What are the types of aero digestive tract fistulas?

Tracheo-oesophageal fistula (TOF)

Broncho- oesophageal fistula (BOF)

Oesophageal-lung parenchyma fistulas (rare)

What are the causes of these fistulas?

• These fistula’s develops either because of direct tumor invasion and subsequent perforation or after radiation, laser therapy, chemotherapy or pre-existing stents (primarily, oesophageal stents), or a combination of these.

• Approximately 77% of MTOF are related to oesophageal cancer, whereas approximately 16% originate from a primary lung neoplasm.

• Other tumours like malignant mediastinal nodal disease, thyroid, laryngeal cancer etc causes MTOF rarely

How common is it?

It develops in approximately 5%–15% of patients with an oesophageal malignancy and in less than 1% of those with bronchogenic carcinoma

What are the symptoms?

Intractable cough and repeated aspirations.

Autopsy data indicate a higher incidence of fistulas, thus suggesting that fistulas are more common in patients than is usually diagnosed.  A history of repeated coughing associated with eating, drinking, or both, with an increase in dysphagia and dyspnea are highly suggestive of a fistula. Endoscopic findings are sometimes inadequate in demonstrating a fistula, in which case a water contrast swallow is required.

Lung abscess is the most frequent and severe complication of oesophageal-lung parenchyma fistulas. In this particular type of aero digestive fistula, stent placement may worsen the infectious problem by impairing natural drainage of the abscess.

In one study, lung abscesses decreased in size, but persisted even after stent placement. Concomitant abscess drainage procedures should thus be considered. Thus, oesophageal stent remains the accepted treatment for oesophageal-lung parenchyma fistulas (with percutaneous drainage of the abscess)

What is the prognosis?

Once a fistula (stage T4) develops, the tumour is incurable. The treatment is palliative to alleviate symptoms. Treatment should be begun immediately after the diagnosis is confirmed since the usual cause of death in these patients is pulmonary sepsis resulting from chronic aspiration through the fistula. In two, large series reports (4, 5), mean patient survival was reported to be 3.1-3.4 months. The usual causes of death are: massive bleeding, pneumonia or malnutrition

What are the treatment options?

Therapy is mainly directed to palliate symptoms and maintain quality of life.

• Unfortunately, at the time of diagnosis, the patient’s performance and disease status usually precludes aggressive palliative surgical therapy (oesophageal bypass using a gastric bypass and cardiostomy)

• Radiation therapy and chemotherapy are generally contraindicated due to the concern regarding fistula enlargement caused by tumor necrosis.

• Oesophageal or tracheobronchial stenting or both is the treatment of choice.

• Gastrostomy: Stenting however achieves better palliation of respiratory symptoms with a better quality of life.

Discuss selection of stent?

Several kinds of covered oesophageal stents are available (i.e., Ultraflex stent, Wallstent, and Z stent). However, there are no randomized or controlled trials to compare the outcomes of any of these stents when used to treat malignant aero digestive fistulas

Discuss the stenting area?

The selection guide for determining the stenting area could be summarized as follows:

• oesophageal stent placement if a patient has a stricture in the oesophagus,

but with no or only mild airway stricture since an oesophageal stent can successfully treat both oesophageal stricture and a fistula;

• airway stent placement if a patient has no or only mild stricture in the oesophagus, or has moderate to severe stricture in the airway, since an oesophageal stent migrates well when oesophageal stricture is absent or mild, and an airway stent can treat an airway stricture; or
• both the airway and oesophageal stent placement when a patient has moderate to severe stricture involving both the oesophagus and the airway, since both the airway and oesophageal stents are necessary to treat a stricture involving both the oesophagus and the airway.
• In case of a high (fistula at 18-20cm from incisor) tracheo-oesophageal fistula –oesophageal stent may be undesirable and a tracheal stent is the better option.

NB: Airway stent is preferred in malignant fistula developing after Ivor Lewis

Oesophagectomy (the replaced stomach or colon shows a large lumen compared

with the lumen of the original oesophagus). The larger lumen makes oesophageal stent migration (and hence uncovering fistula) easier.

Discuss double stenting i.e. both oesophageal and Tracheobronchial stent insertion?

Double stenting appear to provide more benefits than either oesophageal or respiratory stents alone in terms of palliation and safety. Double stenting is definitely indicated when fistula occlusion is not achieved by the oesophageal or airway stent alone. In cases of double stenting, airway stent should be placed first in order to avoid tracheal or bronchial compression secondary to the oesophageal stent.

Mechanical friction between the oesophageal and airway stents may cause pressure necrosis of the interposed tissue between the two stents, thereby possibly resulting in a fatal haemorrhage. Thus, parallel stenting should only be performed after thoroughly reviewing a patient’s clinical indications.

Discuss the success of oesophageal stenting?

• Oesophageal stenting is technically feasible in the majority.

• Oesophageal stent completely seals off the fistula in 60-100% of cases. Incomplete closure of the fistula caused by spillage of material through a gap between the proximal stent margin and the oesophageal wall (‘funnel phenomenon’). This is difficult to manage despite the insertion of additional stents or glue injection to seal the gap. An additional airway stent is usually required. Thus, a contrast swallow is obtained immediately after stent insertion to confirm the sealing of the fistula and subsequently allow a patient to eat a soft diet. If there is persistent leakage through the fistula, resulting from an incomplete stent expansion, a follow-up contrast swallow should be obtained 2-3 days after stent placement in order to confirm stent expansion before food intake is resumed.

• The fistulas may reopen/recur in 0-20% of cases. The reported causes of reopening following stent placement were stent occlusion (caused by tumor overgrowth or in growth, food impaction, or granulation tissue formation), stent migration, and stent covering disruption.

Does stenting have a survival advantage?

A recent study (3) compared treatment of MTEF in three groups:  oesophageal stent group, gastrostomy group and control group (refused both stenting and gastrostomy).

There was no statistical difference in survival time (Average survival time for stent group was 93 days with a range of 44-165 days, gastrostomy group- 62 days, range 41-111 days and control group survival time was 66 days- range 20-119 days).

In two, large series reports (4, 5), mean patient survival was reported to be 3.1-3.4 months. In one of these reports (4), the survival benefit was significant in patients in the stenting group (3.4 months) compared with the gastrostomy group (1.1 months), and the supportive management group (1.3 months).

NB: It is very important to carefully evaluate the airway stenosis with CT scans or

bronchoscopy prior to oesophageal stent placement, since it is possible to develop tracheal compression caused by expanding oesophageal stents. Further, for airway

stenting, reconstructed CT images are very useful for measuring the distance between the fistula and a carina or vocal cord, in the determination optimal stent length.

References:

1.Rodriguez AN, Diaz-Jimenez JP. Malignant respiratory-digestive fistulas. Curr Opin Pulm Med. 2010 Jul;16(4):329-33.

2. Shin JH et al. Interventional management of esophagorespiratory fistula. Korean J Radiol. 2010 Mar-Apr; 11(2):133-40.

3. Hu Y et al. Comparative study of different treatments for malignant tracheoesophageal/bronchoesophageal fistulae. Dis Esophagus. 2009;22(6):526-31.

4. Balazs A, Kupcsulik PK, Galambos Z. Esophagorespiratory fistulas of tumorous origin. Non-operative management of 264 cases in a 20-year period. Eur J Cardiothorac Surg 2008;34:1103-1107

5. Shin JH, Song HY, Ko GY, Lim JO, Yoon HK, Sung KB. Esophagorespiratory fistula: long-term results of palliative treatment with covered expandable metallic stents in 61 patients. Radiology 2004;232:252-259

Oesophageal carcinoma

The majority of oesophageal cancers are squamous cell (SCC) or adenocarcinoma (AC).

Clinical manifestations

• Dysphagia- usually occurs once the oesophageal lumen diameter is less than 13 mm.
• Weight loss
• Tracheobronchial fistulas-The fistulas are caused by direct invasion through the oesophageal wall and into the main stem bronchus. Life expectancy is less than four weeks following the development of this complication.

Investigations

• OGD and biopsies (at least 8 biopsy samples)- A classification of oesophagogastric tumours, proposed by Siewert and Stein is recommended, as it is uniform, allows data comparison from different centers, and is important for the stratification of patients in prospective studies.
  • Type I tumour-AC of the distal oesophagus, the centre of the tumour lying 1–5 cm above the anatomical cardia.
  • Type II tumour- AC of the cardia with its centre situated between 1 cm above and 2 cm below the anatomical cardia;
  • Type III tumour is a gastric carcinoma with its centre between 2 and 5 cm below the anatomical cardia.
• Staging CT scan of chest, abdomen and pelvis for distant metastasis
• EUS for loco regional staging (T, N staging)
• Laparoscopy may be needed where there is suspicion of peritoneal spread on CT or EUS such as in the presence of small volume ascites.

TNM staging

• Tumours of lower thoracic oesophagus- M1a- coeliac nodes involvement, M1b- Other distant metastasis
• Tumours of the mid thoracic oesophagus: M1a- not applicable. M1b- Non regional lymph nodes and/or other distant metastasis
• Tumours of the upper thoracic oesophagus: M1a- Metastasis in cervical nodes M1b- Other distant metastasis.

Management of resectable tumours

Who are surgical candidates?

• Radical surgery is recommended for patients with localised (T1, T2) tumours that are sufficiently fit to tolerate the procedure.
• Combination therapy should be considered for T2 tumours. Preoperative chemotherapy (2 cycles of cisplatin and 5FU) for all patients with operable oesophageal cancer other than those with unequivocally T1 tumours provides a gain in median and two-year survival compared to surgery alone. This is thus the standard of care in the UK based upon the MRC trials. There is no evidence to support the use of preoperative radiotherapy in oesophageal cancer.
• Patients with advanced oesophageal cancer (T3N1) should be considered for RCTs to assess the role of novel multimodality therapies in combination with surgery.

What is the type of surgery needed?

Patients with either AC or SCC involving the middle or lower third of the oesophagus generally require total oesophagectomy because of the risk of submucosal skip lesions. The most popular methods used are the transhiatal and transthoracic (Ivor-Lewis) approaches. Gastric interposition is most commonly used as a conduit for reconstruction following oesophagectomy.
A radical two-field (abdominal and thoracic) lymph node dissection is also undertaken. Japanese do a three field (including neck) lymph node dissection.

What are the risks of surgery?

Clinical anastomotic leakage should not exceed 5%. Curative (R0) resection rates should exceed 30%. Overall hospital mortality for oesophageal resection should be less than 10%.

What is the prognosis?

Five year survival rate is over 80% when tumours are confined to the mucosa and between 50% and 80% when the submucosa is involved.

What is the role of adjuvant chemotherapy?

There is no evidence for a role of adjuvant chemotherapy in oesophageal cancer. However, for patients with completely resected node-positive disease who have not received neoadjuvant therapy, postoperative adjuvant chemotherapy should be considered, although whether chemotherapy alone or chemoradiotherapy should be used is unclear.

Is there any role of chemo-radiation?

• Chemoradiation is the definitive treatment of choice for localised squamous cell carcinoma of the proximal oesophagus.
• Carcinoma of the cervical esophagus (6-8 cms long from cricopharyngeus till thoracic inlet) presents a unique management situation. Radiation combined with chemotherapy is generally preferred over surgery since long-term survival appears to be similar, and major morbidity is avoided in most.

What is the role of local treatments?

All submucosal tumors have a substantial risk of lymph node metastases. Local lymph node invasion occurs early and quickly because the lymphatics in the oesophagus are located in the lamina propria, in contrast to the rest of the gastrointestinal tract, in which they are located in the submucosa. Hence, local treatments like Endoscopic mucosal resection (EMR) and photodynamic therapy (PDT) may be considered in selected patients (especially poor surgical risk patients) as potentially curative options for superficial oesophageal cancer, confined to the mucosa.

Who is fit for surgery?

The previous medical history and concurrent morbidity remain the strongest predictors regarding fitness for surgery. Pre-existing ischaemic heart disease, poorly controlled hypertension, and pulmonary dysfunction are all associated with increased operative morbidity. The American Society of Anaesthesiologists (ASA) classification of physical status is well recognised. Perioperative risk increases with increasing ASA score. Only those patients with an ASA score of 3 or less should be considered for surgery.

How do you follow up these patients post treatment?

There is little consensus for the mode, duration, or intensity of follow up in patients with malignant disease. There is no evidence that intensive follow up improves the speed of detection of recurrent disease in oesophageal or gastric cancers. However, majority of patients prefer regular follow up.

Management of unresectable oesophageal cancer

What is an unresectable tumour?

• Any T4 lesion
• Any M lesion with the exception of coeliac nodes for distal adenocarcinomas.

The current staging system for oesophageal cancer is based largely on retrospective data from the Japanese Committee for Registration of Oesophageal Carcinoma. It is most applicable to patients with SCC of the upper- and middle-thirds of the oesophagus, as opposed to the increasingly common distal oesophageal and GO junction adenocarcinomas. In particular, the classification of involved abdominal lymph nodes as M1 disease has been criticized. The presence of positive abdominal lymph nodes does not appear to carry as grave a prognosis as metastases to distant organs. Patients with regional and/or coeliac axis lymphadenopathy should not necessarily be considered to have unresectable disease due to metastases. Complete resection of the primary tumor and appropriate lymphadenectomy should be attempted when possible.

What are the Palliative options for unresectable disease?

1. First line treatment-

Combined chemoradiotherapy should be first line of treatment as this offer a small but real chance of sustained disease control and long term survival. Approximately 60% of patients would be dysphagia free till death. However, the time to onset of improvement of dysphagia is slow. In a study, median time to improvement in symptoms was two months after radiotherapy, variable but prolonged after chemotherapy, and immediate after stent insertion.

Who is fit for chemotherapy?

Fitness for chemotherapy is generally assessed by using The World Health Organisation performance scale. It has categories from 0 to 4. 
0 – fully active patient.
1 – cannot carry out heavy physical work, but can do anything else.
2 – up and about more than half the day; can look after himself, but not well enough to work.
3 – in bed or sitting in a chair for more than half the day; need some help in looking after him
4 – in bed or a chair all the time and need a lot of looking after
Good performance status is 0 or 1. Poor performance status is 2-4.
Generally patients are considered fit for chemotherapy with good performance status (PS0, PS1). Good PS2 (leaning towards PS1) are also generally considered fit for chemotherapy

2. Endoscopic palliation may be appropriate for palliation of dysphagia in patients awaiting definitive treatment or patients unfit for chemoradiotherapy.
   1. Covered expandable metal stents is the treatment of choice. They are also the treatment of choice for malignant tracheoesophageal fistulation or following oesophageal perforation sustained during dilatation of a malignant stricture. The tumour should be more than 2 cm from the cricopharyngeus for stenting.
   2. Dilatation alone should be reserved for patients who are considered to have an extremely short life span (four weeks or less) and unable to swallow saliva, or as a very short term measure to relieve dysphagia while more definitive treatment is planned. Most malignant strictures can be safely dilated to 16 or 17 mm in several sessions. However, repeat dilatation is usually required every two to four weeks.
   3. Laser or APC- consider it in short segment cardia tumours- where a stent would have a high risk of migration/displacement. APC/Laser could also be used for tumour overgrowth at the end of stents. Treatments are performed every other day and are usually completed in three to four sessions (one week). Relief may last for one to several months and treatments may have to be repeated. Further, Laser therapy or judicious and careful use of oesophageal dilatation is widely held to be the best form of palliative treatment for cervical oesophageal tumours within 2 cm of the upper oesophageal sphincter.

Survival

Reported five-year survival rates for stages I to IV disease are 60, 31, 20, and 4 percent, respectively.

Normal oesophageal structure:

1. Mucosa-
   1. Nonkeratinized stratified squamous epithelium
   2. Lamina propria- loose network of connective tissue in which blood vessels, scattered lymphocytes,macrophages and plasma cells
   3. Muscularis mucosae- thin layer of circular muscle between lamina propria and submucosa
2. Submucosa- dense network of connective tissue containing blood vessels, lymphatic channels, Meissner’s plexus and oesophageal glands
3. Muscularis propria- inner circular layer, Auerbach’s myenteric plexus and outer circular layer
4. Adventitia-

Ref:

1. British Society of Gastroenterology Guidelines for the management of Oesophageal and gastric cancer
2. http://cancerweb.ncl.ac.uk/cancernet/100089.html

Self assessment

1. Alcohol is an important risk factor for oesophageal adenocarcinoma
2. Oesophageal carcinoma tend to metastasis early
3. Oesophageal lymphatics are situated in the mucosa
4. T4 tumours are unresectable
5. Performance stage 3 patients are generally fit for chemotherapy
6. Siewert and Stein type III tumour is an oesophageal adenocarcinoma
7. Achalasia increases the risk of oesophageal adenocarcinoma
8. M1a (coeliac node positive) for distal oesophgeal carcinoma is unresectable
9. Neoadjuvant chemotherapy should be considered for T1 tumours
10. ASA class III patients can be offered oesophageal surgery.

Answers :
F T T T F F F F F T