Colorectal Cancer Diagnosis and Treatment

• The text covers esophageal, colon, rectal, anal, pancreatic, gastric, and liver cancers

ESOPHAGEAL CANCER

Epidemiology

• Esophageal cancer is rare, accounting for 1% of all cancers
• In the Western world, adenocarcinoma (AC) is more common
• Squamous cell carcinoma (SCC)is more prevalent worldwide
• Males are more likely to develop it
• For SCC, African Americans are typically 45+
• For AC, African Americans are generally aged 70 or older

Distinguishing Subtypes

Squamous Cell Carcinoma

• Risk factors include alcohol and smoking (most common), low socioeconomic status, poor diet, hot beverages, nitrosamines, irradiation, HPV, achalasia, Plummer-Vinson syndrome, and chemical injury
• Usually located in the middle third of the esophagus

Adenocarcinoma

• Risk factors include Barrett's esophagus (from GERD), obesity, tobacco, and radiation
• Protective factors include a healthy diet and H. pylori
• Usually located in the distal third of the esophagus

Presentation

• Dysphagia (difficulty swallowing)
• Odynophagia (painful swallowing)
• Weight loss, a loss of >10% indicates poor prognosis
• Vomiting
• Cough
• Hoarseness, indicating recurrent laryngeal n. paralysis
• Dyspnea (shortness of breath)

Diagnosis

• Often diagnosed at an advanced stage
• Gastroscopy with biopsy
• Endoscopic ultrasound (EUS)
• CT scan
• Liver parameters assessment

Treatment

• Surgery is usually the best option, potentially with pre-operative radiation therapy and/or chemotherapy, as well as post-operative immunotherapy (Paclitaxel, carboplatin)
• Inoperable cases require radical chemoradiotherapy
• Intracavital brachytherapy may be used
• Metastatic cases require symptomatic treatment, chemotherapy, plus immunotherapy (Nivolumab)
• Peri-operative chemotherapy may be used for cancer in the lower esophagus or gastric cancer

Progression and Prognosis

• Poor prognostic factors: tumor size greater than 5cm, weight loss >10%, esophageal obstruction, and high-grade tumor
• Can metastasize via lymphatic spread to the lungs, liver, or adrenal glands
• Generally has a poor prognosis

COLON CANCER

• Colon cancer mostly develops from polyps, so removing polyps or adenomas endoscopically decreases the risk

Epidemiology

• Is the 3rd most common cancer
• Accounts for 10% of cancer deaths
• Peak incidence occurs at 60-70 years old
• Incidence is equal in males and females

Risk Factors and Etiology

• Genetic factors: 5% of cases i.e FAP, Lynch syndrome, juvenile polyposis, or Peutz-Jeghers
• Inflammatory Bowel Disease (IBD): Ulcerative Colitis more so than Crohn's
• Poor diet: refined carbs, rich in fat, and low fiber
• Blood type O is linked
• Alcohol, smoking, obesity, and processed meat

Subtypes

• Adenocarcinomas without inherited genetic mutations: develop from adenomas- higher risk if the adenomas are large, dysplastic/metaplastic, sessile or flat, have villous architecture, or multiple polyps
• FAP (familial adenomatous polyposis - AD; APC mutation): extreme polyp formation in adolescence- which means there is nearly a 100% risk of colon cancer at 55 years of age- colon must be surgically removed i.e increased risk of other cancers is very high i.e. gastric, thyroid, and hepatoblastoma
• HNPCC/Lynch syndrome (AD, MSI): increased risk of other malignancies- endometrial, gastric, ovarian, renal, and intestinal cancer; Right-sided colon cancer

Presentation

• Iron deficiency anemia and blood in the stool- tumor bleed
• Altered bowel habits- diarrhea, constipation
• Hematochezia
• Abdominal pain
• Ileus- risk of obstruction

Right vs Left Sided

• Anemia indicates right-sided cancer
• Obstruction and pencil-shaped stool indicates left-sided cancer

Diagnosis

• Colonoscopy with biopsy
• After the biopsy, a CT scan of the abdomen and chest is needed- to search for metastasis
• Molecular testing is vital: KRAS, NRAS, BRAF, MSI, HER2, and FAP- if positive for Lynch or FAP- check up on family members
• Staging: DUKES, ASTLER-COLLER or AJCC/TNM

Treatment

• Surgery +/- other options (remove lymph nodes)
• Stage I + II: resection is the best option
• Stage III: surgery +/- post-op chemotherapy
• Stage IV: chemo + surgery- removing tumor + mets
• Chemotherapy (FOLFOX) + Panitumumab if positive for KRAS/BRAF mutation-note severe skin toxicity. VEGF(R)

Progression and Prognosis

• 20-25% of patients are diagnosed at metastatic stage- Liver is the most common site
• Prognostic factors: cancerous grade + lymphatic invasion + >4 lymph nodes involved + presurgical CEA >5
• 50% of the patients will relapse after relapse- 80% of relapses will be within 3 years

Other Info

• Screening: annual DRE from 40, fecal occult blood test from 50- colonoscopy; colonoscopy every 10 years from 50
• CEA: good for determining further treatment
• Location of cancer: left colon and sigmoid (36%) > right colon and cecum (27%) > rectum > transverse colon > anus > other

About Chemotherapy

• Not required in some instances
• Can be 1-2 drugs (Capecitabine and/or 5-FU)
• FOLFOX-5-Fu or CAPOX - capecitabine and oxiplatin
• Immunotherapy can also be used
• KRAS can predict resistance of anti-EGFR rec

RECTAL CANCER

Epidemiology

• Less prevalent than colon cancer
• Constitutes 16% of colorectal cancers

Risk Factors and Etiology

• Primarily the same as colon cancer

Subtypes

• Adenocarcinoma: vast majority
• SCC
• Neuroendocrine tumors

Presentation

• Bleeding from the anus: more typical for rectal cancer than colon cancer
• Constipation and/or diarrhea
• Abdominal pain: often crampy

Diagnosis

• Colonoscopy with biopsy
• CT/MRI to assess for metastasis

Treatment

• Stage I + II → surgery: TME (total mesorectal excision) Stage III → pre-op RT + surgery +/- post-op chemo
• Stage IV → surgery + chemo/RT

Progression and Prognosis

• 5-year survival (5YS) based on Dukes stage:
  • A: 80-90%
  • B: 70-80%
  • C: 30-50%

ANAL CANCER

Epidemiology

• More frequent in females
• Peak incidence is in the 50s

Risk Factors and Etiology

• HPV (16, 18): genital warts increase risk by 30x
• Immunodeficiency: HIV, immunosuppression
• Anal intercourse increases risk by 33x
• Smoking increases risk by 8x

Subtypes

• Depends on the level: overall, SCC is the most common
  • Proximal: adenocarcinoma
  • Distal + above dentate line: non-keratinizing SCC
  • Distal + below dentate line: keratinizing SCC
  • Anal margin: skin cancer

Presentation

• Bleeding is most common symptom
• Pain
• Mass-like Sensation
• Pruritus
• Asymptomatic

Treatment

• Conservative treatment: preserve anal sphincter: chemo + RT = curable in 80-90%
• If <2cm -> RT alone is less common
  • Surgery: only if conservative treatment fails

Progression and Prognosis

• 5-year survival (5YS) is generally 70-90%

PANCREATIC CANCER

Epidemiology

• Rare
• Contributes to 5% of cancer deaths
• Average age of diagnosis is 60-80 years old

Risk Factors and Etiology

• Smoking (primary factor) and alcohol
• Meaty and fatty diet
• Chronic pancreatitis, diabetes
• Genetic: Peutz-Jeghers, Dysplastic nevus syndrome, hereditary pancreatitis
• Partial gastrectomy

Subtypes

• 90% are ductal adenocarcinomas- these are typically located in the head of the pancreas

Presentation

• Fever and weight loss
• Back pain
• Impaired digestion due to enzymatic disturbances
• Impaired glycemic control due to beta cell destruction
• Jaundice: blockage of pancreatic ducts
• Painless gallbladder dilation + obstructive jaundice: Courvoisier sign, only evident if tumor is in head of pancreas
• Migratory thrombophlebitis: Trousseau sign
• Epigastric mass (late sign)

Pre-Malignant Lesions

• Pancreatic intraepithelial neoplasia (PanIN)
• Mucinous cysts
• Non-mucinous cysts

Diagnosis

Marker: CA 19.9 + lipase/amylase

• Diagnosis based on CT + biopsy/ Genetic testing: BRCA2, KRAS, TP53, CDK2NA, SMAD4 and USG, MRI, ERCP

Treatment

• Chemotherapy - FOLFIRINOX if healthy; milder regimen e.g., Gemcitabine
• Given high risk of Thrombosis the patient will need Apixaban
• Surgery - Done in around 20% of cases with a whipple procedure or pancreatectomy with chemo

###Progression and Prognosis

• Insidious growth over many years
• Very poor prognosis- often comes with early metastasis; to regional nodes, liver, lungs
• Perineural invasion may occur
• Tumor in head has slightly better prognosis- earlier symptoms

Other Info

Virchow's node is linked to left supraclavicular node enlargement.

GASTRIC CANCER

Epidemiology

• Most commonly adenocarcinoma
• Common in Japan & China, but decreasing in incidence
• Relatively common cause of cancer deaths
• More common in males, typically around 60 years old

Risk Factors and Etiology

• Risk factors depend on subtype, but can include adenomatous gastric polyps, partial gastrectomy, or family history
• Blood Type A also linked

Subtypes

• 95% are adenocarcinomas, including intestinal and diffuse
  • Intestinal AC occurs more frequently in males typically around 55 years old. Decreasing occurrence from chronic gastritis (H Pylori), nitrosamines, FAP and HNPCC
• Diffuse - Stable-uniform across contries
• May be related to EBV
• Better prognosis
• CDH1 Mutation: better prognosis

Presentation

• Epigastric pain: at times also in back when in advanced stage
• Vomiting at times with blood
• Anorexia and weight loss
• Dysphagia
• Iron-deficiency anemia
• Hepatomegaly
• Lymphadenopathy
• Epigastric mass
• Paraneoplastic syndromes: Acanthosis nigricans, Leser-Trelat syndrome

Diagnosis

• Gastroscopy with biopsy
• CT to assess for metastasis

Treatment

• Surgery is the only radical treatment, either total or partial gastrectomy
• Radical resection of stage 1B or higher combined with chemo
• Combine herceptin with treatment

Progression and Prognosis

Very poor prognosis

• T1: 50% 5-year survival
• Metastatic: Stage IV 3% survival
• Spread directly to GIT or hematogenously to liver or ovaries
• Bilateral-mucinous - Kulkenburg Tumor

Other Info

Specific lymph nodes associated

• Virchow's node (metastasis to left supraclavicular from abdominal cancer)
• Left axillary nodes
• Sister Mary Joseph's node
• Periumbilical

LIVER CANCER

Epidemiology

• 5th most common around the globe
• Asia and Africa have a higher prevalence of viral hepatitis

Risk Factors and Etiology

• Chronic hepatitis: HCV >> HBV
• Liver cirrhosis is related to alcoholism
• Aflatoxins
• Primary biliary cholangitis
• Genetic beta-catenin, TP53, and TERT
• Alphal-antitrypsin deficiency
• Obesity
• Wilson's disease
• Hemochromatosis

Subtypes

• Hepatocellular carcinoma: is the MC primary subtype liver cancer
• Fibrolamellar carcinoma: is MC in those under 35 years old
• Metastatic liver cancer: is the most common, primarily found in the lungs, colon, breast and pancreas

Presentation

• Non-specific symptoms early on
• Weight loss
• Painful mass on abdomen
• Symptoms of liver failure includes liver failure, spider angiomas, palmer erythema, and coagulation disturbances
• Paraneoplastic polycythemia

Diagnosis

• USG, CT, MRI
• High levels of AFP- is not diagnostic and therefore not used for screening

Treatment

• Local ablation radiofrequency
• Immunotherapy
• Surgical is cure
• Inoperable cases with Sorafenib

Progression and Prognosis

• Generally poor prognosis due to complications
• Tendency to invade portal vein
• Intrahepatic metastasis is MC

Questions cover the diagnosis, treatment and management of colorectal cancer. Topics include post-colonoscopy steps, genetic testing, surgical resection, the impact of KRAS mutations, MSI-H and diagnostic procedures for cancer.