [43, 45, 48, 49]. However, conservative management of this complication after salvage esophagectomy can often be unsuccessful if the tissue bed at the level of the anastomosis has been irradiated [18, 21, 29].

3.3 Recurrent laryngeal nerve injury

Recurrent laryngeal nerve injury can occur in any esophagectomy technique, but this complication is more common after salvage esophagectomy due to mediastinal fibrosis resulting from irradiation, which causes intense adhesions of this nerve to the esophagus and to the mediastinal lymph nodes, making dissection difficult [3, 5, 10, 11, 22, 31].

As a consequence, this lesion causes vocal cord paralysis, a complication that is poorly tolerated by patients undergoing salvage esophagectomy, as it promotes pulmonary aspiration more frequently, limits the patient's ability to cough and thus worsens already existing lung lesions due to actinic action.

3.4 Airway necrosis

Extensive necrosis of the trachea is a rare but usually fatal complication after salvage esophagectomy [19, 29, 43]. On the other hand, focal necrosis of the airways is more common, with a rate of up to 23%, in most series that demonstrate this type of complication [4, 24, 43, 50].

And this complication may occur due to mediastinal fibrosis resulting from previous more intense irradiation, which predisposes to inadvertent injuries to the airways during the surgical procedure that, associated with vascular damage resulting from actinic obliterating endarteritis can induce airway necrosis. This complication has caused some authors to avoid the large dissections of three-field esophagectomy, as this procedure is more indicated in esophagectomy without previous chemoradition to minimize those complications [12, 15, 17, 18, 19, 24].

This complication, once present, is evidenced by a fistula in the mediastinum and/or pleura, progressing to pneumomediastinum or pneumothorax.

Conservative treatment of these fistulas is controversial, since, due to previous irradiation, the tissue injury at the mediastinal level becomes difficult to be blocked. And this treatment becomes even more difficult when the necrotic segment of the tracheobronchial tree develops a fistula into the stomach transposed to the posterior mediastinum, since, besides having difficulty in ventilation, a continuous aspiration of gastric secretion into the lungs occurs [29, 43, 50]. Although treatment with a self-expanding prosthesis is a valid option, it can, though, worsen the airway ischemia [43].

3.5 Chylothorax

This is a complication that, although quite uncommon, can also occur due to the difficulty in identifying the thoracic duct during esophageal dissection, resulting from intense mediastinal fibrosis caused by previous irradiation [29, 31]. Mitchell et al. [18], comparing the incidence of this complication among patients undergoing planned and salvage esophagectomy, showed that this complication was null for 11.4% in both cases. Lymphatic fistulas with high output, generally exceeding 1 liter per day, has early surgical indication, with thoracic duct ligation [18, 29]. On the other hand, with low-output fistulas, the conduct may be conservative, associating parenteral nutrition, chest drainage, and chemical pleurodesis [18, 29, 31].

4. Post-surgical care

Sepsis is the leading cause of mortality after salvage esophagectomy. It often starts with pulmonary involvement and ends with multiple-organ failure.

Thus, to prevent this morbid sequence, the surgical team must detect septic complications as early as possible and initiate aggressive treatment. Time is often lost in the evolution of the patient's septic condition when it is thought that the infection is a consequence of pulmonary atelectasis or urinary tract infection. Gastric necrosis and anastomotic dehiscence, especially if it occurs up to the third postoperative day as well as pleural empyema and intraperitoneal abscess are important septic complications to consider [18, 22, 23, 28, 46].

Hence the importance of performing upper digestive endoscopy as early as possible when gastric necrosis is suspected, which, if confirmed, has an immediate indication for a new surgery with resection of the interposed stomach [18, 29]. If there is clinical evidence of a fistula with secretion drainage through the incision in the cervical region and without hemodynamic repercussions, drainage of this region should be performed through cervicotomy at bedside [23, 29, 43, 45].

Patients undergoing salvage resection, because their general condition is more undermined, require the most adequate nutritional support. Thus, in addition to an adequate intermittent nutritional assessment in the postoperative period, it is also of fundamental importance to carry out a careful investigation of short- and long-term food intake after esophageal resections. This is because the changes that may occur in the process of nutrient absorption as a result of the surgical procedure performed, cause many patients, even six months after surgery, to be unable to meet their energy, protein and micronutrient requirements [51, 52, 53].

Hence, some researchers suggest the supplementation of the oral diet with an enteral diet, even in the postoperative period, in the medium term after esophageal resection [51, 54, 55].

5. Survival

More recently, some series have shown that the results, in terms of medium and long-term survival after salvage esophagectomy, are better in patients with residual or recurrent tumor classified as T2 or less after chemoradiation with previously definitive intent and also R0 resection [6, 7, 11, 13, 17, 21, 56].

This was well demonstrated in the study by Okamura et al. [17] who, evaluating 35 patients who underwent salvage esophagectomy after chemoradiation with exclusive intent, had 2 and 5-year survival rates with T2 tumors, of 85% and 65%, respectively; 20% and 0% survival, respectively with tumors greater than or equal to T3; and the same in relation to resection, since at 2 and 5 years there was 50% and 33% survival with R0 resection and 15% and 0% with resection R1/R2.

Fujita et al. [57] also demonstrated in a prospective, non-randomized study, in 53 patients, the need for esophagectomy after exclusive radical chemoradiation. In patients who did not fully respond to chemoradiation, surgical resection increased survival from 3 to 5 years, with a rate of 38% and 27%, respectively, and in most of these patients with T2 tumors the resection was R0.

Hence, it is important to proceed with an adequate patients’ selection in the preoperative period, using well-suited imaging exams to assess the tumor extension. Of course, this can be difficult, because of the anatomical changes that occur due to the previous treatment that causes thickening of the esophageal wall.

Okamura et al. [17], evaluating this variable, demonstrated in their series that there was an accuracy of 91.4% with the use of high-resolution chest tomography between the pre and postoperative periods, in relation to the thickness of the tumor. However they suggest that, if there is any doubt about this information, PET-CT and echoendoscopy are indicated.

More recently, it has been demonstrated that the complications that may occur in the immediate postoperative period could have an impact on the survival of patients, due to the deterioration of the general and nutritional status causing an immunity deficit [11, 31]. In addition, postoperative complications can cause prolonged inflammation and produce inflammatory cytokines, which can induce tumor cell proliferation [11, 58].

This was clearly evidenced in the study by Sugimura et al. [31] who, assessing 73 patients who underwent salvage esophagectomy, showed that the 3- and 5-year overall survival of patients with some postoperative complication was 29.4% and 29.4% respectively, compared with 59.9% and 54.9%, respectively, among patients without any postoperative complications.

It is thus important to proceed with a good preoperative evaluation and careful monitoring in the intra and postoperative period to try to minimize this morbidity.

It has been shown that low albumin level, high C-reactive protein level, low body mass index, excessive intraoperative blood loss, poor nutritional status, advanced stage tumors and clinically positive lymph nodes and greater or equal irradiation at 60Gy, are variables associated with a higher occurrence of postoperative complications [11, 31].

6. Experience of the thoracic surgery service of hospital PUC-Campinas Brazil

From January 1995 to December 2021, 573 patients underwent esophagectomy for esophageal squamous cell carcinoma. Out of these, 72 underwent salvage esophagectomy for residual or recurrent disease after previous chemoradiation with exclusive intent and having an initial stage T4b.

At restagement for indication of salvage surgery, 59 patients (81.9%) had T2 or smaller tumors, and 13 (18.1%) T3/T4a.

All patients underwent esophageal resection by right thoracotomy and reconstruction of the digestive tract with gastric transposition to the cervical region in the first or second surgical procedure.

In the early postoperative evaluation regarding complications, 16 patients (22.2%) presented with cervical esophagogastric anastomosis dehiscence with good evolution fistula with conservative treatment in 15 patients; 3 patients (4.1%) had chylous fistula, and surgical treatment was indicated in 2 of them, with good evolution; 9 patients (12.5%) had recurrent laryngeal nerve paralysis, being definitive in 2 of them; 23 patients (31.9%) had pneumonia with good evolution, with specific treatment in 19 of them; 2 patients (2.7%) had a fatal cardiovascular event due to probable pulmonary thromboembolism.

Seven patients (9.7%) died due to complications in the first 30 days after surgery.

In the late evaluation, it was possible to follow up 53 patients for disease-free survival assessment: at 1 year – 51 patients (96.2%); at 3 years – 26 patients (49.0%) and at 5 years −23 (43.3%) patients. All patients who survived up to 5 years had T2 stage tumor or lower and underwent R0 resection.

7. Final considerations

Exclusive chemoradiotherapy in esophageal cancer has become quite popular in recent years, especially in cases with advanced locoregional disease and in those patients without physiological reserve for esophagectomy. With the evolution of nutritional support that was developed more recently, many patients were able to recover their general conditions, becoming fit for surgical resection.

In recent years, several series have demonstrated that salvage esophagectomy is technically feasible, despite the high morbidity, especially with regard to septic complications and adult respiratory distress syndrome. As these postoperative complications can infer a worse prognosis in the survival of these patients, it is important to prevent these complications and to keep these patients monitored for a long time in the postoperative period, especially with regard to nutritional status.

And this is important, because salvage esophagectomy is the only cure for cases of recurrence or persistence of the disease after exclusive chemoradiation. It therefore represents the best second-line treatment for local failure after exclusive chemoradiation, although further studies are needed to assess whether persistent disease has a worse prognosis than the recurrent disease after esophageal resection.

Acknowledgments

To Hospital Puc-Campinas.

Conflict of interest

The authors declare no conflict of interest.