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Gastrointestinal cancers (Colorectal cancer (staging (Local Treatment…
Gastrointestinal cancers
Colorectal cancer
- Third leading cause of death from cancer in both males and females
- 2nd most frequent cancer in developed countries
- Median age of diagnosis 60 years, begins increase at age 40, and rises with age
- identical in men and women
Etiology
- Genetic factors (only 5% of cases):
HNPCC (mut.MLH1,MSH2,6) -Lynch Syndrome
FAP (Familial Adenomatous Polyposis), (mut APC)
Adenomatous polyps
- Inflammatory bowel disease,
- Environmental factors,
- Diet (rich in fat and chol.),
- Cancer history
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Screening
- Annual Digital Rectal Examination starting at 40 years of age
- FOBT (fecal occult blood test) starting at 50 (sensitivity!) – if (+) - endoscopy
- Both combined reduce the risk of death by 30%
- Endoscopy q10years (begining at age 50) if average risk
common sites
- Large intestine:
36% in left colon (descending colon) & sigmoid colon
27% in right colon ascending colon) & cecum
16% in rectum
8% other
3% anus
Symptoms
- Right semicolon cancer:
abdominal pain, fatigue, anaemia, abdominal cavity tumor, diarrhea/constipation, obstructive symptoms
- Left semicolon cancer:
abdominal pain, bleeding, constipation alterneiting with diarrhea, obstructive symptoms
- Rectal cancer:
bleeding, constipation, abdominal pain, painful cramps, diarrhea
- guidlines for urgent referral of pats with suspected colorectal cancer based on symptoms presented (pat needs to have all of them):
-all ages:
definitie palpable right sided abdominal mass
definitie palpable rectal (not pelvic) mass
rectal bleeding with frequent defecation or looser stools ( or both) persistent over six weeks
iron deficiency anaemia without obvious cause
-age over 60:
rectal bleeding without anal symptoms.
frequent defecation or looser stools ( or both) persistent over six weeks without rectal bleeding
Histology
- Adenocarcinomas (90-95%)
- Mucinous adenocarcinoma
- Adenosquamous carcinoma
- Squamous cell carcinoma
- Small cell carcinoma
- Chorioncarcinoma
- Medullary cancer
- Carcinoid, Sarcoma
staging
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- 5-year survival:
Dukes A – 80-90%
Dukes B – 70-80%
Dukes C – 30 – 50%
- Local recurrences after surgery:
Dukes B – 15 - 30%
Dukes C – 20 - 50%
Prognostic factors
Grade
Lymphatic vessels invasion
(>4 lymph nodes involved
Pre-surgical CEA (serum tumor marker that is useful for assessing treatment response and detecting recurrence; not useful for screening) > 5
Local Treatment
- Early stage (colon, rectum)- A, B1, B2 – surgery
- B2(?), C rectal cancer – surgery + pre or postoperative RT +- CHT
- B2(?), C colon cancer - surgery +/- postoperative CHT
Total mesorectal excision (TME) – resulted in significant decrease of locoregional recurrence – from ~30% to 10%
Stage D
- Clinical presentation:
20% with advanced disease.
50% treated with curative surgery will develop advanced disease
80% of relapses will occur within tree years of primary surgery
50 % with advanced disease will present with liver metastases
20% with advanced disease have liver disease
treatment
- Intravenous CHT with 5-FU, antimetabolite, inhibiting DNA and RNA synthesis
- Topoisomease I inhibitors– irinotecan
- Capecitabine(Xeloda)
- Oxaliplatin
- Metastasectomy–upto2-3livermetsresection may prolong 5y survival up to 50% (lung mets – 25%)
- Bevcizumab–VEGFR monoclonal antibody
- Cetuximab, Panitumumab - EGFR monoclonal antibody
Anal canal cancer
- 1 –2% colorectal cancer
- Peak incidence in the 6th decade of life
- 4x more common in M than in F
Risk factors
HPV infection (esp.16, 18),
genital warts 30x,
immunodeficiency state [HIV 38x(hetero); 84x (homo), immunosupression 100x],
receptive anal sex in M 33x, cigarette smoking 8x
symptoms
bleeding 50%, pain 40%, mass-like sensation 25%, pruritus 15%, Asymptomatic 25%
Treatment
- Conservative
- CHT + RT 80 – 90% CR, 5-y survival 70 – 90%
- RT alone – if lesion < 2 cm ( EBRT+BT); but CHT+RT more common
- Surgery – in case of conservative tx failure
Esophageal cancer
- 1% of all cancers
- M > F, median age 60-65 years
- upper(20-33%), middle(33%), lower(33-50%)
- main types:
most common worldwide: SCC in upper 2/3 of esophagus
most common in Western countries: adenocarcinoma (due to Barrett esophagus) in distal 1/3 of esophagus
Risk factors
- tobacco and alcohol (most common causes)
- hot temp. of certain beverages and foods
- esophageal stricture
- low socioeconomic status
- diet, exposure to nitrosamines
- mediastinum radiotherapy
- Barret metaplasia (normal squamous epithelium -->glandular columnar epithelium)
symptoms
- Dysphagia, Odynophagia.
- Weight loss (>10% poor prognostic factor)
- Pain, Vomiting (hematemesis), Cough, Shortness of breath
- Hoarseness (involvement of recurrent laryngeal nerve) (commonly in SCC)
Diagnostic workup
- Upper GI endoscopy + biopsy
- EUS (endoscopic US)
- CT
- Liver tests
Prognostic factors
- Tumor > 5 cm
- Esophageal obstruction
- High grade
- Weight loss > 10%
Treatment
- If operable - surgery
- If medically inoperable – radical RT or RT+ CHT
- If local treatment not possible or metastatic disease – symptomatic treatment
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lymph node involvement
- Upper 1/3-cervical nodes
- Middle 1/3-mediastinal or tracheobronchial nodes
- Lower 1/3-celiac and gastric nodes
Gastric cancer
- Second largest cause of cancer related death worldwide.
- Most common in Japan and China
- During past 50 years, incidence and mortality from gastric cancer decreased worldwide, esp. in developed countries
- M > F, median age 60 years
Risk Factors
- H. Pylori infection and atrophic gastritis.
- Pernicious anaemia.
- Adenomatous gastric polyps.
- partial gastrectomy.
- abnormalities in E-cadherin gene.
- Family history, Diet
Sings & Symptoms
- symptoms:
Pain (epigastric, back[advanced]), anorexia, vomiting, dysphagia, iron deficiency anaemia, Weight loss, hematemesis or melaena
- Sings:
cachexia, weight loss, anaemia, epigastric pain, hepatomegaly, palpable left supraclavicaualr node (Troisier's sign)
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Treatment
- Surgery is the mainstay of treatment
(total or partial gastrectomy with lymphadenectomy)
- Radically resected stage IB or higher - chemoradiation
(5 cycles 5FU/LV, 2nd & 3rd with RT)
- Recently neoadjuvant ECFx3 – surgery – adjuvant ECFx3
(as per MAGIC trial)
Prognosis
- 5-y survival for T1 –2 N0 and T1N1 – ~50%
- StageII–~30%
- Stage III – ~ 13%
- Stage IV– ~ 3%
Pancreatic cancer
- 10th most common malignancy, 4th most common cancer death cause
- Peak incidence 7th or 8th decade
- 95% adenocarcinoma
Risk Factors
- Family history, Diet
- partial gastrectomy.
- smoking
Sings & Symptoms
- Sings:
cachexia, anaemia, epigastric mass (late), palpable gall bladder (Courvoisier's sign)
- symptoms:
obstructive jaundice - dark urine, pale stools, pruritus, Pain (epigastric, back[common]), anorexia, vomiting, Weight loss, hematemesis or melaena (late)
Diagnostic workup
- Biopsy – necessary, but may be abandoned if surgical removal planned
- US, TK, MRI, ERCP
Treatment
- If operable – radical surgery– eg. Whipple procedure or pancreatectomy in pancreatic tail tumors (20% pts eligible) +/- CHT
- In locally advanced disease–CHT(gemcytabine), CHT/RT
- Metastatic disease– chemotherapy (GEM, 5FU, POLFIRINOX, nab-paclitaxel)
5 year survival rates
- overall survival < 5%
- with resection 18-24%
- without resection < 1%
Liver cancer
- HCC – hepatocellular ca – most common primary liver tumor
- 5th most common cancer worldwide
- Leading cause of cancer mortality
- Highest incidence in Orient and Africa – HBV infection
- In curative resections, recurrence rate 50-70%
Risk factors
- Cirrhosis (80% patients)
- If HBV infection often without cirrhosis
- Hemochromatosis
- Alcohol consumption
- Alfa1 – antitrypsin deficiency
- Food contamination with aflatoxin B1 (Aspergillus flavus)
Symptoms
- abdominal pain, weight loss, decompensation of liver function
- Diagnosis: imaging, AFP level
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- Prognosis: related to the success of surgery 5-y OS 20-40%