Upper GI Tumors

 

• Oesophageal cancer

  Pathophysiology

  Either adenocarcinoma (⅔ of cases), occurring in the lower third of the oesophagus, or squamous cell carcinoma (⅓), which can occur at any level.

  Risk factors

  • Lifestyle and demographic: male, obesity, alcohol, high fat diet, smoking.
  • GORD and Barrett's oesophagus (intestinal metaplasia).
  • Achalasia, strictures.
  • H. pylori may reduce the risk.

  Signs and symptoms

  • Dysphagia and/or odynophagia. Difficulty with solids first, then liquids.
  • Weight loss.
  • Retrosternal pain.
  • If in the upper third: hoarse voice (recurrent laryngeal nerve palsy), cough during eating (may lead to aspiration pneumonia).

  Investigations

  • FBC may show microcytic anaemia.
  • Diagnosis: endoscopy and biopsy.
  • Staging: CT and endoscopic US. Consider PET to increase sensitivity for metastases.

  Management

  Curative:

  • ⅓ are potentially resectable, using open or laparoscopic oesophagectomy plus lymphadenectomy.
  • Neoadjuvant chemotherapy (cisplatin + 5FU) then remove tumour and anastomose remaining segment to stomach.
  • Localised squamous cell carcinoma can be treated with chemoradiation.

  Palliative, primarily to relieve dysphagia:

  • Dilatation, stenting, or laser treatment. No role for surgery in palliation.
  • Chemotherapy
  • Internal (brachytherapy) or external beam radiotherapy.
  • Argon plasma coagulation for bleeding.

  Prognosis

  • 15% 5 year survival.
  • Median survival: 12-18 months if treated curatively, 4 months if palliative only.

• Gastric cancer

  Pathophysiology

  90% are adenocarcinomas, divided into intestinal and diffuse types. Remaining 10% are lymphoma, leiomyosarcoma, and squamous cell.

  Intestinal (80%):

  • So called because they are well-differentiated tubular or glandular formations, like tumours elsewhere in the intestine.
  • Found in the cardia (30%), antrum (25%), or body (15%).

  Diffuse (10%):

  • Poorly-differentiated tumours which diffusely infiltrate the stomach wall.
  • May show signet ring cells on biopsy.
  • Poor prognosis.

  Classified as 'late' if it invades the muscularis propria (90% of cases).

  Risk factors

  • H. pylori
  • Demographic: ↑age, male.
  • Diet and lifestyle: nitrates and salt (pickling), smoking.

  Signs and symptoms

  Symptoms:

  • Weight loss (60%).
  • Epigastric pain (50%) is a late sign.
  • Nausea and anorexia (30%). Also vomiting, dyspepsia, and dysphagia (25%).
  • Less commonly, may present with upper GI bleeding (20%) or perforation.
  • Symptoms of anaemia e.g. SOB, fatigue.

  Signs:

  • Epigastric mass.
  • Hepatomegaly, jaundice, and/or ascites.
  • Virchow's node.
  • Acanthosis nigricans.

  Investigations

  • Bloods: FBC (↓Hb) and LFT (spread).
  • Diagnosis: gastroscopy and biopsy.
  • Staging: CT chest-abdo-pelvis and staging laparoscopy. If no mets found, endoscopic US +/- PET to increase sensitivity.

  Management

  Surgery:

  • Curative: gastrectomy – total if proximal and subtotal if antral – plus lymphadenectomy.
  • Palliative: subtotal gastrectomy, especially for obstructing tumour.

  Chemotherapy:

  • Perioperative (pre and post) chemo with {epirubicin + cisplatin + 5FU} if localised, or adjuvant chemoradiation if advanced.
  • Also used for palliative care.
  • Trastuzumab if HER2 +ve. Improves survival.

  Other palliative measures:

  • Endoscopic pyloric stent – a plastic tube through the tumour – can relieve obstruction.
  • PPIs for bleeding, ulcerating tumours.
  • Argon plasma coagulation for bleeding.

  Complications and prognosis

  Spread:

  • Diffuse cancer spreads within stomach wall, causing linitis plastica (aka leather bottle stomach), which can't properly expand.
  • Outside of stomach: local (pancreas, liver, spleen), lymphatic, transcoelomic, haematogenous (commonly to lung).

  5 year survival: 15%.

• Pancreatic cancer

  This discusses exocrine tumours. See other upper GI tumours for discussion of endocrine tumours.

  Pathophysiology

  • Usually ductal adenocarcinoma of the pancreatic head (80%). Remainder are in the tail or body.
  • Periampullary tumours are those that arise within 2 cm of the ampulla of Vater in the duodenum. This includes some pancreatic head cancers, but also (non-pancreatic) ampullary carcinoma.

  Signs and symptoms

  Symptoms:

  • Weight loss, anorexia.
  • Head tumour: painless obstructive jaundice.
  • Body or tail tumour: epigastric pain that radiates to back, relieved on leaning forward.

  Signs:

  • Palpable gallbladder, liver, and/or spleen. Courvoisier's law states that a palpable gallbladder with jaundice is rarely due to gallstones, as in chronic gallstone disease the gallbladder is fibrosed and can't expand.
  • Ascites
  • Trousseau's sign (of malignancy): hypercoagulability and migratory thrombophlebitis. May also be seen in gastric or lung cancer.

  Risk factors

  • Lifestyle: smoking, obesity, alcohol, red/processed meat.
  • Medical: diabetes, chronic pancreatitis, non-O blood group, H. pylori.
  • Family history.

  Investigations

  • Abdo US has 75% sensitivity.
  • Follow up with CT, which usually confirms the diagnosis. Will also show if resectable i.e. no spread to liver, nodes, or vessels. ERCP, MRCP, or FDG-PET if CT unclear.
  • Endoscopic US (EUS) to guide needle biopsy for histological confirmation, or if diagnosis remains uncertain.
  • Staging laparoscopy may be used if resectability is unclear.
  • ↑CA19-9: 80% sensitive, 90% specific. Useful for staging and assessing treatment response.

  Management

  • Pancreaticoduodenectomy (Whipple's procedure) if resectable (20%). 5% surgical mortality.
  • Biliary stent insertion by ERCP if unresectable. Reduces jaundice and itch.
  • Chemotherapy if unresectable or post-surgery: FOLFIRINOX if good performance status, gemcitabine (± nab-paclitaxel or capecitabine) otherwise.
  • Medical: analgesia, pancreatic enzyme supplementation, domperidone or metoclopramide for nausea and vomiting.

  Prognosis

  • 5 year survival 3%. 20% if resectable.
  • Periampullary cancers, and especially ampullary carcinoma, have a better prognosis due to earlier biliary obstruction and hence earlier presentation.

• Other upper GI tumours

  Gastrointestinal stromal tumours (GISTs)

  • Arise from interstitial cells of Cajal, the GI pacemaker cells.
  • A type of mesenchymal tumour. Other mesenchymal tumours include leiomyomas, leiomyosarcomas, and neurofibromas.
  • Usually in the stomach, and usually (75%) benign.
  • May be asymptomatic, or present with abdo pain, GI bleed, or obstruction.
  • Imatinib or sunitinib can be used for c-Kit positive tumours.

  Small bowel tumours

  Types:

  • Adenocarcinoma from adenomatous polyps.
  • Carcinoid tumours.
  • Lymphoma

  Carcinoid syndrome

  • Neuroendocrine tumours which secrete serotonin and kinins, arising in midgut (commonest) or lung.
  • Signs and symptoms: diarrhoea, flushing, wheeze.
  • May metastasize to heart valves (carcinoid heart disease), causing fibrosis of right-sided valves.
  • Investigations: ↑5-HIAA in 24h urine, somatostatin receptor scintigraphy (SRS), CT.
  • Surgical resection if localised, or somatostatin analogues and interferon alpha if metastatic.

  Pancreatic neuroendocrine tumours (islet cell tumours)

  • Includes insulinomas, gastrinomas (Zollinger-Ellison syndrome), glucagonomas, VIPomas, and somatostationomas.
  • Presentation depends on hormone secreted.
  • May be part of MEN 1.
  • Insulinomas are often benign and have a good prognosis. The others are often malignant and have a poorer prognosis, though better than pancreatic exocrine tumours.

  Zollinger-Ellison syndrome

  • Gastrinoma in pancreas (commoner), duodenum, or stomach. 60% are malignant.
  • Presentation: refractory ulceration, most commonly affecting the (whole) duodenum, as well as diarrhoea and abdominal pain.
  • Investigations: ↑gastrin (fasting), gastric acid secretion studies, secretin stimulation test, SRS, CT.
  • Management: PPIs, and surgery if tumour can be found. As many are very small intra-pancreatic tumours, intraoperative US may be needed to localize them.