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Q1: The two faces of oesophageal cancer (2 min)
"Compare oesophageal adenocarcinoma and squamous cell carcinoma — site, risk factors, epidemiology, trend."
- Adenocarcinoma (OAC): distal oesophagus / GOJ; Barrett's metaplasia, GORD, obesity, white males, 6th-7th decade; rising in the West; the metaplasia-dysplasia-carcinoma sequence (CDX1/CDX2).
- Squamous (OSCC): upper/middle oesophagus; alcohol, tobacco, very hot beverages, achalasia, caustic injury, nitrosamines, tylosis (Howel-Evans), Plummer-Vinson; dominant globally (oesophageal cancer belt — Central/East Asia, East Africa); generally falling in the West.
- Both present with progressive dysphagia (solids then liquids) and weight loss; diagnosed by OGD + biopsy.
Q2: The Correa cascade and H. pylori (3 min)
"Walk me through the pathogenesis of intestinal-type gastric cancer. Why is H. pylori a Class I carcinogen?"
- Correa cascade: normal mucosa -> chronic (superficial) gastritis -> atrophic gastritis -> intestinal metaplasia -> dysplasia -> invasive adenocarcinoma, over decades.
- H. pylori mechanism: CagA injected via type IV secretion system (activates SHP-2, ERK/MAPK, NF-kB); urease generates ammonia; neutrophil ROS cause DNA damage; chronic inflammation drives atrophy and mutation. Loss of parietal cells raises pH -> bacterial overgrowth -> N-nitroso compounds.
- H. pylori is an IARC Group 1 (Class I) carcinogen; attributable fraction ~89 percent of non-cardia gastric cancers; eradication interrupts the cascade — a proven population-level cancer-prevention intervention (screen-and-treat in Japan/Korea/China).
- Diffuse type is different: CDH1 (E-cadherin) loss -> discohesive signet-ring cells -> linitis plastica.
Q3: Staging and the role of laparoscopy (2 min)
"How do you stage a gastric cancer, and why is staging laparoscopy non-negotiable?"
- OGD + biopsy (diagnosis, HER2, PD-L1 CPS, MSI), CT CAP (distant mets), EUS (T and N stage), staging laparoscopy with peritoneal washout cytology.
- CT misses peritoneal disease in 10 to 30 percent of apparently resectable patients; laparoscopy detects it; positive cytology = M1, avoiding futile laparotomy and redirecting to systemic therapy.
Q4: Surgery and perioperative chemotherapy (3 min)
"Describe the surgery and the perioperative regimen for resectable gastric cancer. Name the trials."
- Surgery: total or subtotal gastrectomy with D2 lymphadenectomy (D1 + nodes along left gastric, common hepatic, splenic, coeliac arteries; at least 15 nodes). Spleen-preserving D2 is standard. Roux-en-Y reconstruction.
- Perioperative FLOT: 5-FU, leucovorin, oxaliplatin, docetaxel; 4 cycles pre + 4 cycles post. FLOT4 (Al-Batran, Lancet 2019) — median OS 50 vs 35 months vs ECF/ECX; current global standard.
- MAGIC (Cunningham, NEJM 2006) — established the principle (perioperative ECF; 5-yr survival 23 -> 36 percent).
- Intergroup 0116 (Macdonald, NEJM 2001) — adjuvant chemoradiotherapy (5-FU/leucovorin + 45 Gy) after D0/D1 resection; mainly a North American approach.
- After total gastrectomy: lifelong IM hydroxocobalamin (B12) — loss of intrinsic factor; plus iron, calcium, vitamin D; counsel on dumping syndrome and osteoporosis.
Q5: Oesophageal cancer neoadjuvant therapy (2 min)
"Name the neoadjuvant regimen for oesophageal cancer and the trial."
- CROSS (van Hagen, NEJM 2012): weekly carboplatin (AUC 2) + paclitaxel (50 mg/m²) x 5 weeks + 41.4 Gy in 23 fractions, then oesophagectomy. Improved R0 (92 percent vs 69 percent) and median OS (49 vs 24 months); benefit in both histologies.
- For squamous cancer, JCOG9907 (Ando, Ann Surg Oncol 2012) established neoadjuvant cisplatin/5-FU (CF) as standard in Japan. Cervical oesophageal SCC is treated with definitive chemoradiotherapy for organ preservation.
Q6: Advanced disease and the named metastases (2 min)
"A patient has a hard left supraclavicular node and weight loss. Discuss."
- Virchow's node (Troisier's sign) = metastatic gastric cancer via the thoracic duct; indicates Stage IV.
- Other named metastases: Sister Mary Joseph nodule (umbilical), Krukenberg tumour (ovarian signet-ring), Blumer's shelf (rectal shelf), Irish node (left axillary).
- Paraneoplastic: acanthosis nigricans, tripe palms, sign of Leser-Trélat, Trousseau syndrome.
- Advanced therapy: trastuzumab if HER2+ (ToGA, OS 13.8 vs 11.1 months); nivolumab + chemotherapy if PD-L1 CPS at least 5 (CheckMate 649); ramucirumab second line.