A new philosophy in esophageal reconstruction with colon. Thirty-years experience

The author reports a personal series of 347 patients with colon interposition grafting as an esophageal substitute, the majority of them carried out for corrosive pharyngoesophageal strictures (284) followed by malignancy (54). A personal philosophy is exposed, based on increased flexibility in the choice of the type of colic interposition depending on the pattern of blood supply. This mobile policy called 'balanced operation' is opposed to the classic rigid approach based on the use of a single procedure of esophagocoloplasty. The author's choice is the ileocecum with long ileal loop (65 cm), favoring preservation of the ileocecal valve, and conferring an antireflux mechanism. In particular cases the cecum may be removed and an ileal graft carried out. If this arrangement is not feasible one should slide toward the left in a clockwise direction performing a left colon interposition (iso- or antiperistaltic). Overall mortality was of 16 cases (4.6%). Morbidity is analyzed and different particular arrangements like continuous colic loop, superlong graft, Roux-en-Y procedure are described. A general outline of pharyngeal reconstruction in corrosive strictures is presented.     

Left colonic graft in esophageal reconstruction for caustic stricture: mortality and morbidity

The adequacy of the blood supply to the left colon graft and its ability to transport food effectively from pharynx to stomach made it an esophageal substitute of choice, particularly in esophageal caustic stricture. From 1999 to 2009, 60 patients underwent colon interposition for esophageal caustic stricture (n= 57) and cancer (n= 3). An isoperistaltic colonic graft based on the left colonic artery could be used in all of these patients. The substernal route was used exclusively, and upper thoracic inlet was opened when necessary. The isoperistaltic left colonic graft interposed by substernal route represents the surgical procedure of choice in all operations performed for esophageal substitution during the study period. The operative mortality rate was 3.3%. A cervical fistula occurred in 10 patients (16.6%) and cervical anastomotic stricture in five patients (8.3%). Dilation was required in all the stricture of the esophageal colonic anastomosis with good response. The isoperistaltic left colic transplant supplied by the left colic pedicle is an excellent long‐term replacement organ for the esophageal caustic stenosis. When performed by experienced surgeons, the left isoperistaltic esophagocoloplasty is a satisfactory surgical method for esophageal reconstruction with acceptable early morbidity and good long‐term functional results.     

Prevention and management of complications after colon interposition for corrosive esophageal burns

SUMMARY. We present our experience in the management of complications after a colon interposition for corrosive esophageal burns. From April 1976 to December 2006, 85 patients with caustic esophageal burns were included in this study. The superior belly median incision with an anterior border incision of the left sternocleidomastoid was used. Anastomosis between the colon and the cervical esophagus was performed in 68 and between the colon and pharyngeal portion in 14 patients. An esophageal scar part resection and gastric‐esophageal anastomosis was performed in one patient who had been given an unsuccessful colon and jejunum interposition at another institute. An anastomotic modeling operation was performed in one patient with anastomotic stricture who had been managed with colon interposition at another institute. Exploratory thoracotomy and gastrostomy was performed in one patient who had an unsuccessful colon interposition at another institute. Seven of 14 patients (8.5% of 17.1%) died with serious complications such as aspirated pneumonia, interposition colon necrosis, abdominal wound dehiscence and degradation of swallowing and concordance function. However, others with such serious complications survived and were discharged for rehabilitation after corresponding treatment. The 25 patients (30.1%) with other mild complications were discharged for rehabilitation and corresponding management. Two patients from other institutes were discharged for rehabilitation and one was lost to follow‐up. The most dangerous complication of this procedure is colon necrosis, and the stomach is the best organ for re‐operation. Otherwise, aspiration in infants due to hypoplasia and degradation of swallowing co‐ordination needs attention. Peri‐operative management is very important, including the control of mediastinal and pulmonary infection and systemic nutritional support to avoid abdominal wound dehiscence. The platysma flap is an excellent method for the treatment of anastomotic stricture.     

Œsocoloplasties itératives pour sténoses caustiques de l’œsophage : place de la résection de l’articulation sternoclaviculaire

The colic graft necrosis is a redoubtable complication of the colon interposition for esophageal replacement. Its frequency varies from 1% to 22% according to the series. The restoring of the digestive continuity is a real problem. We report the observation of a 24-year-old patient admitted for a caustic stenosis of the esophagus, it was a long stenosis which was not dilatable; he underwent a colon interposition for esophageal replacement. Postoperative recoveries were labeled by the occurrence of a respiratory distress syndrome with fever on the second postoperative day. An injected scanner showed a proximal graft necrosis. The patient underwent a revision surgery with resection of 7 cms of necrosed colon, the rest of the graft was retained in the abdomen as a blind colostomy, and an esophagostomy was realized. We used the same graft for second reconstruction. The left clavicle’s head and the manubrium were resected to enlarge the thoracic inlet. The postoperative recoveries were simple. The aim of this work is to underline the difficulty of the second reconstruction in case of necrosis of the colic graft which can require complex surgical procedures and the contribution of the resection of the clavicle’s head and the manubrium, which can allow the use of the same graft.     

Anterior vs. Posterior Mediastinal Routes in Colon Interposition after Esophagectomy

Background/Aims: Colon interposition is the most commonly used method of esophageal reconstruction when the stomach cannot be used; however, this method may cause surgical complications such as anastomotic leakage and sepsis due to colon necrosis. Therefore, many surgeons use a retrosternal or subcutaneous route because it is easier to manage the subcutaneous drainage when anastomotic leakage occurs. However, some researchers have reported that the posterior mediastinal route provides better long-term functional outcomes after surgery than the anterior mediastinal route. Thus, in this study, we compared these reconstruction routes used for colon interposition, with or without the supercharge technique, in patients with a history of distal gastrectomy, who have undergone colon interposition after esophagectomy. Methodology: We retrospectively studied 30 patients who underwent esophagectomy with colon interposition. These patients were divided into 2 groups based on the reconstruction route: the anterior mediastinal or subcutaneous route (A group), or the posterior mediastinal route (R group). Results: Anastomotic leakages were observed in 4 patients (26.7%) in the A group and in 1 patient (6.7%) in the R group. Conclusions: Ischemia is not always the result of arterial failure, but may also originate from venous blood flow impairment due to injury or distortion of veins.     

Surgical management of corrosive strictures of stomach.

BACKGROUND: Corrosive injuries of the upper aero-digestive tract are a frequent cause of morbidity in India. We report here our institution's experience in managing patients with corrosive strictures of the stomach. METHODS: Records of 28 patients who underwent definitive surgery for corrosive strictures of the stomach in our institution over a 15-year period were reviewed. RESULTS: The main presenting complaints were vomiting (75%), dysphagia (46%) and significant weight loss (100%). Pre-operative evaluation included barium and endoscopic studies. Most patients had antro-pyloric strictures (n=22); in 6 patients, however, near-total or total gastric involvement was observed. Thirteen (46%) patients had associated strictures of the esophagus; of these, 7 responded to esophageal dilation. Strictures of the stomach were managed with resectional procedures like distal gastrectomy (n=16), subtotal gastrectomy (1) or total gastrectomy (3) and esophagogastrectomy (1) in 21 (75%) patients. The remaining 7 patients underwent bypass procedures like gastrojejunostomy (5), stricturoplasty (1), and colonic bypass of esophagus and stomach (1). Three patients had entero-cutaneous fistulae in the postoperative period. One patient died in hospital of septicemia and malnutrition. CONCLUSIONS: In patients with corrosive strictures of the stomach, surgery, tailored according to the extent of gastric involvement and presence of associated esophageal strictures, gives excellent results.     

Caustic injury of the upper gastrointestinal tract: A comprehensive review

Prevention has a paramount role in reducing the incidence of corrosive ingestion especially in children, yet this goal is far from being reached in developing countries, where such injuries are largely unreported and their true prevalence simply cannot be extrapolated from random articles or personal experience. The specific pathophysiologic mechanisms are becoming better understood and may have a role in the future management and prevention of long-term consequences, such as esophageal strictures. Whereas the mainstay of diagnosis is considered upper gastrointestinal endoscopy, computed tomography and ultrasound are gaining a more significant role, especially in addressing the need for emergency surgery, whose morbidity and mortality remains high even in the best hands. The need to perform emergency surgery has a persistent long-term negative impact both on survival and functional outcome. Medical or endoscopic prevention of stricture is debatable, yet esophageal stents, absorbable or not, show promising data. Dilatation is the first therapeutic option for strictures and bougies should be considered especially for long, multiple and tortuous narrowing. It is crucial to avoid malnutrition, especially in developingcountries where management strategies are influenced by malnutrition and poor clinical conditions. Late reconstructive surgery, mainly using colon transposition, offers the best results in referral centers, either in children or adults, but such a difficult surgical procedure is often unavailable in developing countries. Possible late development of esophageal cancer, though probably overemphasized, entails careful and long-term endoscopic screening.     

Surgical management of esophageal strictures after caustic burns： A 30 years of experience

AIM: To analyze a 30-year historical series of patients treated in our hospital, who ingested corrosive substances, and to assess the effectiveness of surgical therapy administered in patients with strictures after caustic injury in esophagus during this period. METHODS: A total of 79 cases of caustic burns in esophagus were treated in Tangdu Hospital from 1971 to 2001. Their clinical and pathological data were reviewed, and collected from the medical records of patients and interviews with them. RESULTS: More men (n = 61) than women (n = 18) ingested caustic substances with a sex ratio of 3.4:1 during the 30-year period. The caustic materials were liquid lye and acids (54 cases and 25 cases, respectively). Sixty-eight patients were given esophageal replacement in more than three months after caustic injury with no postoperative death, of which 17 cases developed postoperative complications making a complication rate of 25%. The most common one was cervical anastomotic leakage. All patients had improvement in swallowing afterwards. CONCLUSION: The presence and severity of injuries are correlated with the amount of caustic substances ingested. Surgical treatment is a good option in patients with severe strictures, and colonic interposition might be the best surgical process. The most important factors to guarantee a successful outcome for surgery are good vascular supply and absence of tension in the anastomosis.     

Esophageal replacement by colon interposition with microvascular surgery for patients with thoracic esophageal cancer: the utility of superdrainage

Replacing the thoracic esophagus with the colon is one mode of reconstruction after esophagectomy for esophageal cancer. There is, however, a high incidence of postoperative necrosis of the transposed colon. This study evaluated the outcomes of colon interposition with the routine use of superdrainage by microvascular surgery. Twenty‐one patients underwent colon interposition from 2004 to 2009. The strategy for colon interposition was to: (i) use the right hemicolon; (ii) reconstruct via the subcutaneous route; (iii) perform a microvascular venous anastomosis for all patients; and (iv) perform a microvascular arterial anastomosis when the arterial blood flow was insufficient. The clinicopathologic features, surgical findings, and outcomes were investigated. The colon was used because of a previous gastrectomy in 18 patients (85.7%) and synchronous gastric cancer in three patients (14.3%). Eight patients (38.1%) underwent preoperative chemoradiotherapy including three (14.3%) treated with definitive chemoradiotherapy. Seven patients (33.3%) underwent microvascular arterial anastomosis to supplement the right colon blood supply. Pneumonia occurred in four patients (19.0%). Anastomotic leakage was observed in five patients (23.8%); however, no colon necrosis was observed. The 3‐year and 5‐year overall survival rates were both 50.6%. Colon interposition with superdrainage results in successful treatment outcomes. This technique is one option for colon interposition employing the right hemicolon.     

Surgical treatment and clinical course of patients with hypopharyngeal carcinoma

In the period between 1 January 1978 and 1 January 2004, 85 patients with hypopharyngeal squamocellular carcinoma were admitted at the Department of Esophagogastric Surgery in Belgrade. Among them, only 46 patients (54.1%) had radical surgical en-block resection and functional neck dissection, and they were included into an historical cohort study. In 40 patients a pharyngolaryngoesophagectomy was performed using for reconstruction, stomach tissue in 29 and colon tissue in 11 patients. Since 1996, in six patients with localized hypopharyngeal carcinoma pharyngolaryngectomy was performed with resection of cervical esophagus and free jejunal graft interposition. The overall incidence of morbidity was 50.0% and the overall mortality rate was 13.0% (6 patients). Mean hospital stay was 35 days (range, 18-78 days). The median survival of patients was 26 months, and overall 5-year survival rate was 26.5%. At present, surgery seems to be the appropriate therapeutic choice for patients with advanced hypopharyngeal carcinoma, providing a definitive palliation of dysphagia and relatively good long-term survival. At our Institution, after pharyngolaryngoesophagectomy, reconstructive method of choice is gastric 'pull-up', and the colon is used only when stomach tissue is not available, that is, previous gastric resections, inappropriate blood supply, synchronous gastric carcinoma and so on. Recently, pharyngolaryngectomy and free jejunal transfer has become the standard technique in patients with small carcinomas (up to 3 cm) confined to the hypopharynx in the absence of synchronous esophageal and/or gastric carcinoma.     

Functional Outcome of Gastrointestinal Tract and Quality of Life After Esophageal Reconstruction of Esophagus Cancer

Background/Aim:

Information about functional outcome and quality of life after esophagectomy and esophageal reconstruction (ER) for the treatment of esophageal cancer, as evaluated by the patients themselves is limited. We aimed to study the post-surgical outcome of such patients to detect for the development of any complications that may arise from the surgery as well as to evaluate their quality of life following the surgery.

Methods:

From 1993 to 2003, 240 patients with stage I, II, or III esophageal carcinoma underwent esophagectomy at Razi Teaching Hospital located in the north of Iran. Of these, 192 patients filled out a questionnaire during a 2-year period (ranging from 12 to 48 months after surgical reconstruction). Among them, there were 134 men (69%) and 58 women (31%), and the mean age at the time of ER was 48 years (ranging from 22 to 75 years). Transhiatal esophagectomy, extended esophagectomy (three field operation), and Ivor-Lewis resection were done in 142 (73.95%), 30 (15.62%), and 20 patients (10.42%), respectively. Intestinal continuity after esophageal resection was established with stomach in 154 patients (80%), colon in 28 patients (14%), and small bowel in 10 patients (5.2%). Cervical anastomosis was established in 172 patients (89.6%), while intrathoracic anastomosis was performed in 20 patients (10.4%).

Results:

After ER, 66 patients (34.4%) suffered from dysphagia to solids and 50 patients (26%) required at least one or three postoperative dilatations for alleviation of symptoms. Gastroesophageal reflux was seen in 32 patients (16.66%) and was more common in thoracic anastomosis patients than in cervical anastomosis patients. Heartburn was present in 33 cases (17%), 30 of whom required medication (37%). The number of meals per day was three to four in 116 patients (60%), more than four in 51 patients (29%), and less than three in 19 patients (9.82%). The number of bowel movement per day increased in 52 patients (27%), decreased in 60 cases (31%), and unchanged in 80 patients (41%). Weight gain was reported by 38 patients (19.8%), and weight loss was reported by 50 patients (26%). No change in weight occurred in 100 patients (52%). Overall satisfaction was excellent in 29 patients (15%). Overall quality of life (work, pain-relief, vitality, and emotional status) was lower than in general population. Age, sex, and stage of cancer did not affect the functional outcome but affected the quality of life. Also patients who received cervical anastomosis and ER with colon had significantly fewer reflux symptoms. Most of the patients with colon reconstruction gained weight.

Conclusions:

Self-assessment of postoperative ER by the patients after esophagectomy for malignant disease demonstrates that undesirable symptoms are frequently present at short- and long-term follow-ups. Short- and long-term functional outcome is affected by the type of reconstruction after esophagectomy. Results of this study suggest that colon graft in ER is significantly advantageous compared with other methods because of the ability of patients to gain weight and avoid developing postoperative reflux.     

German experience with colon interposition grafting as an esophageal substitute.

Preliminary results of a questionnaire survey showed that gastric transposition is the technique of choice in Germany to restore alimentary continuity after esophageal resection. Experience with colon interposition grafting is low. Only 13% of all centers perform this technique. Despite this limited experience, there appears to be no difference in the complication rate between gastric pull-through procedures and colon interpositions. A modification of established colon interposition techniques is possible when the right colon is used if it is prepared in such a way that the left colonic artery is the blood supplying vessel. This modified technique may be simpler to perform than previous procedures for creating a colon interposition graft and may also facilitate esophageal replacement using colon interposition grafting.     

Is the surgical stress associated with worse survival in patients with esophageal cancer?--Analysis of colon substitution for 37 patients with remnant stomach

BACKGROUND/AIMS: Colon substitution is a standard method of reconstruction, although an aggressive surgery, for patients with esophageal carcinoma who have remnant stomach. Presence of postoperative complication was reported to be a risk factor for worse survival in the patients with esophageal cancer. We evaluated the affect of this surgical stress on the postoperative course and long-term survival of patients with esophageal carcinoma. METHODOLOGY: Between 1980 and 2002, a total of 37 patients with primary thoracic esophageal squamous cell carcinoma, who had history of gastrectomy due to gastric ulcer, underwent R0 esophagectomy followed by colon substitution (colon group). The clinical affect of colon substitution was retrospectively evaluated in comparison with gastric substitution as the control group (stomach group). RESULTS: The postoperative hospital morbidity rate was significantly higher in the patients with remnant stomach than in the control group. Although the clinicopathological features in both groups were similar, except operative time and bleeding volume, the overall and cause-specific survival of the remnant stomach group were significantly worse than those of the control group. Multivariate analysis suggested that remnant stomach was an independent risk factor for a worse survival. CONCLUSIONS: Surgical stress and postoperative complications, resulted by colon substitution for the patients with remnant stomach, might be associated with worse survival of patients with esophageal cancer.     

Anastomotic false aneurysms after under-diaphragmatic bypasses: about 25 cases

The purpose of our study is to determine the causes and the management of anastomotic aneurysms. We report the cases of 25 patients with a mean age of 64 years at the time of initial surgical revascularisation. The mean interval between the first operation and the occurrence of anastomotic aneurysm is 5 years (range 2 months-11 years). The treatment consists on the interposition of a graft in 8 patients, anastomotic angioplasty in 9 patients and the reconstruction of the anastomosis in 8 patients. Hospital mortality was 20%. Late death occurs 3 patients and the long-term morbidity was evaluated at 22%. A recurrence of anastomotic false aneurysm occurred in 4 patients (16%) (Range 7 months-1 year). In conclusion anastomotic false aneurysm is one of the major complications of vascular reconstruction; careful follow-up can detect the rare instances of anastomotic aneurysm and reoperation can be accomplished with a low-rate of adverse outcome.     

Self-bougienage: long-term relief of corrosive esophageal strictures.

BACKGROUND: Corrosive esophageal strictures require dilatation at frequent intervals. OBJECTIVE: To determine the efficacy of self-dilatation in treatment of corrosive esophageal strictures. METHODS: Retrospective analysis of data from 51 patients with corrosive esophageal strictures seen in a surgical unit. Eighteen patients underwent per-oral antegrade dilatation of stricture using gum elastic bougies (Group I); 15 patients underwent retrograde dilatation with endless string using an India rubber dilator devised at the authors' institution, followed by per-oral antegrade dilatation (Group II); 15 patients underwent retrograde dilatation followed by antegrade dilatation with endless string through esophagostomy (Group III). In three patients with stricture of the entire esophagus, endless string could not be passed; they were subjected to esophagocoloplasty. All patients were taught self-dilatation with gum elastic bougies as the final step, and were put on a progressive, domiciliary, self-dilatation program. Quarterly follow up was done for one year, to ascertain whether self-bougienage was being performed properly. RESULTS: All patients responded well to treatment, with significant relief of dysphagia and improvement in health and barium study findings. Six patients developed mediastinitis (3, 2 and 1 in Groups I, II and III, respectively) during initial dilatation; all improved with conservative management. Only one patient who failed to carry out self-bougienage had to be readmitted and retrained in the procedure, after which he remained asymptomatic. CONCLUSIONS: Patients with corrosive esophageal strictures can be treated with a long-term self-bougienage program, which avoids the need for frequent hospital admissions for esophageal dilatation.     

Benign esophageal strictures in infants and children: results of Savary-Gilliard bougie dilation in 107 Indian children

BACKGROUND: Little information is available regarding the safety and efficacy of dilation of esophageal strictures in children with Savary-Gilliard bougies. This is a report of our experience with this form of dilation in Indian children. METHODS: One hundred seven Indian children age 14 years or younger with benign esophageal strictures underwent dilation. Clinical information including etiology was recorded. Dilation was performed at 2- to 3-week intervals by using Savary-Gilliard bougies under ketamine sedation and was considered adequate if the esophageal lumen could be dilated to 15 mm diameter (12.8 mm in children <5 years of age) with complete relief of symptoms. Subsequently, dilation was performed on an "as needed" basis. RESULTS: Mean age was 4.8 +/- 3.4 years; male to female ratio was 3:1. Fifty-four children had corrosive strictures (acid 34, alkali 20). Noncorrosive strictures were sclerotherapy-induced (23), postsurgical (14), congenital (10), peptic (4), and due to other causes (2). Dilation was successful in all but 3 cases. Corrosive strictures required a significantly higher number of sessions to achieve adequate initial dilation (2.4 +/- 1.9 vs. 1.3 +/- 0.5, p < 0.01). Patients with corrosive strictures also required a higher number of subsequent sessions for recurrence (7.3 +/- 6.5 vs. 0.7 +/- 1.3, p = 0.10). Dilation was also successful in patients with strictures 5 cm or more in length and/or patients with multiple corrosive strictures, although these required a higher number of sessions to achieve adequate dilation (p < 0.05) and also higher number of subsequent sessions for recurrence. Six esophageal perforations occurred during 648 dilation sessions (0.9%); 5 occurred in patients with corrosive strictures. One patient required surgery. CONCLUSIONS: Corrosive injury is the most common cause of benign esophageal strictures in Indian children. Savary-Gilliard bougie dilation is safe and effective, even for long and/or multiple corrosive strictures.     

Surgical outcomes of oro-intestinal continuity reconstruction after total esophagectomy in patients with cervicothoracic malignancy: a thoracic surgeon’s perspective

BackgroundOro-intestinal continuity reconstruction following total esophagectomy in patients with head-neck or esophageal cancer is rare and results in high operative morbidity and mortality. This case series aimed to investigate the perioperative surgical outcomes of oro-intestinal continuity reconstruction after total esophagectomy in selected patients with advanced head/neck or esophageal cancer.MethodsFrom 2011 to 2018, 14 patients who underwent oro-intestinal reconstruction after total esophagectomy were assessed. We analyzed perioperative mortality, postoperative complications, oncologic outcomes, and recovery of dietary function.ResultsThe median age of the patients was 61 (range, 42–72) years old and median follow-up time was 18.6 (range, 0–52.9) months. For conduit selection, 11 cases of oro-gastrostomy (78.6%), 2 of oro-colo-gastrostomy (14.3%), and 1 of oro-jejuno-gastrostomy (7.1%) were performed. Complete resection was pathologically confirmed in 10 patients (71.4%). Anastomosis site leakage was observed in three patients (21.4%) and conduit necrosis in two (14.3%). Postoperative mortality within 30 days, 90 days, and 1 year was 7.1%, 28.6%, and 42.8%, respectively.ConclusionsOro-intestinal continuity reconstruction following total esophagectomy showed acceptable morbidity and mortality in selected patients with advanced head/neck cancer or esophageal cancer. Careful selection of surgical candidates and multidisciplinary collaboration of experienced surgical teams are essential to minimize the surgical risk.     

Intestinal interposition for benign esophageal disease

Opinion statement Various options exist for intestinal interposition for benign, but debilitating, end-stage esophageal disorders. Principally, the stomach, colon, or jejunum is used for esophageal replacement. Much debate exists regarding the ideal esophageal replacement option. The conduit choice must be tailored to the individual patient. Unlike malignant processes, the conduit choice for benign disorders must be sufficiently durable and functional. Colonic interposition meets both criteria. However, this operative procedure’s technical difficulty increases the complexity of this already challenging clinical problem, as seemingly small errors in judgment and technique can significantly impact graft viability and long-term function. Using a gastric tube also provides durability and functionality, but with an operative procedure that is less technically demanding. A minimally invasive laparoscopic transhiatal esophagectomy offers the patient even more benefit in terms of shorter operative times and intensive care unit and recovery periods. However, the advent of surgical robotic technology augments these benefits even further. Robotic technology arms the surgeon with improved dexterity and three-dimensional visualization. These revolutionary improvements allow the surgeon to overcome many of the operative limitations that exist with the open and minimally invasive approaches to esophagectomy, thus potentially offering patients reduced morbidity and mortality rates.     

Late dysphagia after presternal colon interposition

Esophageal replacement by colon interposition is done for a variety of esophageal diseases. Dysphagia occasionally develops many years after successful colon interposition. Redundancy of the colon graft is usually responsible. We report a patient with onset of dysphagia 24 years after presternal colon interposition for long segment esophageal atresia. Pathophysiology, prevention, and treatment of late colon interposition dysfunction are discussed.