Aetiopathogenesis Types, Investigations and Treatment

Nutcracker Oesophagus Or Jackhammer Oesophagus

Aetiology is not known. Chest pain is the most common symptom followed by painful dysphagia (odynophagia). Barium swallow is usually normal. An epinephrine diverticulum is usually present.

Majority of the patients have normal propagation of peristaltic waves. However, in the distal oesophagus, peristaltic waves have very high amplitude (>180 mmHg) and duration (>6 seconds). Dilatation, myotomy, proton pump inhibitors, calcium channel blockers are used with limited success. Requrgitation and reflux are uncommon.

Describe the clinical features, investigations and principles of management of benign and malignant disorders of oesophagus.

Read And Learn More: Gastrointestinal Surgery Notes

Carcinoma Of The Oesophagus

Carcinoma Of The Oesophagus Introduction: Majority of oesophageal cancers are squamous cell carcinomas, worldwide. However, in most Western countries, more than 70% are adenocarcinomas. This shift is mainly due to smoking, alcohol and Barrett’s oesophagus. More than 50% of patients present with locally advanced carcinomas. Some improvement has taken place now because of early diagnosis, detection and multimodality treatment.

Oesophageal cancers have poor prognosis because of the following reasons

• More lymph vessels are present in the submucosa than blood capillaries and hence, spread is fast.
• Lymph flow in submucosal plexus runs in a longitudinal direction. Hence, primary tumour can extend for a considerable length both superiorly and inferiorly.
• Cervical oesophagus has direct spread to regional nodes and there are less lymphatics in the submucosa. Hence, prognosis is better.

What is the ‘Change’ in Carcinoma Oesophagus? Squamous cell carcinoma is more common in Africans and Asians. Adenocarcinoma is more common in whites and Americans. Adenocarcinoma is increasing

Aetiopathogenesis

1. Precancerous or Predisposing Conditions
   • GORD with Barrett’s oesophagus. Malignancy in Barrett’s oesophagus is curable if detected at an early stage. Hence, endoscopic surveillance is recommended.
   • Plummer-Vinson syndrome with squamous metaplasia—upper oesophagus.
   • Achalasia cardia —lower oesophagus.
   • Corrosive strictures. Lye strictures up to 30%: Squamous cell carcinomas may arise in lye strictures, often developing 40-50 years after caustic injury. The majority of these cancers are located in the middle third of the oesophagus.
2. Carcinogens
   • Tobacco, heavy smoking and abuse of alcohol increase incidence of both squamous cell carcinoma and adenocarcinoma by almost 20-25%.
   • Dietary carcinogens and squamous cell carcinoma
     • Elevated nitrates in drinking water.
     • Food (pickles, corn) containing fungi—Geotrichum candidum as in endemic areas of China.
     • Baked bread
3. Viral: Human papillomavirus (HPV) infection increases squamous cell carcinoma. This oncogenic virus has been associated with cervical and oropharyngeal cancers also.
4. Hereditary:
   • Hovels-Evans syndrome or tylosis—40-60% of the patient develops cancers. Also called familial keratosis plantaris.
   • Tylosis (focal nonepidermolytic palmoplantar kerato-derma) is a rare disease inherited in an autosomal dominant manner that is characterised by hyperkeratosis of the palms and soles and oesophageal papillomas. Patients with this condition exhibit abnormal maturation of squamous cells.
   • They also cause inflammation within the oesophagus and are at extremely high risk of developing oesophageal cancer.
   • Patients with head and neck cancers—field cancerisa tion.
5. Bacterial
   • Helicobacter pylori infection: Infection with Helicobacter pylori, and particularly with cag A+ strains, is inversely associated with the risk of adenocarcinoma of the oesophagus.
   • Mechanism is not clear. In fact, it should not have been a factor responsible because H. pylori infection can cause chronic atrophic gastritis leading to decreased acid production, which negates the effects of chronic reflux, including the potential for development of Barrett’s oesophagus.
6. Miscellaneous
   • Factors for adenocarcinoma
     • Obesity: Increased body mass index is a risk factor for adenocarcinoma of the oesophagus, and individuals with the highest body mass index have up to a seven-fold greater risk of oesophageal cancer than those with a low body mass index. Probably, the linkage between obesity and gastro-oesophageal reflux disease is presumed to be a chief factor.
     • Economic status: Low socioeconomic status as defined by income, education, or occupation is associated with increased risk for oesophageal squamous cell carcinoma, and adenocarcinoma to a smaller extent.

Aetiopathogenesis Sites

• 50%—middle 1/3rd of oesophagus
• 33%—lower 1/3rd of oesophagus
• 17%—upper 1/3rd of oesophagus.

Aetiopathogenesis Types

1. Squamous Cell Carcinoma Types
   • Epitheliomatous ulcer (carcinomatous) with raised edges and flat base.
   • Proliferative growth (cauliflower) with surface ulcer which commonly bleeds.
   • Infiltrative variety or annular stenosing variety with a 5-year survival of 10%, gives rise to early dysphagia due to circumferential and longitudinal spread.
   • Polypoidal lesions (5 years survival 70%).
2. Adenocarcinoma: Mostly lower end and middle oesophagus (in Barrett’s oesophagus). Comparison of squamous cell carcinoma and adenocarcinoma is given in Table.

Aetiopathogenesis Clinical Features

• Men more than 60 years.
• Dysphagia which is progressive and mainly for solids (it takes 18 months for dysphagia to develop). It means 60% of the circumference of the lumen is involved by the growth. By the time, the patient presents with dysphagia, the disease is fairly advanced. Hence, it has a poor prognosis. Dysphagia is a late symptom because smooth muscle of oesophageal wall can dilate with ease due to lack of serosal layer on the oesophagus.
• Regurgitation of the food contents. Haematemesis is not very common. Vomitus may contain streaks of blood and melaena is rare.
• Loss of appetite, loss of weight and cachexia
• Backache indicates enlarged lymph nodes (coeliac).

Aetiopathogenesis Spread

1. Local Spread ort direct spread
   • To start with, it is a mucosal ulceration which spreads edges and flat base. to the submucosa. Later, it causes fibrosis and the lumen gets narrowed. The spread occurs transversely and longitudinally. Once it spreads to all the layers, the structures in the vicinity are involved.
   • Factors Responsible for Early Spread and Aggressive Behaviour of Carcinoma Oesophagus are lack of serosal layer, proximity of vital structures, extensive mediastinal lymphatic drainage and late presentation.
   • When the trachea is involved, tracheo-oesophageal fistula develops from carcinoma upper 1/3rd of oesophagus.
   • Broncho-oesophageal fistula from carcinoma middle 1/3rd.
   • Oesophagoaortic fistula results in massive bleeding (one of the causes of death).
   • All these complications are contraindications for surgery and radiotherapy.
2. Lymphatic Spread: Studies have showed that patients having metastasis to 5 or fewer lymph nodes have a better outcome. Palpable left supraclavicular nodes indicate advanced disease. This sign is described as Troisier’s sign.
3. Blood Spread: It results in secondaries in the liver, which clinically appear as nodular enlarged liver. Later, ascites and rectovesical deposits occur.

Aetiopathogenesis Investigations

1. Hb% is low, which is the cause of generalized weak¬ness.
2. Liver function test (LFT) is affected, if secondaries in liver occur (increased ALP).
3. Ultrasound is done to rule out liver secondaries, lymph nodes in the porta hepatis, coeliac nodes, etc.
4. Barium swallow demonstrates irregular, persistent, intrinsic filling defect (Figs 40.24 to 40.27)— shouldering is characteristic. Barium can also detect abnormal ‘axis’. It can also demonstrate fistula. Both these features suggest that ‘CURE’ is not possible.
5. Oesophagoscopy to visualise the growth and to take biopsy. Multiple biopsies may be necessary. In high-risk areas like China, endoscopic staining with supra-vital dyes (indigocarmine) is done to identify dysplastic epithelium. If found, some advocate endoscopic mucosal resection.
6. Chest X-ray to rule out aspiration pneumonia, media¬stinal widening and posterior tracheal indentation.
7. Bronchoscopy to rule out involvement of bronchus, as in carcinoma middle 1/3rd. If involved, it can confirm that tumour is locally unresectable.
8. CT scan of the chest and abdomen to detect local infiltration and to stage the disease. It is a very useful investigation before contemplating for total oesophagectomy. It is useful to assess involvement of vital structures such as bronchus, airway, pericardium, aorta, etc. Obliteration of fat planes gives the clue.
9. Endoscopic ultrasound to know the depth of wall involvement, to detect mediastinal lymph nodes, etc.
10. Positron emission tomography (PET)/compu¬terized tomography scanning: PET scan is based on the principle that metabolically active tumour cells can be visible once radiopharmaceutical agent 18F-fluorodeoxyglucose (FDG) is given intrave-nously. These lymph nodes, if malignant, are clearly visible thus differentiating them from nonmalig-nant enlargement. Applying the same principles, PET can be used to know the ‘response’ after radiotherapy or chemotherapy.
11. Thoracoscopy and laparoscopy: At the end of all investigations, it is important to decide, whether one can resect this tumour or not? Is it worthwhile resecting? Can patient tolerate the procedure? Is palliative majoe resections worth doing? Even in the absence of systemic spread, some features will suggest surgical cure is unlikely. Check these key boxes.
12. Laparoscopic ultrasound: It is an extended investigation.

Aetiopathogenesis Chromoendoscopy

• Chromoendoscopy involves the topical application of stains or pigments to improve tissue localisation, characterisation, or diagnosis during endoscopy.
• Several agents have been described that can broadly be categorised as absorptive (vital) stains, contrast stains, and reactive stains.
• Absorptive stains (for example, Lugol’s solution and methylene blue) diffuse or are preferentially absorbed across specific epithelial cell membranes.
• Contrast stains (for example, indigocarmine) highlight surface topography and mucosal irregularities by permeating mucosal crevices.
• Reactive stains (for example, Congo red and phenol red) undergo chemical reactions with specific cellular constituents, resulting in a colour change.

Aetiopathogenesis Endoscopic Ultrasound (Endosonography)

• It relies on a high frequency (5-30 MHz) transducer
• To determine the depth of spread of a malignant tumour through the oesophageal wall
• Involvement of adjacent organs o Metastasis to lymph nodes
• Also detects contiguous spread downward into cardia
• Can detect metastasis in the liver
• Can also detect small lymph nodes which are less than 5 mm (which cannot be detected by CT scan)
• If ‘endosonography’ detects more than 5 lymph nodes, it is not a case for curative resection.

Aetiopathogenesis Investigations and their Importance in Carcinoma Oesophagus

• Haemoglobin: If it is low, wound healing is delayed
• Albumin: If it is low, anastomotic leak rates are high
• Barium studies: Straight axis of oesophagus indicates inoperability Fistula can be detected
• Chest X-ray: If it shows coin lesions, it is an advanced disease
• Bronchoscopy: Infiltration of bronchus indicates inoperability
• CT scan: Investigation of choice, helps in deciding the type of treatment
• Endosonography: To know the involvement of different layers of oesophagus for TNM staging
• PET scan: Is not done in the initial stage for evaluation, done for recurrent disease.
• Diagnostic laparoscopy before radical surgery, if perito¬neal metastases are present—avoid radical surgery

Aetiopathogenesis Thoracoscopy and Laparoscopy

• Staging tools in oesophageal cancer.
• More accurate in determining nodal status than non-invasive techniques and helpful in evaluating the extent of local invasion and metastatic disease.
• Thoracoscopy is accurate in 93% and laparoscopy in 94% of patients in identifying metastatic disease.
• Studies have proved that 6 cases of unsuspected coeliac nodal disease were identified in 19 patients despite preoperative CT and EUS.

Aetiopathogenesis Unlikely Surgical Cure in the Absence of Systemic Spread

• Loss of weight more than 20%
• (O)Esophageal ‘axis’ is abnormal on barium test
• Nodes—multiple on CT scan
• Grade—invasive, poorly differentiated
• Tumour length more than 8 cm
• Horner’s syndrome Remember as LENGTH

Aetiopathogenesis Laparoscopic Ultrasound (LUS)

• LUS is also a staging modality and may provide improved accuracy in T and N staging.
• LUS may also be more accurate for staging coeliac nodes because EUS probe is more distant and does not provide direct inspection.
• Depth of invasion
  • For T1 lesions, conservative oesophageal resection such as vagal-sparing, transmittal or minimally invasive oesophagectomy can be opted.
  • For localised intramucosal tumours of limited extent, EMR or ESD are an acceptable alternative.
  • There is almost no role for chemoradiotherapy for the treatment of T1 lesions.
  • Surgical or endoscopic resection alone carries a good long-term survival, as high as 88% in some series.
• Depth of tumour vs lymph node involvement (LNI)
  1. T1 lesion (intramucosal) 18% LNI
  2. T1 lesion (submucosal) 55% LNI
  3. T2 lesion 60% LNI
  4. T3 lesion 80% LNI

Aetiopathogenesis General Assessment for Staging

• Once the diagnosis is confirmed and staging (TNM) is done by metastatic work-up, performance status is done by using ECOG (Eastern Cooperative Oncology Group) criteria.
• General health of the patient, co-morbid conditions, fitness for anaesthesia—all these factors decide the choice of therapy.

Treatment With Curative Intent

• Once diagnosis and accurate staging is done, the histological diagnosis is also considered for treating carcinoma oesophagus.
• Incidence of lymph node positivity is around 5% even when the disease is confined to the submucosal region— early cases.
• Tumour location is also important because of close proximity of oesophagus to pleura, pericardium azygos vein, aorta, etc.

While treating, cancers in the oesophagus can be broadly classified as follows:

• Cervical oesophagus: It is from hypopharynx to the thoracic inlet (at sternal notch), upper, thoracic oesophagus is from thoracic inlet to azygos vein.
• Midthoracic oesophagus tumours arise from lower border of azygos vein to inferior pulmonary vein (IMV).
• Lower oesophageal tumours distal (IMV) to gastro- oesophageal junction.

Treatment With Curative Intent TNM Staging

• Tumour
  • T0 No primary tumour
  • Tis Carcinoma in situ—high-grade dysplasia T1a Tu mour invades lamina propria, muscularis mucosa
  • T1b Tumour involving submucosa
  • T2 Tumour involving muscularis propria
  • T3 Tumour with para esophageal spread
  • T4 Involvement of recurrent laryngeal nerve, phrenic nerve, sympathetic chain, azygos vein; malignant effusion (adjacent structures)
  • T4a Resectable structure
  • T4b Tumor invades unresectable structure
• Nodal Status
  • Nx Lymph nodes cannot be assessed
  • N0 No regional lymph node metastasis
  • N1 Regional lymph node metastasis—1 to 2 nodes
  • N2 Metastasis in 3-6 regional nodes
  • N3 Metastasis in 7 or more regional nodes
• Metastasis
  • M0 No distal spread
  • M1 Upper thoracic oesophageal carcinoma with spread to other nonregional nodes or distant spread. Middle thoracic oesophageal carcinoma with spread to neck nodes/coeliac nodes or other nonregional nodes. Lower thoracic oesophageal carcinoma with spread to other nonregional nodes or distant spread.
  • Mx Distant metastasis cannot be assessed.
• TNM Stage Grouping
  • Stage 0: Tis N0 M0
  • Stage 1: T1 N0 M0
  • Stage 2A: T2 N0 M0, T3 N0H0
  • Stage 2B : T1N1N0, T2N1, M0
  • Stage 3 : T3N1M0, T4 and N1N0
  • Stage 4: A—Any T and N, M1 a B—Any T1 and N, M1 b

1. Carcinoma Cervical and Upper Thoracic Oesophagus
   • In vast majority of cases, treatment of carcinoma oesophagus is aimed at to relieve dysphagia by palliative resection/palliative radiotherapy/metallic stenting.
   • Tumours that have not penetrated through oesophageal wall and have not metastasised to regional lymph nodes are potentially curable.
   • Decision of surgery/radiotherapy also depends upon location of the tumour, histology, site of the tumour, staging and cardiopulmonary reserve. Nutritional status has to be improved to raise albumin levels from 3 to 3.4 g/dl to decrease complications such as anastomotic leak.
   • Cervical oesophageal cancers are almost always squamous cell carcinomas. Usually they are postcricoid in a female patient. It is very unusual for this malignancy to involve intrathoracic nodes. Upper thoracic is also squamous cell carcinoma. Involve¬ment of thoracic nodes, and early spread to trachea, bronchus and great vessels is common.
   • Surgery followed by radiotherapy is the treatment of choice. Local recurrence is high and they succumb to local disease.
   • If adjacent structure is not involved, total oesophageectomy with or without laryngectomy can be done. Pre¬operative neoadjuvant chemotherapy can also be given first (2-3 cycles followed by 3-5 Gy of radiation therapy).
   • This is followed by total laryngectomy with bilateral neck dissection and reconstruction using gastric pull-up.
   • Tumours in the upper thoracic oesophagus are removed by posterolateral thoracotomy, excision of the tumour and lymph nodes followed by gastric pull-up requiring laparotomy and pharyngogastric anastomosis in the neck. This is the three-stage oesophagectomy.
2. Tumours of the Thoracic Oesophagus and Cardia: They are usually adenocarcinomas. These tumours have a tendency to spread for long distances submucosally and the lymphatic flow is in the longitudinal direction. Two Choices
   1. Ivor Lewis operation: In this operation, abdomen is opened first, stomach is mobilised and the wound is closed. The patient is put in left lateral position, and right thoracotomy is done through 6th intercostal space. The growth is removed and oesophagogastric anastomosis is done inside the thorax, above the level of aortic arch. Hence, it is described as a two-stage Ivor Lewis approach.
      • However, a few surgeons do not advocate this surgery because of the following reasons:
        1. Higher incidence of pulmonary complications.
        2. Higher morbidity associated with anastomotic leak.
        3. Higher incidence of oesophagitis.
        4. Higher chances of local recurrence due to inability to resect long length of oesophagus. Hence, the alternate procedure (McKeown) is a better choice.
   2. McKeown’s three-stage en bloc oesophagectomy: En bloc resection is the best treatment with removal of all lymph nodes (abdominal and thoracic). Hence, three incisions are required:
      • Abdominal,
      • right postero-lateral thoracotomy through the fifth space, and
      • left cervical incision.
      • Local recurrence at the anastomosis is not a problem because of wide clearance (by obtaining a 10 cm margin of normal oesophagus above the tumour). Gastrointestinal continuity is obtained by gastric tube anastomosis to cervical oesophagus.
3. Carcinoma Lower Oesophagus and Cardia
   • They are adenocarcinomas.
   • Surgery is the best method of treatment and palliation.
   • En bloc resection is the best treatment with removal of all lymph nodes (abdominal and thoracic).
   • An alternative method is transhiatal oesophagectomy (THE) without thoracotomy. Figure 40.39 shows various types of oesophageal surgery done for carcinoma oesophagus.

Transhiatal Oesophagectomu Without Thoracotomy Orringer