GI Neoplasms

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Liver

Hepatocellular Carcinoma

  • Pathogenesis:
    • Malignancy of hepatocytes
    • 75% of primary liver cancers
  • Epidemiology & Risk Factors:
    • EtOH (chronic use)
    • Chronic HBV or HCV infection
    • Cirrhosis (5% lifetime incidence)
    • Aflatoxin exposure (mold found on nuts and grains)
    • Male (questionable whether this is an independent risk factor)
    • FHx
  • Presentation:
    • "Alarm" triad: weight loss, anorexia, increased fatigue
    • RUQ pain, possibly radiating to back
    • Jaundice
  • Examination:
    • Ascites
    • Possible enlarged or nodular liver
  • Investigations:
    • ↑α-fetoprotein (screen also)
    • Abdo CT/ultrasound (screen also, Sn = 0.70, no mortality data)
    • Bx is definitive (fine needle aspiration or CT-guided core Bx)
  • Complications:
    • Typical Complications of end-stage liver disease (jaundice, coagulopathies, encephalopathy etc.)
  • Treatment:
    • Localized, resectable: hepatectomy
    • Localized, unresectable:
      • Radiofrequency ablation (probe-guided)
      • Percutaneous ethanol injection
      • Ultrasound-guided cryosurgery
      • Hepatic artery infusion of chemotherapeutic agents
      • Hepatic artery chemoembolization (Nr, healthy hepatocytes still get perfusion from portal vein)
      • Transplant is definitive, but survival rates were poor (3y survival was 20-30% because of recurrence); current guidelines suggest that transplants be considered only in patients with
        1. No vascular invasion
        2. A single lesion <5cm in diameter OR
        3. Three or fewer lesions, the largest of which is <3cm in diameter
      • Advanced: systemic chemotherapy

Cholangiocarcinoma

  • Pathogenesis:
    • Adenocarcinoma of the bile duct epithelia
  • Epidemiology & Risk Factors:
    • 10-20% of all primary liver cancers
    • Cholelithiasis
    • Cholecystitis
    • UC
    • Parasitic infection: Clonorchis sinensis (most common worldwide cause), Opisthorchis viverrini
    • Primary sclerosing cholangitis
  • Presentation:
    • As HCC
    • RUQ pain (47%)
    • Obstructive jaundice (90%)
  • Examination:
    • As HCC
  • Investigations:
    • Similar to HCC, but will give a cholestatic picture rather than a hepatocellular one
  • Complications:
    • Often asymptomatic until very advanced, and usually unresectable d/t the anatomic difficulty in reaching the tumor; thus prognosis is poor
    • 5y survival < 10%
  • Treatment & Prognosis:
    • Bile duct bypass (palliative)
    • Chemo and radiotherapy usually ineffective
    • Surgical drainage for infected ducts

Angiosarcoma

  • Rare, endothelial in origin
  • Risk factor is exposure to vinyl chloride
  • Aggressive, resistant to treatment, most do not survive past 6mo


Hepatoblastoma

  • Rare, occurs in children usually < 4
  • Usually resectable, and survival is > 90% if caught early


Liver Cancer Screening

  • screen high risk patients, despite a lack of proven value
  • part of management of pts. with end stage liver disease
  • generally offered to those infected with hep B and sometimes C, and those who have cirrhosis, regardless of etiology
    • "In the absence of documented benefit of mass screening, the committee makes no recommendations for or against screening for HCC in HBsAg-positive patients, nor for patients with chronic hepatitis C. Screening may be justified in high risk cases (presence of cirrhosis, long duration of infection, HBV/HCV co-infection, past curative resection for HCC, family history of HCC [HBV only])." -Public Health Agency of Canada http://www.phac-aspc.gc.ca/publicat/casl-acef/vhe_e.html


Screening Tools

  1. Serum AFP
    • not specific for HCC (can be elevated in acute hep, cirrhosis)
    • studies suggest it should perhaps be used for surveillance, not Dx
    • no guidelines as to when a rise in AFP with normal US should lead to further Ix
    • sensitivity around 50%
  2. US
    • sensitivity around 70%
  3. Surveillance interval
    • vary from 3 to 12 mo.
    • favour 6 mo. based on study from China where tumour doubling time in asymptomatic HCC was less than 5 cm; most rapidly diving tumour took 6 months to grow from 1 cm to 3 cm (undetectable _ detectable)

Utility

  • 80% of those who develop HCC have underlying cirrhosis
  • HPC is well known complication of chronic Hep B infection
  • no RCTs to show screening reduces mortality
  • HPC is usually multifocal and often in a cirrhotic liver _ may not be respectable

Risks/Costs

  • very costly per year of life saved

Benefits

  • some studies show that tumours detected via screening are smaller and perhaps more likely to successfully undergo curative therapy _ disease more treatable if caught early
  • 2 large North American studies of screening in hepatitis B carriers _ one suggests that screening is very effective at finding curable tumours, whereas the other suggests otherwise.

study in Japan showed overall five-year survival rate was 51% for asymptomatic tumours compared to 21% for symptomatic HCC

References

  1. Yang B. Zhang B. Xu Y. Wang W. Shen Y. Zhang A. Xu Z. (1997) Prospective study of early detection for primary liver cancer. Journal of Cancer Research & Clinical Oncology 123(6):357-60.
    • Abstract: PURPOSE: To determine whether repeated screening can lead to early detection of primary liver cancer (PLC) and in turn to an improved clinical result. METHODS: In this randomized controlled study, Shanghai urban residents aged 35-55 years and with serum evidence of HBV infection or chronic liver disease were eligible for recruitment. Using cluster sampling, these subjects were allocated into two groups-the screening group and the control group: there were 8109 subjects in the screening group and 9711 in the control group. Subjects in the screening group were tested with serum AFP and real-time ultrasound every 6 months. One to four rounds of screening were completed. Liver cancer was treated according to stage at diagnosis. RESULTS: All subjects enrolled were followed up and classed at the end-point as alive without liver cancer, alive with liver cancer, dead from liver cancer, or dead from another cause. The mean follow-up was 1.2 years; total follow-up was 12,038 person-years in the screening group and 9,573 person-years in the control group. We detected 38 patients with PLC in the screening group and 18 patients with PLC in the control group. In the patients in the screening group 76.8% of patients were at a subclinical stage, and 70.6% of them underwent resection, the 1- and 2-year survival rates being 88.1% and 77.5%, respectively. However, in the control group, none of the patients was at a subclinical stage when diagnosed, none of them underwent resection, and none of them survived over 1 year. The lead time was estimated at 0.45 years. The cost of detecting PLC at an early stage was RMB 12,600 (US$1,500). CONCLUSION: The study proved that screening the high-risk population for PLC with a serum AFP test and real-time ultrasound Examination can detect patients in the early stages, increase the resection rate and prolong the survival time. It is therefore recommended that screening for PLC be advocated in any high-risk area.
  2. Sherman M. Peltekian KM. Lee C. (1995) Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology 22(2):432-8..
    • Abstract: OBJECTIVE: To prospectively determine the prevalence and annual incidence of hepatocellular carcinoma in hepatitis B carriers in a heterogeneous urban North American population and to assess the diagnostic accuracy of tests used for screening for this cancer. DESIGN: Prospective cohort study of 1,069 chronic carriers of hepatitis B virus using screening with alpha-fetoprotein alone or in combination with ultrasonography every 6 months. RESULTS: The mean age of the cohort was 39 +/- 12 years (+/- SD), 65% were men, 71% were Asians. At the first screening visit, serum alpha-fetoprotein was > or = 20 micrograms/L in 4%. In those subjects who were also screened by ultrasonography during the first visit, 9% were found to have focal lesions. Only 3 subjects were found to have hepatocellular carcinoma at the first screening, giving a prevalence of 281/100,000 chronic carriers of hepatitis B virus. The cohort was followed for 2,340 person-years (mean, 26 months follow-up, with a range from 6 to 60 months). During this period, 11 more subjects, 10 men and 1 woman, were diagnosed to have hepatocellular carcinoma (annual incidence, 470/100,000). In men only, the annual incidence was 657/100,000. During the study, 5 subjects died from hepatocellular carcinoma (annual mortality rate, 214/100,000). Sensitivity and specificity of serum alpha-fetoprotein > 20 micrograms/L were 64.3% and 91.4%, respectively. For ultrasonography, sensitivity was 78.8% and specificity 93.8%. CONCLUSIONS: These data suggest that the incidence and prevalence of hepatocellular carcinoma in hepatitis B carriers in our area, an urban North American setting, are as high as in countries where hepatitis B is endemic. Current screening tests have significant false-positive and false-negative rates raising questions about the cost-benefit of screening for hepatocellular carcinoma in our study population.
  3. Morris Sherman, MD. Screening for Hepatocellular Carcinoma http://www.hepnet.com/boca/sherman.html
    • Learning Objectives:
      • To develop a clear rational strategy for using the various treatment modalities for patients with hepatocellular carcinoma
      • To understand the role of screening in the management of hepatocellular carcinoma
    • Abstract: Hepatocellular carcinoma is a frequent complication of cirrhosis from many etiologies. However, the most commonly HCC occurs in hepatitis B carriers, or in hepatitis C carriers who have cirrhosis. Since the development of HCC is unpredictable, methods have been developed to try to identify HCC's early, while there is still a chance of cure. Screening and surveillance programs have been developed using serum alpha-fetoprotein (AFP) levels, and ultrasonography at regular intervals.


Colon

Colorectal Carcinoma

  • Pathogenesis:
  • Epidemiology & Risk Factors:
    • Age > 50
    • High fat diet
    • Central obesity
    • Cigarette smoking(polyps)
  • Presentation:
  • Examination:
  • Investigations:
    • FOB test recommended q2y over the age of 50 (qy for high risk)
    • FOB qy + sigmoidoscopy q5y: Sn = 0.76
  • Complications:
  • Treatment & Prognosis:


Esophagus

  • Cancer of the esophagus may develop anywhere along the length of the esophagus.
  • Pathogenesis: 2 types
    1. Squamous Cell Carcinoma (90% worldwide; 40% Canada of all Esophageal Neoplasms)
      • starts in the squamous cells that line the esophagus, majority lower thir
    2. Adenocarcinoma (60% of Esoph. Np. cases in North America)
      • Glandular cells of the lower third of the esophagus or in cells that have been damaged by acid backing up from the stomach
  • Epidemiology & Risk Factors:
    • age > 60
    • male gender
    • smoking - particularly if combined with heavy alcohol consumption
    • heavy alcohol consumption - particularly if combined with smoking :)
    • damage to the lining of the esophagus - such as the damage caused by many years of chronic indigestion (Barrett's esophagus)
    • GERD → intestinal metaplasia (Barrett's Esophagus) → low grade dysplasia → high grade dysplasia → adenocarcinoma
    • frequent consumption of very hot drinks
  • Presentation:
    • Esophageal cancer can develop over a long time without causing any signs or symptoms.
    • Trouble swallowing (Dysphagia)
      • starts with solid foods like meat, bread or raw vegetables
      • as the tumour grows, swallowing soft foods and liquids becomes more difficult
    • Fullness, pain, pressure, burning in the chest or throat
      • caused by food or fluids making their way down the esophagus
      • pain may be dull or sharp and feel like indigestion or heartburn
      • may feel like food is stuck behind the breastbone
      • may come and go
    • Vomiting or choking on food
    • Weight loss (anorexia, cachexia)
      • discomfort and pain may make it difficult to eat
      • can lead to anemia and dehydration
    • Coughing and hoarseness
      • if the tumour affects the laryngeal nerves that lead to the vocal cords, or if the vocal cords or laryngeal nerve become paralyzed
    • Coughing or vomiting blood
    • Aspiration pneumonia
      • if the tumour becomes very large it can cause food, liquids and saliva to spill over into the lungs
    • Severe pain
      • between the lungs, breastbone and spine
      • toward the back
  • Examination:
  • Investigations:
    • Imaging studies (raise suspicion)
    • X-rays (mediastinal masses)
    • US
    • CT scans (nodes; tumour)
    • MRI
    • bone scans (for mets)
    • barium swallow (for obstructions)
    • Biopsy
      • Endoscopic punch biopsy of Barrett's or esophageal mass (risk of perforating esophagus; bleeding)
      • Follow low-grade dysplasia every 1 to 2 years to prevent progression to high-grade dysplasia
  • Complications:
  • Treatment & Prognosis:
    • Surgery
      • Esophagectomy with gastric pull-up
      • Nissen Fundoplication (prevent GERD); laparoscopic
    • Radiation therapy
    • Chemotherapy
      • Anti-Cancer Drugs, Palliative, adjuvant following Esophagectomy
      • PPI (prevent GERD)
    • Supportive care
  • Prognosis:
    • 5-year survival
    • ~75% superficial lesions (non-invasive)
    • ~10-25% advanced (invasive) w/ curative resection


Pancreas

  • Pathogenesis:
    • Major types
      1. Adenocarcinoma (85-90%)
      2. Islet cell tumours
      3. Other
  • Epidemiology & Risk Factors:
    • Forth leading cause of cancer death in Canadian men and women
    • 5% of cancer deaths
    • Advanced age is a predisposing factor
    • Smoking
    • High fat diet
    • Having had a distal gastrectomy
  • Presentation:
    • Suspect pancreatic cancer in any elderly patient presenting with onset of painless jaundice
    • Can also present with pain
    • Islet cell tumours can present as metabolic disorders if they secrete insulin, glucagons, etc.
  • Examination:
  • Investigations:
  • Complications:
  • Treatment & Prognosis:
    • Treatment is resection if possible. Only 10-20% of tumours can be resected.
  • Prognosis:
    • With tumour resection there is a 3.5% five year survival rate
    • Unresectable tumours have a mean survival time of 3 months

Stomach

Gastric Adenocarcinoma

  • Pathogenesis:
  • Epidemiology & Risk Factors:
    • men over 50
    • smokers
    • poor diet (high in preserved food, low in fruits and vegetables)
    • H. pylori
  • Presentation:
    • progressive epigastric pain
    • general vague GI symptoms (heart burn, nausea, etc.)
    • weight loss
    • obstruction
    • distant metastases
    • most present late with 50% having distant metastases
  • Examination:
  • Investigations:
  • Complications:
  • Treatment & Prognosis:
    • surgery
    • chemotherapy as palliative treatment
    • 10 to 15% five year survival for advanced cancers
    • 90 to 95% five year survival for early cancers
  • Screening:

role and utility

    • no screening program in place
    • can use endoscopy to screen for lesions
    • risks
      • side effects associated with endoscopy, which may include perforation, cardiopulmonary events, aspiration pneumonia, and bleeding requiring hospitalization.
      • these side effects are rare
    • benefits
      • there would be no reduction in mortality from stomach cancer if screening program were implemented


  • Pathogenesis:
  • Epidemiology & Risk Factors:
  • Presentation:
  • Examination:
  • Investigations:
  • Complications:
  • Treatment & Prognosis: