Topical issues of esophageal cancer and gastroesophageal cancer surgery

© Красносельський М. В., Старіков В. І., Ходак А. С., 2020 РЕЗЮМЕ Актуальність. Рак стравоходу (РС) займає 14-те місце у структурі онкологічної захворюваності населення України. Гастроезофагеальний рак (ГЕР) зустрічається в кілька разів частіше, вважається, що ГЕР становить понад 20 % від усіх раків шлунка. Результати лікування раку цієї локалізації є найгіршими серед інших онкологічних захворювань. Це пов’язано з високою задавненістю захворювання, виявленого вперше, високою післяопераційною летальністю (15 %) та низькою п’ятирічною виживаністю хворих. Мета роботи. Проаналізувати літературні джерела, які стосуються розвитку хірургії раку стравоходу та гастроезофагеального раку в хронологічному аспекті, та визначити основні напрямки подальшого розвитку хірургічного лікування цієї патології. Матеріали та методи. Огляд літератури охопив доступні повнотекстові публікації, які були отримані внаслідок літературного пошуку у вітчизняних і закордонних базах даних. Пошук був обмежений дослідженнями, опублікованими в період 1975–2020 рр. Особлива увага приділялась аналізу ефективності виконання лімфодисекції та методикам формування стравохідно-шлункового анастомозу в порівняльному аспекті. У роботі також проаналізовані матеріали власних багаторічних досліджень авторів з цієї проблеми. У ДУ «ІМР НАМН України» та обласному клінічному онкологічному диспансері з 1990 до 2018 року було проліковано 250 хворих на рак стравоходу та гастроезофагеальний рак. Результати та їх обговорення. Дані літератури свідчать про те, що неспроможність стравохідно-шлункового анастомозу займає друге місце серед ускладнень. На перше місце виходять серцево-судинні та легеневі ускладнення. При виконанні трьохзональної лімфодисекції п’ятирічна виживаність збільшується на 10 %. Неспроможність стравохідно-шлункового анастомозу в провідних клініках складає від 3 до 9 %. Виконання пластичного стравохідно-шлункового анастомозу підвищує його фізіологічні властивості. Актуальні питання хірургії раку стравоходу і гастроезофагеального раку Красносельський М. В.1, ORCID: 0000-0001-5329-5533, e-mail: medrad20@ukr.net Старіков В. І.2, ORCID: 0000-0001-9577-8760, e-mail: star.onco@i.ua Ходак А. С.2, ORCID: 0000-0001-6791-9757, e-mail: a.khodak@i.ua 1 Державна установа «Інститут медичної радіології та онкології ім. С. П. Григор’єва Національної академії медичних наук України», Харків, Україна 2 Харківський національний медичний університет, Харків, Україна


INTRODUCTION
Esophageal cancer (EC) ranks 14th in the structure of cancer incidence in Ukraine [1]. Gastroesophageal cancer (GEC) is several times more common. It is estimated that cancer in this area accounts for more than 20 % of all gastric cancers [2]. According to the National Cancer Institute, in 2008 there were 16,470 new cases of ES in the United States, of which 14,280 died from the disease [3].
The leading clinical symptom of EC and GEC is dysphagia, which tends to progress, and in the final stage of the disease there is complete dysphagia, dystrophy and painful death in the result of starvation. The disease has a latent course for a long time, and with the appearance of the first episodes of dysphagia, as a rule, the tumor has already affected 2/3 of the esophagus circumference.
The anatomical location of the esophagus, its proximity to the heart, aorta, trachea, bronchi, vagus nerves and others makes the problem complex moreover the location in the three anatomical zones determines the features of esophageal tumors lymphogenic metastasis.
Till now the complete cure for EC and GEC can be achieved only by surgery. The five-year survival of patients is from 25 to 35 % according to various authors [4]. At the same time, postoperative mortality in EC and GES is up to 15 %, and only in leading clinics it is 3-9 % [5,6]. Objective statistics of postoperative complications and mortality are aggravated by the fact that in some clinics EC operations are episodic, as there is no personal experience of the surgeon in performing such operations, there is no experience of medical staff, and this negatively affects the immediate and long-term treatment results. The majority of operated patients (from 50 to 60 %) die within the first 2 years due to local recurrence of the disease, which is to some extent due to insufficient radicalism of the operation [7,8].
EC and GEC surgery is one of the most complex and relatively young sections of oncosurgery. Quite a few clinics in the world have extensive experience in the surgical treatment of cancer in such locations, so there are many debatable issues, the solution of which is influenced by different, sometimes diametrically opposed, views.
Purpose. To analyze the literature sources related to esophageal cancer and gastroesophageal cancer surgery development in chronological terms and to define the main directions for further development of surgery of this pathology.

MATERIAL AND METHODS
The literature review has involved available fulltext contributions obtained via literature search in domestic and foreign databases. The search was restricted to the studies published within the 1975-2020 timeframe.
Special emphasis was placed on the effectiveness analysis of lymph node dissection and methods of esophagogastric anastomosis forming, in a comparative aspect. The paper also analyzes the materials of the authors' own long-term studies related to this issue. From 1990 to 2018, 250 patients with esophageal cancer and gastroesophageal cancer were treated at SO «IMR of the NAMS of Ukraine» and the regional clinical oncology dispensary.

RESULTS AND DISCUSSION
The expediency and oncological adequacy of the various approaches used for esophageal resection is still the subject of heated debate among surgeons and namely between surgeons and oncologists until now. In particular, with regard to transthoracic and transhiatal access, there are different, mostly polar views that have divided representatives of different surgical schools.
F. Torek successfully performed the first transthoracic resection of the esophagus through the left thoractomy access in 1913. There was no recovery stage, the operation ended with cervical esophagostomy and gastrostomy. The same year, the Austrian surgeon W. Denk developed the technique of transhiatal esophagectomy without thoracotomy with abdominal and cervical access with the formation of an anastomosis on the neck, as an option for gentle surgery with less surgical trauma. This operation was introduced into the clinic thanks to the work of G. Turner in 1930. At that time, the emergence of such a method of operation was natural, because in the absence of adequate analgesia and lungs ventilation during surgery, thoracotomy itself was a great threat to the patient's life.
In 1929 Tohru Ohsawa from Kyoto University was the first to perform performed esophageal resection and gastrectomy with a one-stage esophageal-small intestinal anastomosis through the left thoracolparotomy access.
In 1946, the Englishman I. Lewis presented to the Royal Society of Surgeons his method of resection of the esophagus in midthoracic cancer. After midline laparotomy, gastric mobilization, the author performed a thoracotomy on the right, performed esophagus resection and formed an esophagogastroanastomosis.
One of the main ideologues of the widespread introduction of abdominocervical surgery for esophageal cancer is M. Orringer from the Michigan Ann Arbor Cancer Clinic, who «rediscovered» this operation in 1978.
Вивчення протоколів розтину померлих після екстирпації або резекції стравоходу з приводу раку over the bifurcation of the trachea; sometimes there are pronounced heart rhythm disorders. Despite the fact that this technique does not perform a thoracotomy, there are often pulmonary complications in the postoperative period. Failure of the esophagogastric anastomosis in the neck is up to 15 %.
According to D. Skinner (1983), the experience of transhiatal operations is interesting only in terms of historical excursion into the «dark years» of surgery. Features of access, which allow to mobilize the esophagus only «blindly», affect the long-term results of treatment [9].
In 1995, L. Bonavina published the results of surgical treatment of squamous cell EC at stage T1NoMx, and found that in patients with invasion of the submucosal tumor 5-year survival in transthoracic access was 54.2 %, and in transhiatal -25.5 %. Other authors also point to the positive effect of transthoracic access on 5-year survival in EC [10]. Some of them believe that transhiatal resection (TR) of the esophagus creates the preconditions for the development of residual (abandoned) tumors, which leads to local recurrence in the mediastinum in 60-79 % of patients [11,12].
It was stated at the ISDE conciliation conference (1995) that ETHR is preferred mainly by general surgeons, and transthoracic resection by oncology surgeons.
Left thoracoabdominal access is adequate only in GEC, it allows you to mobilize the esophagus to the aortic arch and leave the margin up from the visible edge of the tumor by 5-8 cm from this access it is also possible to remove bifurcation, middle and lower paraesophageal, diaphragmatic and posterior mediastinal groups of lymph nodes (LN).
Thus, in esophageal cancer, a combined (laparotomy) approach is considered optimal, which allows to mobilize the tumor visually in compliance with the rule of radicalism, perform adequate mediastinal lymph node dissection and to form an esophagogastric anastomosis in good conditions.
Significant development of intraorgan and extraorgan lymphatic system, with the predominance of «longitudinal» vector of lymph outflow over transverse, causes peculiar features of lymphogenic metastasis in EC in the form of significant directional variability, lack of segmentation, the appearance of intramural (intramural) metastases in the esophagus, sometimes 8-10 cm from tumor, the appearance of «jumping» metastases in 30 % of cases. EC is characterized by massive metastasis to the cervical, mediastinal and abdominal lymph nodes. Recurrence occurs in 25-60 % of cases after conventional EC operations [13].
The study of autopsy protocols of the deceased after extirpation or esophagus resection for cancer showed that unremoved metastases in the mediastinum LN occur in every 4th patient [14]. In this regard, there is a need to standardize the method of preventive lymph dissection of regional metastasis areas, which has both therapeutic and diagnostic nature.
surgeon H. Ide et al. [14] from the Tokyo Institute of Gastroenterology in 1998: • standard 2-zone (abdominal and mediastinal (to the level of bifurcation of the trachea) -2S); • extended 2-zone (abdominal and bilateral mediastinal lymph dissection to the level of the upper aperture) -2F (from English field -field); • 3-zone (abdominal, bilateral mediastinal and cervical lymph dissection) -3F.
At the conciliation conference of the International Association of Esophageal Diseases (ISDE), held in 1994 in Munich, the classification of lymph dissection in esophageal cancer was proposed by R. Bumm et al. [15]: The areas of lymph dissection are presented schematically in Fig.1.
The development and implementation of operations with 3-zone lymph dissection in EC began Japanese surgeons in 1970 (Y. Sannohe et al.). According to their data, 4-year survival after 3-zone lymph dissection was 41.3 versus 21.4 % after operations with 2-zone lymph dissection [16]. The introduction of 3-zone lymph dissection contributed to an increase in 5-year survival by 10 % [17,18].
According to numerous authors, an average of 20-25 LN is removed with standard operations, 40-50 -with extended operations, 70-75 -with 3-zone. It was also shown that with LN lesion along the recurrent nerve, the 5-year survival at 3F lymph dissection was 27.9 versus 0 % at 2 F [19].
One of the frequent complications of 3-zone surgery is paresis of the vocal cords from 5 to 70 %, as well as ischemic damage to the trachea.
Today, surgical treatment of patients with cancer of the thoracic esophagus without lymph dissection is not considered in principle as an acceptable option for surgical treatment.
anastomosis. This is due to the high frequency of anastomosis failure from 6 to 15 %, often leading to a fatal outcome [5,20].
The technique of esophagoplasty must meet two main requirements -safety and functionality. The latter one provides for the maximum restoration of the normal esophagus functions: food transport, antireflux and antiaspiration properties, providing antistenotic.
The choice of esophageal plastics method depends on several circumstances: the nature of the disease, the level of damage, the individual characteristics of the patient, the traditions of the clinic and the surgeon personal experience. The last two factors are of major importance.
M. Hirsch in 1911 and Jianu in 1912 were the first who proposed to form an artificial esophagus from the large curvature of the stomach and place it in the subcutaneous canal prethtoracically.
J. Garlock (1946), R. Sweet (1948), E.L. Bereziv (1951) developed a wide gastric stem plastic with an anastomosis in the left pleural cavity in cancer of the middle and lower third of the esophagus. Currently, a onestep resection of the esophagus from primary esophagoplasty with a wide gastric stem has been recognized by surgeons.
During resection of the esophagus, the latter is connected with the stomach in the dome of the pleural cavity. However, many surgeons are known to form connections at the neck at any level of esophageal damage to prevent such dangerous complications as failure of the intrapleural esophageal anastomosis and pleural empyema.
However, numerous studies have shown the advantage of intrathoracic anastomoses over cervical ones in terms of functionality. Paresis of the recurrent nerve, incoordination of swallowing and aspiration happen more often in cervical anastomoses than in intrapleural ones (29.5 and 13.4 %, respectively). Typical complications for cervical esophageal-gastric anastomoses are failure of sutures and stenosis of the anastomosis. The incidence of cervical anastomosis failure, according to various data, ranges from 6 to 40 %, averaging 15-20 % [20,21].
Quite often (according to various data, from 22 to 50 %) the cervical anastomosis, which initially healed, is complicated by stenosis, which in most cases requires endoscopic dilatation [22].
The formation of the esophagogastric anastomosis is performed manually or with the help of staplers. The use of the latter ones reduces the time of surgery, but often leads to unpleasant complications of gastropharyngeal reflux and anastomotic stenosis. Besides the hardware suture worsens the conditions of tissue regeneration and does not allow to perform a number of techniques aimed at improving the functional qualities of the remaining stump of the stomach.
To increase the reliability of the anastomosis imposed with the use of the device, a number of original techniques have been proposed, which provide for separate suturing of the mucous and submucosal layers by the device, and muscle manually [23]. However, in oncology clinics, a deep esophageal-gastric anastomosis, which has high reliability and functional properties, is mostly preferred.
Іншим поширеним методом пластики стравоходу шлунком є пластика ізоперистальтичним шлунковим We have proposed an anastomosis, with the formation between the esophagus and the bottom of the stomach, which is anatomically supplied with blood worse than other parts of the stomach, but most adapted to ischemia. The formation of an anastomosis in the area of the bottom of the stomach allows you to perform a plastic technique, which results in the formation of an elastic cuff around the latter and a new gas bubble. The peculiarity of our modification of this anastomosis is the imposition of one row of sutures on the anterior wall (Fig. 2). This makes the newly formed bottom of the stomach more mobile [24].
The whole period of anastomosis formation requires great care in relation to the esophagus. We do not allow the capture of the distal part of the esophagus with a L-shaped clamp. To improve the technical conditions of the operation, it is possible to capture only the mucous and submucosal layers of the esophagus, followed by cutting off this area after applying the first row of sutures to the posterior lip of the anastomosis. Then a circularly removed area of the mucosa is examined for the presence of tumor elements in it.
Another common method of gastric esophageal plastics is isoperistaltic gastric stem plastics with great curvature. The creation of an isoperistaltic stem with a large curvature allows to lengthen the graft by 8.9 ± 2.5 cm. However, a meta-analysis showed that esophageal plastic with a narrow isoperistaltic stem of the stomach is a nonfunctional operation. If such plastic is used, the frequency of fistulas of the esophageal-gastric anastomosis reaches 17.7 % and stenoses -26.7 %, compared with plastic with wide gastric stem (3.5 and 8.3 %, respectively) [25]. And, as studies by this author have shown, the narrow isoperistaltic gastric stem shows insignificant motor activity due to the removal of parasympathetic intramural autonomic ganglia located with a small curvature. As a result, such plastics reduces patients quality of life due to the high frequency of reflux, regurgitation, aspiration and pneumonia, postoperative diarrhea, and especially the feeling of squeezing the sternum after eating.
Обговорюючи різні аспекти хірургії РС і ГЕР, необхідно висвітлити і питання комбінованих операцій, оскільки хворі з ІІ і Ш стадією складають до 85 % з числа оперованих. Висока частота місцево-поширених пухлин стравоходу нерідко змушує Esophageal plastics of the small intestine, proposed by C. Roux in 1907, was later improved and found wide application (especially in the treatment of esophagus cicatricial strictures in the first half of the twentieth century thanks to the work of P.A. Herzen, S.S. Yudin, A.A. Shalimov [26]. One of the significant disadvantages of esophageal plastic surgery of the small intestine is the exclusion of the most active part of the intestine from the digestive tract. Esophageal plastics require a length of intestine that corresponds to the length of the marginal vessel, which is equal to the length of the esophagus replacement area. Exclusion of the most active part of the small intestine has a negative effect on digestion (especially if it applies to the stomach). This causes fat malabsorption, which leads to serious metabolic disorders.
Among the disadvantages of coloesophagoplasty should be noted the following: more complex preoperative preparation, the likelihood of various diseases of the colon (polyps, ulcers, mesenteric atherosclerosis, etc.), technical complexity and long duration of surgery (taking into account the need to form at least 3 anastomoses). The restraint of surgeons in this matter is, of course, associated with the risk of anastomotic leaks or necrotic changes in the graft. Complications of this kind are fatal for the patient in the vast majority of cases.
The main advantages of colonic plasticity over gastric plasticity are preservation of the gastric phase of digestion and antireflux properties.
Many specialists use colonic plasticity in EC mainly due to the inability to perform gastric plastics due to the spread of the tumor to the proximal stomach or the so-called «compromised» stomach (peptic ulcer disease after gastrectomy period, gastrostomy with cross-section of the vascular arcade with great curvature) in primary and multiple cancers of the esophagus and stomach [27].
When discussing various aspects of EC and GEC surgery, it is necessary to cover the issues of combined operations, as up to 85 % of those operated are patients with stage II and III. The high incidence of locally advanced esophagus tumors often forces surgeons to perform combined operations (with resection of neighboring organs: lungs, pericardium, aorta, unpaired vein, liver, diaphragm, etc.). However, at morphological research of the removed specimen the real growth of a tumor in surrounding bodies is revealed only in 40-60 % of cases. This confirms the possibility of radical surgical treatment in other patients [28]. False-positive results are obtained mostly when assessing the invasion of the tumor in the pericardium, lung, atrium, pancreas.
Performing combined resections, when the surgeon found a tumor in the adjacent organs, during the operation is reasonable. In half of these situations, the operation can be radical. Otherwise, palliative resections are performed, which are discussed, but in some cases they are appropriate because they give patients a chance for further special treatment and, of course, improve their quality of life. The number of combined operations for esophageal cancer reaches 26.4 % [5].
Splenectomy is unfavorable factor for the prognosis of long-term results of surgical treatment of patients with EC and GEC. Research is currently carried out and data is already being published [31]. It is also well known that the spleen is the part of the reticuloendothelial system, destroys old red blood cells and platelets, it is also the main source of circulating lymphocytes, acts as a filter for bacteria, protozoa and produces antibodies. Moreover, splenectomy can lead to a 20 % increase in postoperative purulent-septic complications, such as subphrenic abscess, pancreatic fistula and pneumonia [32,33].
The incidence of postoperative complications in EC remains quite high and ranges from 45 to 62 % in different clinics. The peculiarity of this period is the change in the complications spectrum. Earlier the main fatal complication was the failure of the anastomosis, today this complication occupies one of the last ranks. Due to the expansion of the age range of the operated, the peculiarity of the contingent of patients with esophageal cancer is: old age, a large number of comorbidities on the background of a burdensome history and bad habits, alimentary and paraneoplastic depletion of patients. Thus, these factors determine the structure of complications and mortality. The leading place in the structure of postoperative complications is occupied by therapeutic ones: cardiovascular and pulmonary, they account for more than 60 % of all complications [34,35]. A common cardiovascular complication is cardiac arrhythmia.
Unilateral pneumonia is associated with prolonged lung collapse at the thoracic stage of the intervention. Another possible cause of pneumonia may be damage to the pulmonary branches of the vagus nerve with denervation of the lung root structures, which leads to increased permeability of the vascular wall.
Despite the use of anticoagulants of new generations, there is a stable pulmonary embolism, which often ends in fatal outcome.
There are rare complications: graft necrosis, bleeding from the stump of the stomach and anastomosis, bleeding into the pleural cavity. The twisting of the gastric graft around the axis should be mentioned as very severe complication.

CONCLUSIONS
Thus, surgical treatment remains the main strategic direction in EC and GER. Patients survival the primary goal of treatment.
A number of tactical issues that directly affect the outcome of treatment remain unresolved.
Special literature analysis indicates the expediency of performing thoracotomy and laparotomy in EC surgery, in GEC -oblique thoracophrenolaparotomy. The volume of lymph dissection in EC remains a key unresolved issue. At the same time, according to domestic and foreign surgeons specializing in the treatment of EC and GEC, dual-zone lymph dissection is a prerequisite for radical intervention in cancer of almost any prevalence. Performance of 3-zone lymph dissection finds less supporters, because its safety and oncological expediency have not been definitively studied.
The question of the need for splenectomy as a mandatory stage of lymph dissection D2 in GEC has recently been considered ambiguous due to dubious impact on the radicalism of the operation and, at the same time, the great negative consequences.
The recovery stage after esophageal resection is performed by most surgeons by forming an esophagealgastric anastomosis. Despite the significant decrease in the incidence of failure of this anastomosis in recent years, the technique of imposition is constantly improved in order to optimize the functional result and improve the quality of life of patients.

PROSPECTS FOR FURTHER RESEARCH
Based on the analysis of literature sources, we can conclude that today the issues of surgical techniques for esophageal cancer and gastroesophageal cancer remain relevant. Of particular relevance is the study of the possibility of using video-assisted surgical interventions.