Editing Oesophageal cancer (section)

== '''Pathophysiology''' ==

* Think of it as two separate     disease processes, with separate risk factors
** However, controversial      whether this actually influences treatment approach
** SCC tends to respond more      favourably to chemoradiotherapy
* Check biomarkers:
** dMMR - checkpoint modulator
** PD-L1 - checkpoint modulator
** HER2 for gastric/GOJ      adenocarcinoma - trastuzumab

=== '''Adenocarcinoma     (60%)''' ===

** Risk factors:
*** Modifiable:
**** Smoking
**** Obesity
**** NOT alcohol
*** Non-modifiable:
**** GORD/Barrett's/oesophageal        acid exposure - duration and frequency of symptoms is correlated with        risk
**** There are familial forms        of Barrett's that increase the risk
**** Caucasian men
** Generally found at GOJ and      a/w Barrett's
** Increasing prevalence in      developed countries
** Adenocarcinomas usually      metastasise intra-abdominally

=== '''SCC (40%)''' ===

** Risk factors:
*** Modifiable
**** Smoking and alcohol are        the main risk factors (~90% of cases)
***** Synergistic effect on         risk
**** Dietary factors -        N-nitroso, hot drinks
**** Caustic ingestion
*** Non-modifiable
**** HPV (probably only a small        proportion of cancers)
**** Plummer-Vinson syndrome
**** Achalasia
**** Upper aerodigestive tract        SCC
**** Tylosis
**** Fanconi anaemia
**** 4x more prevalent in men
** Pathophysiology
*** Premalignant lesion is       squamous dysplasia (a.k.a. squamous intra-epithelial neoplasia). Over a       13.5 year follow-up, SCC developed in 24%, 50% and 74% of patients with       mild, moderate and severe dysplasia at baseline, compared to 8% of       patients with normal index histology.
*** Squamous dysplasia can       regress and relapse spontaneously. Can be present anywhere in the       oesophagus. Chromoendoscopy with Lugol's iodine or NBI helps to identify       it.
*** Squamous dysplasia should       be treated with EMR/ESD depending on size


* Generally proximal- or     mid-oesophagus - at or higher than carina
* Decreasing prevalence in     developed countries
* Usually metastasises     intra-thoracic, and metastasises earlier than adenocarcinoma
* Worse prognosis

=== '''Rare     malignant tumours''' ===

** '''Small cell      carcinoma (0.6%)'''
*** Aggressive phenotype,       similar to other poorly-differentiated neuroendocrine cancers
*** Typically present with       lymph node involvement already
*** Overall prognosis poor but       long-term survival is possible with curative resections
** '''Primary      melanoma of the oesophagus (0.1%)'''
*** Generally late stage at       presentation, with poor prognosis
** '''Leiomyosarcoma'''
*** Far less common than       leiomyoma
*** Often erode through mucosa,       appearing as an ulcerated or exophytic mass
*** EUS - irregular borders and       more heterogenous than would be seen with leiomyoma
*** Oesophagectomy with radical       lymphadenectomy is treatment of choice, although prognosis is poor
** '''GIST'''
*** Similar appearance to       leiomyoma, differentiated by CD117 (c-kit) and CD34 stain positivity.       Also tend to be larger than leiomyomas, with uptake of IV contrast on CT       and significant PET avidity.
*** Can be enucleated provided       negative margins can be obtained; if not, formal oesophagectomy will be       required
*** Consider imatinib for any       GIST >3cm or with high-risk factors, or as neoadjuvant therapy for       locally advanced tumours
*** Lymph node metastasis is       unusual
*** Worse prognosis than       gastric GIST