Esophageal Carcinoma (EC) 🥡 Flashcards

Question

Important of Siewert classification for COJ Tumour

Answer 1

🚨**Nutritional optimization before intervention!!** Divided into: - Superficial - Advanced for N:NPC - take 72g divide by 6.25g ( 1g N = to 6.25g of protein) - then divide by the NPC calculated 1g carbohydrate: 4 kcal 1g protein : 4 kcal 1g fat: 9kcal

Answer 2

Divided into: - Endoscopic Therapy - Esophagectomy with LN dissection **Invasion no deeper than submucosa (Tis or T1, N0).** - Incidence of early esophageal cancer in Asia is ↑ due to screening program. - Most important criteria for management - accurate assessment of disease extent & risk of nodal involvement. **T1a** - Risk of LN spread - 5% **T1b** - Risk of LN spread - 16.5% **Management Strategy** - **M1** & **M2** lesion or **M3** (T1a) with no LVI - **Endoscopic resection** - **M3** (T1a) with LVI or **SM** lesions (T1b) - **Esophagectomy** - Minimally invasive esophagectomy - Radiation +/- chemotherapy

Answer 3

Aim - preserve integrity of esophagus, providing potential curative options for superficial cancers. **M1** & **M2** lesion or **M3** (**T1a**) with **no LVI** **EMR / ESD** Best result achieved with: - Type : “low-risk” disease, including macroscopic types I, IIa, IIB, and IIc mucosal lesion. - Size : ≤ 2cm (EMR), ≥ 2 cm (ESD) - Grade : histological grades G1 and G2, and/or HGD ESD may have a lower local recurrence rate. Post EMR / ESD residual dysplastic lesion can be treated with repeat procedure or procedures below. Post endoscopic treatment stenosis prophylaxis - balloon dilatation, local steroid injection, or oral steroid administration.

Answer 4

Indicated for : M3 (T1a) with LVI or SM lesions (T1b) Surgery is the mainstay treatment! Advantage: - Precise pathological staging, Permanent removal of all Barrett’s mucosa at risk - Definitive treatment without need for post-operative surveillance or salvage therapy Disadvantage - Morbidity: 30%, Mortality: 5% **Radiation +/- Chemotherapy** • No role of Neoadjuvant CRT • Neoadjuvant CRT does not improve R0 resection or survival • CRT reserve for patient unwilling or unfit for surgery. CRT > RT alone. • Combination of Platinum and Fluoropyrimidines with RT; Standard 4 cycle Cisplatin/5FU +RT. Option 6 cycles FOLFOX + RT - Considered in patient with superficial cancer with liver cirrhosis & varices in which ER or Esophagectomy are contraindicated. - Muscle invasive cancer : CCRT is standard of care

Answer 5

**T1 - T4a, N ± (**Celiac, mediastinal & supraclavicular LN - regional LN**), M0** **Stage II - III** - 30 – 40% potentially resectable at presentation. - 5-year survival 15 – 20% with surgery alone - Current guideline favors multimodal approach. • Surgery alone NOT standard; Incomplete resection observed in T3 (30%), T4 (50%) • Survival with surgery alone <20% even after R0 resection • Pre-operative CRT- more R0 resection and increase survival (Level 1A) • Combination of Platinum and Fluoropyrimidines + RT **Management** MDT & specialized unit (High Volume Centre - mortality 5%, morbidity 30%). Curative Intent – surgical resection Aim: R0 resection with **5 cm distal margin, 5 cm proximal margin** & **> 15 LN** dissected **Role of pyloroplasty** - LN dissection will sacrifice vagus nerve which ↑ risk of GOO. - Pyloroplasty ↓ risk of GOO but POMR & complication rate are similar to without pyloroplasty. **Feeding Jejunostomy** - Indicated for nutritional support pre CCRT & all patient undergoing esophagectomy. - Placement is 40cm distal to ligament of Treitz.

Answer 6

- Downstage : Improve DFS, OS - Downsize : Improve resectability ( increase pCR and R0 resection) - Neoadjuvant RT allow better tumor ischemia, contrary to post-operatively where field is hypoxic thus tumor radio resistant. - Early treatment of micro-metastasis( PSS 2024) - In cervical esophageal carcinoma, simultaneous laryngectomy is often required; therefore, preoperative chemoradiotherapy or definitive chemoradiotherapy is often undertaken in an attempt to conserve the larynx for vocal function. - Larynx-preserving surgery is indicated for patients in whom tumor has not invaded pharynx, larynx, or trachea. - For SCC, non-operative management with CCRT improve long term survival in 27% patients which is similar to patients treated with neoadjuvant CCRT & surgery. Adenocarcinoma • Meta-analysis (1A), advocate perioperative CRT with Platinum+ Fluoropyrimidines (8-9 weeks pre and post Op) • CRT > RT in histological response, R0 resection, lower LN Metastasis but not Overall Survival • Cisplatin/5FU considered standard (ACCORD 07) but recent evidence favor biweekly Oxaliplatin/5FU or Carboplatin/Paclitaxel (CROSS) due to lower toxicity (2 RCTs) • Surgery indicated even in complete response as evidence is limited on watchful waiting

Answer 7

1) **Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial** [ISRCTN93793971, DOI:10.1056/NEJMoa055531] Resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus Operable and Fit T2, T3 N ± Neoadjuvant ECF (Epirubicin, cisplatin, 5FU) x 3 → Restage (EUS + PETCT) + surgery (after 6 - 8 weeks) → (Epirubicin, cisplatin, 5FU) x 3 VS Surgery alone. - Significant Down staging and Downsizing of tumor - ↑ PFS & OS 2) Dutch- **ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS)** [Netherlands Trial Register, number NTR487, DOI:10.1016/S1470-2045(15)00040-6] 75% Adenocarcinoma, 25% SCC. Operable and Fit T2, T3 N ± Neoadjuvant CCRT (Paclitaxel + carboplatin + RT 41 Gy) x 6 + Restaging (EUS + PETCT) on 3rd cycle & after completion + surgery after 6 – 8 weeks VS Surgery alone. 🍊Radiotherapy A total radiation dose of 41.4 Gy was given in 23 fractions of 1.8 Gy each, with 5 fractions administered per week, starting on the first day of the first chemotherapy cycle. (41/23 mneumonic) 🍎Chemotherapy Carboplatin - AUC 2 mg /ml/min - Paclitaxel - 50 mg /m * On days 1, 8, 15, 22, and 29 - R0 resection higher in CCRT (92%) vs. Surgery (69%). - POMR similar. - pCR 29% CCRT - ↑ OS (50% vs 24% at 5 yrs) - ♦ Therefore CCRT + surgery is recommended for resectable T2/T3 N+/- disease. ♦ Generally preferred for esophageal Ca (SCC/AdenoCa) 3) **FLOT 4 Trial** - Trial compared neoadjuvant fluourouracil plus leucovorin, oxliplatin and docetaxel (FLOT) to ECF/ECX in patients with locally advanced junctional or gastric adenocarcinoma - 1/3 Siewert Type 1 GOJ - 1/3 Siewert Type 2/3 GOJ - 1/3 Gastric cancer *There was a significant improvement in overall survival in the FLOT cohort ( median OS: FLOT 50months, ECF/ECX 35 months) Median PFS: FLOT: 30months. ECF: 18 Months - as the result, FLOT has become the gold standard for neoadjuvant chemotherapy regime for EC and gastric ca. 4) **NEO-AEGIS Trial** - Compared perioperative chemotherapy ( n=184, 157 MAGIC, FLOT 27) with CROSS (n=178) - no significant differences in OS - improved pathological response in the radiotherapy arm did not translate into improved OS 5) 🥇LATEST Trial 2024 Prospective randomized multicenter phase III trial comparing perioperative che- motherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus **(ESOPEC trial)** - Patients with cT1 cN+ cM0 or cT2-4a cN any cM0 resectable EAC were eligible - Between Feb 2016 and Apr 2020, 438 patients from 25 sites in Germany were randomly assigned to two treatment groups (221 FLOT; 217 CROSS). - Median OS was 66 (95% CI 36 – not estimable) months in the FLOT arm, and 37 (95% CI 28 – 43) months in the CROSS arm. - In 359 patients with available tumor regression status, pathological complete response was achieved in 35 (19.3%, 95%-CI 13.9 – 25.9%) in FLOT and in 24 (13.5%, 95%-CI 8.8 – 19.4%) in CROSS. **- Conclusions: Perioperative FLOT improves survival in resectable EAC compared to neoadjuvant CROSS.** * RULE OF THUMB – JUST REMEMBER 5FU & CISPLATIN → SURGERY. PACLITAXEL ONLY IF PATIENT FIT.

Answer 8

Surgery depends on location of tumor: **Cervical Esophageal Carcinoma (SCC)** CCRT 1st line treatment. If pCR, surgery may not be needed. Treated as per head and neck SCC. - Surgery if failed CCRT - Resection of portions of pharynx, larynx, thyroid, prox esophagus & bilateral neck dissection - 1 stage & 3 phase op : Cervical, thoracic, abdominal incision with permanent trachy. **Thoracic Esophageal Carcinoma** **Total** esophagectomy indication: - For all Squamous Cell Carcinoma - Tumors located in upper & middle third esophagus regardless of histology due to risk of submucosal skip lesions. **Subtotal** esophagectomy indication: - Lower third esophageal carcinoma - COJ tumors.

Answer 9

1) **Ivor-Lewis esophagectomy** **2 stage** **subtotal** esophagectomy for **middle and lower third of esophagus**. 2) **Modified Ivor Lewis:** **Left thoracoabdominal** incision with intrathoracic anastomosis. 3) **McKeown’s (tri-incisional) esophagectomy** **3 stage** **total esophagectomy** for patients with tumors **located above the gastroesophageal junction up to level of clavicles**. 4) **Trans hiatal Esophagectomy** For tumors involving **lower third of esophagus and gastric cardia**. - **Orringer Technique** **2 stage** Trans hiatal **total esophagectomy** without thoracotomy

Answer 10

**2 stage** **subtotal** esophagectomy for **middle and lower third of esophagus**. Disadvantage : intrathoracic anastomosis, 3- 20% bile reflux. Combined laparotomy followed by Right thoracotomy with intrathoracic anastomosis. - **Laparotomy** - mobilization of stomach, mobilization of esophagus within hiatus, gastric tube created, upper abdominal lymphadenectomy with resection of the lymph nodes along celiac trunk and splenic and common hepatic arteries. Either pyloroplasty, pylorotomy, pyloromyomectomy, or botulinum toxin injected into pyloric muscle to prevent postvagotomy gastric outlet obstruction due to stasis. - **Right thoracotomy** - azygos vein divided, esophagus and its adjacent mediastinal lymphatic tissue resected en bloc (periesophageal, aortopulmonary, subcarinal, left recurrent laryngeal nerve nodal groups). Gastric tube or whole-stomach conduit is then pulled up into the chest, stomach is divided at the cardia an intrathoracic end-to-end anastomosis is created between residual esophagus and gastric conduit. This is followed by a feeding jejunostomy. Esophagogastric anastomosis is placed as high as possible in the chest, above the level of azygos vein, to achieve the best surgical margin and decrease reflux.

Answer 11

**Left thoracoabdominal** incision with intrathoracic anastomosis. - Primarily for **distal esophageal and gastroesophageal junction tumors** and provides exposure of superior abdominal and posterior mediastinal compartments through a single incision. - Extensive lymphadenectomy can be performed in abdomen and posterior mediastinum with this technique.

Answer 12

**3 stage** **total esophagectomy** for patients with tumors **located above the gastroesophageal junction up to level of clavicles**. Abd-thoracic-neck dissection with cervical anastomosis with complete upper abdomen and mediastinal lymphadenectomy (2 field) or cervical LN (3 field) dissection. Most curative, higher risk, but with better ICU care & epidural analgesia, morbidity & mortality almost the same mortality 2.5 – 10%, morbidity 24-75%, recurrence rate 1-12%. - **Right thoracotomy** - patient in left lateral decubitus position incision in fifth ICS, esophagus and all of the adjacent nodal and, as necessary, mediastinal tissues are mobilized en bloc from uninvolved healthy mediastinal structures, leaving the esophagus in continuity. After surgical drains are placed, the chest is closed. - **Midline laparotomy** - patient in supine position, stomach and adjacent lymphatic tissue are mobilized in the same manner as with Ivor Lewis technique. A gastric conduit is created by using either a whole-stomach or a gastric tube, with or without a pyloric drainage procedure. Gastric conduit with the right gastroepiploic blood supply is brought to the neck through the left cervical incision. After removal of the esophagus through either the left neck incision or the upper midline incision (depending on the size of the lesion), the cervical esophagogastric anastomosis is created followed by a feeding jejunostomy.

Answer 13

For tumors involving **lower third of esophagus and gastric cardia**. Major advantage - the potential to diminish respiratory complications by avoiding a thoracotomy and an intrathoracic anastomosis with a possible intrathoracic anastomotic leak. Disadvantages - increased rate of anastomotic leak for a cervical anastomosis, increased risk for subsequent stricture formation, and higher risk for recurrent laryngeal nerve injury. Unable to do thoracic LN dissection & blind thoracic dissection. **Orringer** **2 stage** Trans hiatal **total esophagectomy** without thoracotomy - Supraumbilical incision - allows distal esophageal dissection. - Cervical phase - incision parallel to left sternocleidomastoid muscle for dissection of proximal esophagus. - Blunt dissection of esophagus in mediastinum transhiatally by insertion of surgeon’s hand through abdominal incision. Once the entire esophagus is mobilized, cervical esophagus is transected. Next, a partial gastrectomy is performed, and the esophagus is removed via the abdominal incision. Gastric conduit is then brought up to the neck through the posterior mediastinum to create a cervical esophagogastric anastomosis.

Answer 14

**Open vs. Minimally invasive** - Benefit of MIE: Smaller incision, less blood loss, less postoperative complications, overall hospital stay, better pulmonary function - Uncertainty : - Controversy in adequacy of surgical margin and LN dissection. Long term outcome not established. **Margin** - Proximal & Distal : **SCC – total esophagectomy**, **Adenocarcinoma 5 cm margin**. - **CRM** : **Positive** margin if **cancer within 1mm of CRM**. - Positive margin has significantly higher 5-year mortality rates. **Hand sewn vs. Stapled Anastomosis** - Hand sewn (single/ double layer) vs. Stapled (circular or side to side linear) - similar anastomotic leak but **stapled has higher anastomotic stricture rate**. **Cervical vs. Thoracic Anastomosis** **Cervical** - higher leak rate (13%), but limited sepsis due to anastomosis leak and difficult to stent - ↑ RLN injury - ↓ reflux, more extensive proximal resection, - location outside RT field. **Thoracic** - Lower leak rate (7%) but leak associated with significant sepsis. - Higher risk of stricture. - leaks are more easily managed with stents - Increased pulmonary complications - Increased pain - Longer recovery

Answer 15

**Conduit choice** - Gastric > Colon > Jejunum **Reconstruction post Total Esophagectomy** **Stomach** - First choice: Ease of preparation, good blood supply, and adequate length single anastomosis. - Blood supply: Preserved right gastric and gastroepiploic blood supply. - Disadvantage: Regurgitation, reflux.

Answer 16

- **Except for T1a tumor, all should undergo LN dissection**. - **Most important prognostic factor** - 60-70% patients have LN involvement at presentation. **Lymphadenectomy Extent** - **1 field** - **mediastinal** - **2 field - mediastinal**, **upper abdominal (peri gastric)** – 15 - 20 LN Western countries - en bloc resection of the mediastinal and upper abdominal lymph nodes is considered a standard for transthoracic esophagectomy. - **3 field - mediastinal, upper abdominal (peri gastric), cervical** - 30 LN Japan/Asian 3 field Lymph node dissection is done. - Recommended LN dissection for maximum 5-year survival (Japan) - T1 : 10 LN - T2 : 20 LN - T3T4 : 30 LN

Answer 17

Non Surgical and Surgical causes: **NON SURGICAL :** **Pulmonary complications** – commonest, 20-30% - Tracheoesophageal fistula. - Lung injury - even without thoracotomy, due to elevation of inflammatory mediators in this major surgery, worsened during one lung ventilation, episodes of hypoxemia. Hypotension, increased fluid/blood replacement, inotropic support may lead to ARDS - Some studies showed reduced lung complications in non-thoracotomy approach - Atelectasis, pneumonia, postop pain control essential - Pulmonary edema - Early aspiration, might be due to damage of Vagus nerve, recurrent laryngeal, loss of cough reflex, airway protection **CVS complications** - Arrhythmias in post op day 2-4 might be a sign of leak - MI in old age **Pneumothorax or Haemothorax** **DVT** **SURGICAL :** **Chylothorax** - Clinical : Septic, whitish fluid from drain - Diagnosis : Pleural fluid analysis. - Serum CBC shows lymphocyte depletion - If only minimal fluid, can give full cream milk through NG as this will increase chyle. - Management: Conservative (50% success). Drain & NBM. - Once < 100ml/day allow feed with medium chain TG, low fat diet. - Failed (>500ml/day for 5 days or persistent leak for 2 weeks) → surgery. **RLN injuries** **Anastomotic leak** - **Esophagectomy Complications Consensus Group – classification of anastomotic leak** - Proximal, stappler line, distal - **Type I:** Local defect requiring no therapy or treated medically/with dietary modification - **Type II:** Local defect requiring interventional but not surgical therapy (e.g. interventional radiology drain, stent or bedside opening of wound) - **Type III:** Local defect requiring surgical therapy **Conduit necrosis - Esophagectomy Complications Consensus Group – classification of gastric conduit necrosis** - **Type I:** Focal conduit necrosis identified at endoscopy. - Treatment – additional monitoring or non-surgical therapy - **Type II:** Focal conduit necrosis identified at endoscopy and not associated with free leakage. - Treatment – surgical therapy not involving esophageal diversion - **Type III:** Extensive conduit necrosis. - Treatment— conduit resection with diversion **Bleeding** **Tracheal injuries & tracheoesophageal fistula** **Gastric Outlet Obstruction** **Benign Anastomotic Stricture**

Answer 18

**T4a** : Potentially resectable **T4b** : Unresectable **M1** : Peritoneal, lung, liver, bone metastasis. **Patient unfit for surgery or refuse surgery** **Aim** Symptom control : Maintain swallowing ability, pain relief, bleeding prevention Disease control : To improve PFS MDT **Disease Control** Chemotherapy is the mainstay of treatment in palliative tumor - 1st line : Platinum based regime - 2nd line : Taxane - 3rd line : Gemcitabine - CCRT is the treatment of choice in potentially resectable tumour. * SCC follow RTOG 85-01 protocol **RTOG 85-01 (Radiation Therapy Oncology Group)** ♦ Landmark study ♦ RT alone vs. CCRT (5-FU + cisplatin + RT 50Gy) ♦ CCRT ↓ LR, ↑ 5 years survival ♦ CCRT is the standard of care for patient with inoperable disease based on this study Adenocarcinoma follow CROSS protocol **CROSS trial** ♦ Neoadjuvant CCRT (Paclitaxel + carboplatin + RT 41 Gy) + surgery vs. Surgery alone ♦ Outcome R0 resection higher in CCRT vs. Surgery (92% vs. 69%). POMR similar. pCR rate 29%. CCRT ↑ OS ♦ Therefore CCRT + surgery is recommended for resectable T2/T3 N+/- disease. **♦ Paclitaxel act as radiation sensitizer. Has high response rate in metastatic disease.** -Contraindication for treatment : Size > 9cm, present of TOF.* **Trastuzumab is the 1st line therapy if HER-2 positive Adenocarcinoma (10-20%)** * Ramucirumab (2nd line) usage based on trial on gastric Adenocarcinoma (RAINBOW) * Pembrolizumab A.K.A Keytruda (3rd line agent) in Programmed Cell Death (pdl-1) positive patients with deficient MMR gene (KEYNOTE)

Answer 19

Consist of : - Relieve Dysphagia - Pain relief - Bleeding control - Tracheo-esophageal fistula Tx **Relieve Dysphagia** 1) **Endoscopic Therapy** a) **Stent** - preferred treatment for stenotic carcinoma or TOF. - Types: - SEMS (Self expandable metal stents) –nitinol (alloy of nickel & titanium). - SEPS (Self expandable plastic stents) – polyflex, Less trauma, ↓ risk of fistula. - SEBS (Self expandable biodegradable stents) – polydiaxanone. - Stent with valve : reduce reflux in COJ tumors. - Coverings - Covered – resist tumor ingrowth, ↑ migration rate. Help close TOF, leaks - Uncovered - ↑ tumor ingrowth, ↓ migration rate. - Risk : Perforation, aspiration, bleeding, tracheal compression, respiratory failure. b) **Dilatation** - Done by through the scope **balloon** or **Savory Gillard bougies**. - For temporary relieve and require repeated dilatation monthly. - Risk of perforation. c) **Tumor ablation** - **Laser** (Nd: YAG) - Laser induced fulguration of malignant tissue to restore luminal patency. - **PDT** (Photodynamic Therapy) - Photosensitizing agent with endoscopic low power laser exposure. - Easier & better tolerated than Nd: YAG - **APC** (Argon Plasma Coagulation) - Monopolar, non-contact, high frequency electrocautery using ionized electrically charged argon gas to induce tissue coagulation & tumor destruction. - Use alone or in combination with PDT 2) **Surgery** a) **Salvage Esophagectomy** - Only if R0 resection is feasible with good response to CCRT - No role in metastatic or locally advance disease in view OS < 6 months b) **Bypass procedures** - Gastro-esophagostomy proximal to tumor with colonic or jejunal bypass c) **Feeding procedures** - Feeding gastrostomy / feeding jejunostomy. Only if failed, stent. **Pain relief** - Multimodal analgesia according to **WHO step ladder** approach - **CCRT** can reduce symptoms **Bleeding** - **Endoscopy** (APC, chemical hemostasis) - **Hemostatic RT** - **Transhiatal esophagectomy** **Tracheo-esophageal fistula** - **Stenting** – covered stent.

Answer 20

- Overall prognosis is poor. Overall all SEER stages combined 20%. - 5 yrs survival - Stage 1 : > 47% - Stage 2 - 3: 25% - Stage 4: 5%

Answer 21

- Recently **CheckMate 577 Trial** demonstrated improved survival with the use of the anti-programmed death 1 (PD-1) antibody , **Nivolumab (Opdivo), a human monoclonal IgG4 antibody** in the adjuvant setting - Nivolumab is now recommended by NICE for completely resected oesophageal carcinoma in adults with residual disease in the resection specimen.

Esophageal Carcinoma (EC) 🥡 Flashcards

(49 cards)