Colon Cancer

Colorectal adenocarcinoma — presenting with anemia, obstruction, or GI bleeding

Symptoms / Associated Sx

  • Change in bowel habits (caliber narrowing, alternating constipation/diarrhea)

  • Rectal bleeding, hematochezia, or occult blood in stool

  • Iron deficiency anemia (fatigue, pallor, dyspnea)

  • Abdominal pain, cramping (obstruction); palpable abdominal mass

  • Weight loss, anorexia, night sweats (advanced disease)

Denies

  • Normal colonoscopy within 5–10 years (reduces but does not eliminate risk — interval cancers occur)

  • Fever, diarrhea, sick contacts (rules out infectious colitis as primary if absent)

  • Young age without family history/IBD (reduces likelihood but does not eliminate)

Social History (SHx)

Age >45 (screening age), family history of CRC or polyps (FAP, HNPCC/Lynch syndrome), personal history of IBD, prior polyps, red meat/processed food diet, obesity, smoking, alcohol, low physical activity.

Main Etiology

  • Sporadic (75%): adenoma → carcinoma sequence over 10–15 years

  • Hereditary (25%): Lynch syndrome/HNPCC (~3%), FAP, MUTYH-associated polyposis

  • IBD-associated (Crohn's or UC — increased risk after 8–10 years of disease)

Most Common DDx

  • Diverticulitis (LLQ pain + fever + leukocytosis; CT shows pericolonic stranding without mass; colonoscopy 4–6 weeks later mandatory to exclude malignancy)

  • IBD (younger patient; chronic bloody diarrhea; fecal calprotectin elevated; colonoscopy shows inflammatory changes without mass; biopsy distinguishes)

  • Iron deficiency anemia from other causes (dietary, menstrual, celiac — colonoscopy and upper endoscopy needed to rule out GI source before attributing to non-GI cause in patients >45)

  • Hemorrhoids (painless bright red rectal bleeding; anoscopy confirms; does not cause anemia unless massive; colonoscopy still needed to rule out proximal cancer)

  • Ischemic colitis (elderly + vascular disease + bloody diarrhea; CT wall thickening; colonoscopy shows mucosal ischemia without mass)

  • Appendiceal cancer or cecal carcinoid (may mimic appendicitis; incidental finding at surgery; CT staging)

DATA

  • CBC (iron deficiency anemia — microcytic); CMP (LFTs — liver mets); CEA (baseline tumor marker — not diagnostic; used for monitoring)

  • Colonoscopy with biopsy (gold standard diagnosis)

  • CT chest/abdomen/pelvis with contrast (staging — liver mets, lymph nodes, peritoneal disease)

  • MRI pelvis (rectal cancer — local staging, sphincter involvement)

  • PET scan (recurrence or metastatic disease evaluation)

  • Microsatellite instability (MSI) / MMR testing on biopsy (guides immunotherapy eligibility)

Home Meds

  • NSAIDs/aspirin (note — aspirin has chemopreventive role; discuss continuation with oncology)

  • Anticoagulants (hold peri-procedurally); iron supplements (initiate if iron deficient)

Plan

  • Colonoscopy + biopsy for diagnosis; CT chest/abdomen/pelvis for staging

  • Multidisciplinary tumor board: surgery + oncology + gastroenterology + radiation oncology

  • Anemia management: IV iron (ferric carboxymaltose 500–1000 mg IV) if iron deficient; pRBCs if symptomatic or Hgb <7 (or <8 if cardiovascular disease)

  • Obstruction: SEMS (colon stent) as bridge to surgery or palliation; emergent surgery if complete obstruction + perforation

  • Bleeding: Colonoscopic hemostasis; IR embolization; surgery if uncontrolled

  • Surgical resection (curative intent, stage I–III): Laparoscopic or open colectomy; lymph node dissection; hepatic resection for isolated liver mets if resectable

  • Adjuvant chemotherapy (stage III and selected stage II high-risk): FOLFOX (oxaliplatin + leucovorin + 5-fluorouracil) × 6 months

  • Metastatic CRC (stage IV): FOLFOX or FOLFIRI ± bevacizumab or cetuximab (KRAS wild-type); MSI-H → pembrolizumab (first-line)

  • Genetic testing: MMR/MSI, KRAS, NRAS, BRAF, HER2 (guides targeted therapy)

  • Lynch syndrome testing if age <50, family history, or MSI-H — genetic counseling

  • CBC, CMP, CEA trending; nutritional support + dietitian; PT/OT; palliative care consult if metastatic

  • Discharge: Oncology follow-up within 1–2 weeks; CEA trending; colonoscopy 1 year post-resection; genetic counseling if indicated; family member screening recommendations

Red Flags

  • Complete bowel obstruction + perforation → emergent surgery

  • Massive GI bleeding from tumor → urgent colonoscopic or IR hemostasis; transfuse actively

  • Peritoneal carcinomatosis + massive ascites → malignant ascites; palliative paracentesis; tunneled catheter

  • MSI-H / Lynch syndrome → immunotherapy eligible; family screening mandatory

  • New liver lesions + CRC history → CT staging for metastasis; hepatic resection consult if isolated

Senior IM Resident Pearls

  • CEA is not a screening tool — used for post-treatment monitoring; elevated CEA at baseline predicts advanced stage; CEA rise post-resection suggests recurrence

  • MSI-H / dMMR CRC: Best predictor of response to pembrolizumab (PD-1 inhibitor); first-line immunotherapy for metastatic MSI-H CRC (KEYNOTE-177 trial)

  • KRAS/NRAS mutations (~50% of CRC) — predict resistance to anti-EGFR agents (cetuximab, panitumumab); always test before using these agents

  • Lynch syndrome (HNPCC): Autosomal dominant; MLH1/MSH2/MSH6/PMS2 mutations; lifetime CRC risk ~40–80%; also risk of endometrial, ovarian, urologic cancers — genetic counseling + family screening

  • Common mistake: Attributing rectal bleeding to hemorrhoids without colonoscopy in patients >45 — colorectal cancer must be excluded regardless of hemorrhoid presence

Esophageal Cancer

Squamous cell carcinoma (proximal/mid esophagus) or adenocarcinoma (distal, Barrett's-related) presenting with dysphagia and weight loss

Symptoms / Associated Sx

  • Progressive dysphagia — solids first, then liquids (classic malignant pattern)

  • Unintentional weight loss, anorexia, cachexia

  • Odynophagia, regurgitation, vomiting undigested food

  • Hoarseness (recurrent laryngeal nerve involvement), cough (tracheoesophageal fistula)

  • Chest or back pain (mediastinal invasion)

  • Iron deficiency anemia (chronic blood loss)

Denies

  • Intermittent dysphagia for solids only without progression (rules out malignancy; favors Schatzki ring or EoE)

  • Dysphagia to liquids from onset (rules out mechanical obstruction; favors achalasia or neuromuscular)

  • Recent GERD treatment without alarm features (reduces Barrett's-related adenocarcinoma likelihood if compliant)

Social History (SHx)

Tobacco + alcohol (SCC risk factors — synergistic); GERD/Barrett's esophagus (adenocarcinoma); obesity (adenocarcinoma risk); prior caustic injury; achalasia (SCC risk); head/neck radiation; Plummer-Vinson syndrome (iron deficiency + esophageal webs → SCC).

Main Etiology

  • SCC (proximal/mid-esophagus): tobacco, alcohol, achalasia, caustic injury, head/neck radiation

  • Adenocarcinoma (distal/GEJ): GERD → Barrett's esophagus → dysplasia → adenocarcinoma; obesity, male sex

Most Common DDx

  • GERD-related peptic stricture (chronic heartburn history; lower esophageal narrowing; no mass; biopsies benign; responds to dilation + PPI)

  • EoE (young male; atopy; recurrent food impaction; biopsy ≥15 eos/hpf; no mass; responds to topical steroids)

  • Achalasia (dysphagia to solids AND liquids; regurgitation of undigested food; barium "bird's beak"; manometry — aperistalsis + incomplete LES relaxation; no mass on EGD)

  • Mediastinal malignancy with extrinsic compression (lymphoma, lung cancer — CT shows mediastinal mass; esophagus compressed externally; EGD shows extrinsic compression not intrinsic mass)

  • Pharyngeal/laryngeal cancer (hoarseness + dysphagia; ENT evaluation + laryngoscopy; direct extension to esophagus)

  • Esophageal leiomyoma or GIST (benign intramural mass; smooth overlying mucosa; EUS distinguishes from malignancy)

DATA

  • CBC (anemia — iron deficiency); CMP (albumin — nutritional status)

  • EGD with biopsy (diagnosis); EUS (depth of invasion, lymph node involvement — most accurate for local staging)

  • CT chest/abdomen/pelvis (distant staging — liver mets, lung mets, celiac nodes)

  • PET scan (metastatic disease — upstages ~15–20% of patients thought to be resectable)

  • Bronchoscopy (if upper/mid SCC — tracheobronchial invasion assessment before resection)

Home Meds

  • PPIs (continue — reduce aspiration risk and mucosal injury); anticoagulants (hold peri-procedurally)

  • Pain medications (optimize — nutritional support and comfort focus)

Plan

  • EGD + biopsy → staging CT + EUS + PET → multidisciplinary tumor board

  • Localized disease (stage I–II), resectable:

    • Adenocarcinoma: neoadjuvant chemoradiotherapy (carboplatin + paclitaxel + RT — CROSS protocol) → esophagectomy

    • SCC: definitive chemoradiation (cisplatin + 5-FU + RT) — may be curative; or neoadjuvant CRT → surgery

  • Locally advanced (stage III) or borderline resectable: Neoadjuvant CRT → restaging → surgery if good response

  • Metastatic (stage IV):

    • Adenocarcinoma: FOLFOX or cisplatin + 5-FU ± trastuzumab (HER2+) or nivolumab (PD-L1 high)

    • SCC: cisplatin + 5-FU or carboplatin + paclitaxel; nivolumab if PD-L1 positive

  • Nutritional support: PEG tube or NJ tube if unable to maintain intake; dietitian referral

  • Esophageal dilation or palliative SEMS (stent) if severe dysphagia — immediate palliation while awaiting therapy

  • Pain management: opioids PRN; radiation for bone mets; palliative care consult early

  • Dysphagia grading; weight monitoring; albumin/prealbumin; CBC, CMP, CEA trending

  • PT/OT — deconditioning common; speech therapy for aspiration risk

  • Discharge: Oncology follow-up within 1 week; nutritional counseling; soft/liquid diet; PEG tube care if placed; palliative care if metastatic; advance directive discussion

Red Flags

  • Tracheobronchial fistula (cough with eating, aspiration) → NPO; stent placement; thoracic surgery + oncology

  • Massive GI bleeding from tumor → urgent endoscopic or IR hemostasis; transfuse

  • Severe dysphagia/odynophagia + weight loss >10% body weight → emergent nutritional support (PEG/NJ)

  • SVC syndrome (facial/arm swelling, venous engorgement) → mediastinal invasion → radiation + oncology

  • Cervical esophageal cancer with airway compromise → intubation consideration before stenting

Senior IM Resident Pearls

  • EUS is the most accurate tool for T-staging (depth of invasion) and N-staging (periesophageal nodes) — essential before surgical planning

  • PET upstages ~15–20% of patients thought to be resectable — always do PET before committing to surgery

  • CROSS protocol: Carboplatin + paclitaxel + concurrent RT × 5 weeks → surgery; improved R0 resection rates and OS for both SCC and adenocarcinoma

  • HER2 testing mandatory for metastatic adenocarcinoma — trastuzumab added to first-line chemo improves OS in HER2-positive disease (ToGA trial)

  • Common mistake: Stenting before definitive therapy planning — palliative SEMS should not preclude definitive CRT; discuss with oncology before placing stent if potentially resectable

  • Common mistake: Attributing progressive dysphagia to GERD in patients >50 without EGD — malignancy must be excluded urgently

Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) — often presents with painless obstructive jaundice, weight loss, and new-onset diabetes

Symptoms / Associated Sx

  • Painless progressive jaundice, dark urine, pale stools, pruritus (classic presentation — head of pancreas)

  • Unintentional weight loss, anorexia, cachexia

  • Epigastric or back pain (often dull, boring — body/tail involvement)

  • New-onset diabetes mellitus in patient >50 with weight loss (paraneoplastic)

  • Palpable gallbladder without tenderness (Courvoisier's sign)

  • Trousseau's syndrome (migratory superficial thrombophlebitis)

  • Steatorrhea, malabsorption (exocrine insufficiency)

Denies

  • Prior gallstones (reduces choledocholithiasis/cholangitis likelihood — though can coexist)

  • Fever (rules out acute cholangitis as primary if absent — though can complicate pancreatic cancer with biliary obstruction)

  • History of biliary instrumentation (rules out stent occlusion)

Social History (SHx)

Smoking (most modifiable risk factor), chronic pancreatitis, new-onset DM in elderly, family history of PDAC or BRCA1/2/PALB2 mutations, obesity, alcohol (chronic pancreatitis), hereditary pancreatitis.

Main Etiology

  • Sporadic PDAC (90%) — K-ras mutation in ~95%

  • Hereditary: BRCA1/2, PALB2, ATM, CDKN2A, Lynch syndrome

  • Chronic pancreatitis → increased risk; new-onset DM in elderly can be paraneoplastic

Most Common DDx

  • Choledocholithiasis (CBD stone causing obstructive jaundice; colicky pain; RUQ tenderness; MRCP shows stone; no mass; responds to ERCP)

  • Acute cholangitis (Charcot's triad; CBD dilation; fever; WBC elevated; stone or stent on imaging; no pancreatic mass)

  • Autoimmune pancreatitis (type 1 — IgG4-related; focal pancreatic mass mimicking PDAC; elevated serum IgG4; sausage-shaped pancreas; responds to steroids — biopsy and steroid trial before surgery)

  • Cholangiocarcinoma (bile duct cancer — biliary stricture without pancreatic mass; CA 19-9 and CEA elevated; MRCP shows bile duct narrowing; brushings/biopsy)

  • Ampullary cancer (periampullary carcinoma — fluctuating jaundice; biliary bleeding; EGD shows mass at papilla; better prognosis than PDAC)

  • Chronic pancreatitis with inflammatory mass (prior pancreatitis episodes; calcifications on CT; mass may simulate PDAC; EUS-guided biopsy distinguishes)

DATA

  • LFTs (obstructive pattern — ALP/GGT/bilirubin elevated; direct hyperbilirubinemia)

  • CBC, CMP, PT/INR (coagulopathy from vitamin K malabsorption)

  • CA 19-9 (tumor marker — not diagnostic alone; elevated in ~80%; used for monitoring and prognosis)

  • CEA; IgG4 (if autoimmune pancreatitis suspected)

  • CT abdomen/pelvis with pancreatic protocol (3-phase — best for mass characterization + vascular involvement)

  • MRCP (biliary and pancreatic ductal anatomy; "double duct sign" = PDAC until proven otherwise)

  • EUS + fine-needle aspiration (EUS-FNA) — most accurate for tissue diagnosis and local staging

  • ERCP (biliary drainage via stent if obstructive jaundice; brushings for cytology)

  • PET scan (metastatic staging)

  • Genetic testing (germline BRCA1/2, PALB2, ATM if resectable — guides adjuvant therapy)

Home Meds

  • Anticoagulants (hold peri-procedurally); diabetes medications (adjust if new/worsening DM)

  • Proton pump inhibitors (continue); pancreatic enzyme replacement therapy (PERT) if steatorrhea

Plan

  • CT pancreatic protocol + EUS-FNA for tissue diagnosis + staging → multidisciplinary tumor board

  • Resectability criteria (Borderline Resectable Pancreatic Cancer — BRPC criteria):

    • Resectable: no vascular involvement (SMA, celiac, portal/SMV)

    • Borderline resectable: contact ≤180° of SMA, or short segment portal/SMV involvement

    • Locally advanced/unresectable: encasement >180° of SMA or celiac axis; unreconstructable portal/SMV

  • Resectable PDAC:

    • Pancreaticoduodenectomy (Whipple) for head/uncinate; distal pancreatectomy for body/tail

    • Adjuvant chemotherapy: mFOLFIRINOX × 6 months (if good PS) or gemcitabine + capecitabine × 6 months

  • Borderline resectable: Neoadjuvant chemotherapy (FOLFIRINOX or gemcitabine + nab-paclitaxel) → restaging → surgery if downsized

  • Locally advanced/metastatic:

    • FOLFIRINOX (oxaliplatin + irinotecan + leucovorin + 5-FU) if good PS (ECOG 0–1)

    • Gemcitabine + nab-paclitaxel (second option or PS 2)

    • BRCA1/2 or PALB2 mutations + platinum-responsive → olaparib maintenance (POLO trial)

  • Biliary obstruction management:

    • ERCP with biliary stent (SEMS for unresectable; plastic stent if surgery planned — less interference)

    • PTBD if ERCP fails

  • Pancreatic enzyme replacement (PERT): pancrelipase (Creon) 40,000–72,000 units with main meals; 24,000 units with snacks — for exocrine insufficiency and steatorrhea

  • Diabetes management: insulin if poorly controlled; oral agents often insufficient in PDAC

  • Nutritional support: dietitian; high-calorie/protein supplements; NJ/PEG if unable to maintain PO

  • Pain management: celiac plexus block (EUS-guided or CT-guided) for refractory pancreatic pain; opioids; gabapentin adjunct

  • VTE prophylaxis: PDAC has very high VTE risk — LMWH (enoxaparin) recommended; Trousseau's warrants anticoagulation

  • Early palliative care consult (regardless of stage)

  • Trend CA 19-9, CBC, CMP, albumin; PT/OT; advance directive discussion

  • Discharge: Oncology + surgery follow-up within 1 week; PERT dosing education; diabetes management plan; pain regimen; palliative care follow-up; advance directive; genetic counseling if BRCA/PALB2

Red Flags

  • Obstructive jaundice + cholangitis → urgent ERCP with biliary stent (biliary decompression before surgery or chemo)

  • Gastric outlet obstruction (duodenal compression) → duodenal stent or surgical bypass (gastrojejunostomy)

  • Massive VTE (Trousseau's) → anticoagulate; LMWH preferred over warfarin in cancer-associated VTE

  • Autoimmune pancreatitis mistaken for PDAC → do not resect without adequate workup; IgG4 elevation + steroid trial response can avoid unnecessary Whipple

  • New-onset DM + weight loss + age >50 + elevated CA 19-9 → CT pancreatic protocol urgently

Senior IM Resident Pearls

  • "Double duct sign" (concurrent dilation of CBD and main pancreatic duct) on MRCP/ERCP = periampullary malignancy until proven otherwise; CT + EUS-FNA required

  • Courvoisier's sign (palpable non-tender gallbladder + jaundice) suggests malignant biliary obstruction (not stones — stones cause fibrotic, non-distensible GB)

  • Autoimmune pancreatitis (AIP type 1): IgG4-related; "sausage pancreas" on CT; responds dramatically to prednisone 40 mg daily — steroid trial before Whipple if diagnosis uncertain

  • CA 19-9 has limited sensitivity (~80%) and specificity — cannot diagnose or exclude PDAC alone; elevated in cholangitis, cirrhosis, and other GI malignancies; Lewis antigen-negative patients (~10%) do not produce CA 19-9

  • Common mistake: Not testing for BRCA/PALB2 in resectable PDAC — germline mutations guide adjuvant therapy (olaparib maintenance) and family screening

  • Common mistake: Resecting without EUS-FNA tissue confirmation — always confirm malignancy histologically (AIP can mimic PDAC and responds to steroids, not surgery