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Digestive system neoplasms (COLORECTAL CANCER (RISK FACTORS (GENETIC…
Digestive system neoplasms
COLORECTAL CANCER
2nd most commonly cancer in women and 3rd most common in men
RISK FACTORS
AGE:
90% of cases occur after the age of 50
Gender:
CRC & Adenomas are higher in men than in women
Family history of sporadic colorectal cancer or adenomatous polyps
Adenomatous polyps
especially villous and tubulovillous histology
history of sporadic colorectal cancer
GENETIC
Lynch syndrome (hereditary nonpolyposis colorectal cancer) (HNPCC)
autosomal dominant
mutations in DNA mismatch repair genes
increased risk of other cancers (endometrial, stomach, ovarian, pancreas, urinary tract, biliary tract, brain)
cancer at an early age (before 50)
involvement of the right colon (about 70% of lesions located proximally to the splenic flexure)
Lack of sensitivity on 5 FU
Familial adenomatous polyposis (FAP)
autosomal dominant
multiple colorectal adenomatous polyps
less than 1% of colorectal cancers, Usually distal, L sided location
mutations in the APC gene (chromosome 5)
Polyps develop <25 years of age
colonic cancer occurs in nearly 100% of untreated individuals by the age of 50
Inflammatory bowel disease
Cancers develop in areas of dysplasia rather than from polyps
Greatest risk with pancolitis and long-standing disease
PSC increases risk
Risk smaller in left-sided disease.
Isolated proctitis: no increase in risk
The increase in risk of colon cancer begins about 10 years after the initial diagnosis of pancolitis, and at 15 to 20 years for colitis limited to the left colon.
Cigarette smoking
Ureterocolic anastomoses
Prior pelvic irradiation
Diet – red and processed meat
Alcohol consumption
PROTECTIVE FACTORS
regular physical activity
diet high in fruits and vegetables
folic acid from food
dietary fiber
calcium supplementation
regular use of aspirin or NSAIDs
HRT in postmenopausal women
Pathogenesis
Most CRCs arise from adenomas (90%)
Progression from adenoma to carcinoma - 10 years
Factors determining risk of malignant transformation with colic adenomatous polyps
High risk:
large size (>1.5 cm), flat or sessile, sever dysplasia, presence of squamous metaplasia, villous architecture, polyposis syndrome (multiple polyps)
low risk:
small size (<1 cm), pedunculated, mild dysplasia, no metaplastic area, tubular architecture, single polyp
PATHOLOGY
most commonly adenocarcinoma
Synchronous tumors
two or more distinct primary tumors diagnosed within 6 months of an initial CRC, separated by normal bowel, and not due to direct extension or metastasis
in up to 5% of patients
presence of synchronous cancers should raise the clinical suspicion for Lynch Syndrome
CLINICAL PRESENTATION
majority of patients with early stage colon cancer do not have symptoms
Right semicolon cancer:
abdominal pain, fatigue, iron deficiency 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, Tenesmus
DIAGNOSIS
colonoscopy with biopsy
rectal digital examination
double contrast barium enema
virtual colonoscopy (CT)
endosonography
metastases: abdominal CT and ultrasonography, chest X-ray
DISTANT METASTASES
Direct extension, Hematogenous (liver [most common], lungs), lymph nodes.
25% of patients have metastases at the time of diagnosis
TREATMENT
STAGE I: SURGICAL RESECTION (> 90% 5 YEAR SURVIVAL)
STAGE II: RESECTION +/- ADJUVANT THERAPY (70-85%)
STAGE III: RESECTION + ADJUVANT CHEMOTHERAPY (30-60%)
STAGE IV: CHEMOTHERAPY ( ≈ 5%)
CEA
a serum level of carcinoembryonic antigen (CEA) is usually obtained preoperatively
not helpful diagnostically – sensitivity 46 %
elevated CEA levels should normalize following curative resection; if they do not, residual disease should be suspected.
PALLIATIVE THERAPY
COLON CANCER – palliative operation (for mechanical obstruction)
RECTALCANCER – laser therapy
MULTIPLE LIVER METASTASES
– chemotherapy with 5 FU * leucovorin + oxaliplatin or irinotecan
– radiofrequency ablation
SCREENING TESTS
for asymptomatic adults aged 50 years or older:
Colonoscopy every 10 years
Sigmoidoscopy every 5 years
Fecal occult blood testing (FOBT) or fecal immunochemical test (FIT) every 1-2 years
A NEGATIVE FOBT DOES NOT RULE OUT CANCER!
FAMILY HISTORY OF SPORADIC CRC OR ADENOMATOUS COLONIC POLYPS
AT AGE 40 OR 10 YEARS EARLIER THAN THE ONSET OF CRC IN THE FAMILY MEMBER
FAMILIAL ADENOMATOUS POLYPOSIS (FAP)
AT AGE 10
LYNCH SYNDROME (HNPCC) AT AGE 25
Anal canal cancer
4x more common in M than in F
1 –2% colorectal cancer
Risk factors
HPV infection (esp.16, 18)
genital warts 30x
immunodeficiency state,
receptive anal sex in M 33x, cigarette smoking 8x
symptoms
bleeding 50%, pain 40%, mass-like sensation 25%, pruritus 15%, Asymptomatic 25%
Treatment
CHT + RT 80 – 90% CR, 5-y survival 70 – 90%
Surgery – in case of conservative tx failure
TRANSANAL EXCISION – small tumors without lymph node involvement
LOW ANTERIOR RESECTION – sufficient distance from anus – usually 5cm
ABDOMINOPERINEAL RESECTION– if too close to anus
PELVIC EXENTERATION – in case of invasion of pelvic organs
NEOADJUVANT THERAPY– pre-operative radiotherapy / chemotherapy in locally advanced rectal cancer
GASTRIC CANCER
5 most common malignancy in the world, after cancers of the lung, breast, colorectum and prostate
more cancers of the gastric cardia
M : F = 2: 1
3 leading cause of cancer death in both sexes
Most cases after the age of 50
95% are adenocarcinomas
small cell carcinomas and squamous cell carcinomas are rare
HISTOLOGY
Intestinal type
more common in males and older age groups
likely linked to environmental factors
multistep progression initiated by H. pylori infection
well-preserved intercellular adhesion molecules
Diffuse or infiltrative type
frequent in both sexes
common in younger age groups
has a worse prognosis than the intestinal type
defective cell adhesion
can be induced by H. pylori but development less clear
Highly metastatic, rapid progression
Linitis plastica – stomach wall infiltration (rigid thickened stomach wall)
RISK FACTORS
Helicobacter pylori infection
family history of gastric cancer
dietary factors
fried food, processed meat (mutagenic N-nitroso compounds), salt
diet low in fresh fruit and vegetables
smoking, gastric surgery
Pernicious anaemia, Adenomatous gastric polyps
Helicobacter pylori infection
Results in:
asymptomatic or Chronic antral gastritis,
Peptic ulcers (duodenal and gastric)
Gastric cancer.
SPREADING
lymph node metastases:
along the greater & lesser curvature, celiac trunk lymph nodes, mesenterial lymph nodes, paraaortal LN
haematogenous metastases:
liver, lung, bone, brain
organ involvement:
esophagus, duodenum, colon, pancreas
peritoneal involvement
ascites,Krukenberg's tumor (ovaries)
DIAGNOSIS
CLINICAL PRESENTATION
weight loss → cachexia
abdominal discomfort → pain
nausea and vomiting
acute bleeding with melaena or hematemesis
anorexia (loss of appetite), early satiety, aversion to meat
low fever, occult gastrointestinal bleeding with or without iron deficiency anemia
PHYSICAL EXAMINATION
palpable mass in the upper abdomen
hepatomegaly (due to metastases)
ascites
Virchow's node (left supraclavicular node)
periumbilical nodule (Sister Mary Joseph's node)
palpable left supraclavicaualr node (Troisier's sign)
upper endoscopy with multiple biopsies
endosonography (assessing tumor depth and lymph node involvement)
looking for metastases: abdomen sonography, abdominal CT, chest radiography
TREATMENT
SURGERY
subtotal / total gastrectomy plus lymph node dissection +/- splenectomy
lesions in the upper third of the stomach: total gastrectomy
for lesions in the lower two-thirds: subtotal gastrectomy
ENDOSCOPIC MUCOSAL RESECTION
in small early gastric cancer without lymph node involvement
endoscopic ultrasound to determine the depth of the lesion and lymph node status
intramucosal injection of saline to raise the lesion
resection with electrocautery
Palliative therapy
Approx. 50% of patients have advanced incurable disease at the time of initial presentation.
Even those who undergo potentially curative resection have high rates of distant and local recurrence.
systemic chemotherapy for patients with advanced gastric cancer
Local palliation:
gastric outlet obstruction caused by tumor: laser therapy, palliative gastrojejunostomy, stent
percutaneous jejunostomy (feeding tube).
HP-eradication therapy
GASTRIC LYMPHOMA
3% of gastric malignancies
usually B-cell origin (85%)
MALT-type marginal zone B-cell lymphoma
diffuse large B-cell lymphoma
90% of patients are infected with H.pylori
T-cell lymphomas are frequently associated with celiac sprue
abdominal pain and discomfort
fever and night sweats are uncommon
Endoscopy
A mass or polypoid lesion with or without ulceration
Benign-appearing gastric ulcer
Nodularity
Thickened, cerebroid gastric folds
Treatment
H.pylori eradication in MALT lymphoma
chemotherapy
usually no need for surgery
prognosis much better compared to gastric cancers
ESOPHAGEAL CANCER
8 most common cancer worldwide
6 most common cause of death
Male > female
Very poor survival
upper(20-33%), middle(33%), lower(33-50%)
pathology
Squamous cell carcinoma (SCC)
Usually the midportion of the esophagus. (upper 2/3)
SCC is more common than AC.
Adenocarcinoma (AC)
Usually the lower third of the esophagus.
Most cases arise from Barrett’s metaplasia.
50% of patients were previously asymptomatic
20% of patients had had long-standing and severe symptoms of GERD
Risk factors
SCC: smoking, alcohol, hot beverages, head or neck cancer, mediastinal irradiation, low socioeconomic status, achalasia, caustic injury, tylosis, Plummer-Vinson syndrome
AC: GERD, Barrett’s esophagus, smoking, obesity, mediastinal irradiation.
DIAGNOSIS
Presentation
AC and SCC have similar symptoms
usually occur in advanced disease
progressive solid food dysphagia, pain, weight loss, anorexia, regurgitation of saliva and food
tracheobronchial fistula, hoarseness (commonly in SCC), dyspnea, anaemia, aspiration pneumonia, hematemesis
ENDOSCOPY: biopsy – to confirm diagnosis
CHEST RADIOGRAPH: widening of the mediastinum or posterior tracheal indentation
BARIUM SWALLOW: invasion of nearby structures, presence of fistulae
CT: involvement of the mediastinal, perigastric, or celiac lymph nodes
EUS: involvement of the mediastinal, perigastric, or celiac lymph nodes
5 YEAR SURVIVAL
I: 50,3% / IIa: 22,5%, IIb: 22,5% / III:16,7% / IV: 0
TREATMENT
ESOPHAGECTOMY, BYPASS, ENDOTHORACIC ENDOESOPHAGEAL PULL-THROUGH
RADIOCHEMOTHERAPY, EXTERNAL BEAM RADIATION, INTRACAVITARY RADIATION
LASER THERAPY, PHOTODYNAMIC THERAPY, STENTS
Palliative
Surgical methods of palliation (eg, palliative esophagectomy and surgical bypass) provide limited benefit and are associated with substantial morbidity
preferred treatment for inoperable patients with local tumor invasion of the airway or aorta, or extraregional abdominal metastases, is endoscopic therapy, stent placement, RT, or concurrent chemoradiotherapy
lymph node involvement
Upper 1/3-cervical nodes
Middle 1/3-mediastinal or tracheobronchial nodes
Lower 1/3-celiac and gastric nodes