16. Cancer of the oesophagus and the stomach

From greek.doctor

Oesophageal cancer

There are two major types of oesophageal cancer, adenocarcinoma and squamous cell carcinoma. Both type typically affect elderly men. Oesophageal adenocarcinoma evolves from the Barrett-mucosa and is the most common type of oesophageal cancer in the Western world. Its incidence is rising. It’s usually found in the lower part of the oesophagus.

Oesophageal SCC is more common in developing countries, and the most common type overall. It’s usually found in the middle and upper parts of the oesophagus. Its prognosis is worse than adenocarcinoma.

It’s usually asymptomatic in the early stages, and therefore is rarely discovered until the late stages. In the late stages it may present with non-specific symptoms like weight loss, dysphagia, and dyspepsia. At the time of presentation, most patients already have advanced cancer.

Etiology

Because adenocarcinoma evolves from GERD and Barrett oesophagus, the risk factors are the same as for GERD, especially smoking.

The risk factors for SCC are:

  • Alcohol consumption
  • Smoking
  • Diet low in fruits and vegetables
  • Exposure to nitrosamines in diet
  • Frequent consumption of very hot beverages, like the coffee at McDonalds.

Clinical features

Both types of oesophageal cancer have similar clinical features. It’s usually asymptomatic in the early stages, and therefore is rarely discovered until the late stages. In the late stages it may present with non-specific symptoms like dysphagia, odynophagia, cough, weight loss, and dyspepsia.

At the time of presentation most patients already have advanced cancer.

Diagnosis and evaluation

Upper endoscopy is the investigation of choice, as it allows for both visual diagnosis and biopsy. After the diagnosis is made, the most important is to determine the tumour’s resectability. Endoscopic ultrasound (EUS) is the preferred method for this, as it’s the most accurate technique for staging the tumour locally (T) and regionally (N). EUS can separate T1A and T1B stages.

CT thorax and abdomen is required for staging. Bronchoscopy is required if extension into the bronchial system is suspected.

Treatment

Proper evaluation and staging are essential to determine the resectability of the disease. Only around 1/3 of patients are operated on.

In the rare case where very early cancers are discovered, we may use minimally invasive methods like endoscopic resection or laser ablation. Locally advanced oesophageal cancer is treated with neoadjuvant chemoradiation, followed by surgery if the tumour is considered resectable on restaging, possibly followed by adjuvant chemotherapy.

Radiochemotherapy, targeted therapy, or immunotherapy may be used as palliative therapy for stage IV (advanced) disease. The placement of an oesophageal stent to keep the lumen open is an important palliative treatment option for oesophageal cancer, allowing for continued passage of food.

Surgery

Most patients present in a stage where radical surgery is required for cure. However, oesophageal resection is a large and complicated procedure, and patients often develop post-operative complications like nutritional problems, stenosis in the anastomosis, and slow passage of foodstuffs. After surgical resection of the oesophagus, either total or partial, the resected part of the oesophagus should be substituted with stomach (first choice) or colon. Because of the localisation of the oesophagus, oesophageal surgery may involve the neck, thorax, and/or the abdomen, making for a large and complicated surgery.

Surgery may be performed open, laparoscopically, or in combination.

Systemic therapy

Chemotherapy, most commonly the FLOT regimen, is commonly used in oesophageal cancer. In case of HER2 overexpression, trastuzumab (an anti-HER2 antibody) may be used as targeted therapy. In case of PD-L1 overexpression, pembrolizumab may be used as immunotherapy.

Radiotherapy

Radiotherapy is often combined with chemotherapy for oesophageal cancer.

Prognosis

The prognosis is very poor, with a 5-year survival of 15%. The 5-year survival of patients treated with curative surgery is around 30 – 40%. Squamous cell carcinoma has a worse prognosis than adenocarcinoma.

Gastric cancer

Gastric adenocarcinoma accounts for 95% of gastric cancers. It’s a cancer of elderly, mostly men, and it’s the fifth most common cancer worldwide. It is more common in Asian countries like Japan and Korea, as well as certain regions in Africa and South America.

It causes no or only nonspecific symptoms in the early stages. If diagnosed early, the prognosis is excellent, but at the time of diagnosis, 50-75% of cancers have already spread and are incurable, which leads to a poor prognosis overall.

The mortality of this cancer is higher in the countries with low prevalence because screening is not performed as often as in high-prevalence countries. Therefore, the cancer is often discovered too late.

Other types of gastric cancer are described at the end of the article.

Etiology

Plant-based diet is protective against gastric cancer.

Pathology and classifications

95% of cases of gastric cancer are adenocarcinomas. The carcinoma is usually located in the antrum, followed by corpus and fundus.

We distinguish “early” and “advanced” gastric cancer. Per definition, “early” gastric cancer infiltrates no deeper than the submucosa but even early cancer can give metastasis to the lymph nodes, while “advanced” cancers infiltrate the muscularis propria and deeper.

Metastatic spread

Gastric adenocarcinoma often spreads to skeleton, liver, lung, brain, and the peritoneum. The Virchow lymph node, the left supraclavicular lymph node, is the most common site of gastric cancer metastasis.

Diffuse type of gastric adenocarcinoma may metastasise to both ovaries (bilateral), forming a so-called Krukenberg tumour.

Clinical features

The stomach is large and spacious, meaning that the tumour may grow large before symptoms appear. Early symptoms of gastric cancer include dyspepsia and mild epigastric discomfort or pain. Later, symptoms like anorexia, early satiety, weight loss, anaemia, and nausea/vomiting.

Diagnosis and evaluation

Physical examination may reveal a tumour in the epigastrium, and an enlarged Virchow’s node (left supraclavicular lymph node). DRE may reveal positive Blumer sign. Faecal occult blood tests may be positive if the tumour is bleeding.

Upper endoscopy is the investigation of choice, as it allows for both visualisation and biopsy. After the diagnosis, CT thorax and abdomen are necessary for staging.

If peritoneal carcinosis is suspected but not visible on imaging, laparoscopy may be necessary to visualise the peritoneum and diagnose the carcinosis. Cytology may be obtained from the ascitic fluid. Molecular diagnosis is important to detect any overexpression of HER2, VEGF, or PD-L1 which is important in case of advanced cancer.

Treatment

Stages I – III are curable, with metastatic (stage IV) gastric cancer usually being incurable. Cancers located only in the mucosa or submucosa (“early” gastric cancer) may be treated endoscopically or with minimally invasive surgery.

Surgery

The standard curative surgical treatment for “advanced” gastric cancer patients is radical gastric resection with lymphadenectomy. For intestinal type gastric cancer, distal or subtotal gastric resection is performed. For diffuse type gastric cancer, total gastrectomy is necessary. Afterwards, the GI system must be reconstructed by Roux-en-Y, Billroth I, or Billroth II.

Surgery may be used palliatively as well, in cases where the tumour obstructs passage of foodstuffs, for example. A stent may be placed, the stomach may be resected, or bypass surgery may be employed.

Chemotherapy

Chemotherapy may be used neoadjuvant for downstaging (to allow for surgery with curative intent), as adjuvant therapy, and as palliative therapy. The most common regimens are FLOT and ECX.

Targeted and immunotherapy

Targeted therapy (anti-HER2 trastuzumab or anti-VEGF ramucirumab) may be used palliatively, as may anti-PD-L1 pembrolizumab.

Other gastric cancers

Gastrointestinal stroma tumor (GIST)

This type of tumor is the most common mesenchymal tumor from the interstitial Cajal-cells. It can occur anywhere in the GI-tract, but is most commonly found in the stomach, followed by the duodenum.

Gastric lymphomas

Lymphomas can arise in every tissue, but the stomach is the most common site of extranodal lymphoma. However, it’s still one of the rarest malignancies that you can have there. The lymphomas include:

  • MALT lymphoma
  • DLBCL – diffuse large B-cell lymphoma