Colon cancer GE ROUNDS pgi chandigarh.pptx

colorectal cancer

1. Colon cancer- Acute presentation Presenter: Dr Karthik M Moderator: Dr Ishita Laroiya September 20, 2024

2. Case information: Name: Mr AJ Age/Gender: 29 years / Male Address: Bijnor , gyanpur U ttar pradesh CR no.: 202403755964 Admission no.: 2024067960 DOA : 24/08/2024 DOSx : 24/08/2024 DOD: 1/09/2024

3. Brief History Bleed Per Rectum x 6 months Pain over right lower abdomen x 4 days h/o loss of weight ( 10 kg in 8 months ) N/H/O altered bowel habits/ obstipation N/H/O tenesmus / spurious diarrhoea N/H/O feeling of a lump in abdomen/ nausea/ vomiting N/H/O abdominal distension/ Jaundice N/H/O hematemesis/ dyspepsia/ fever/ Hemoptysis

4. Past History No known comorbidities (T2DM/ HTN/ CAD/ PTB/ CVA/ hypothyroidism/ Hyperthyroidism) No Previous Surgeries N/H/O Endoscopic procedure/ blood transfusion

5. Family History: N/H/O malignancies in family Personal History: Mixed diet N/H/O substance abuse Normal bladder and bowel habits No known allergies

6. Treatment history: Presented to PGIMER in Internal Medicine and Gastroenterology, underwent cross-sectional imaging and upper and lower GI endoscopy Referred to General Surgery

7. Examination Conscious, oriented, comfortable Normal built, BMI: 23.4kg/m 2 Well hydrated Vitals PR: 110 /min , regular BP: 130/80 mmHg RR: 18/min Afebrile GPE: pallor present, no icterus/ cyanosis/ lymphadenopathy/oedema/ clubbing

8. Systemic examination Respiratory system: B/L AEE, NVBS+ CVS: WNL CNS: WNL P/A : WNL

9. Investigations Colonoscopy

10. CECT abdomen ( M-17619/24- 25/07/24)

11. Colonoscopy (22/10/2022- PGI) Seen till mid-ascending colon Ulcero -proliferative growth was seen with luminal narrowing of more than 90% Few polyps were seen in the transverse colon Rest- Normal

12. Biopsy (S-29418/2022) Adenocarcinoma- moderately differentiated

13. Colonic biopsy – Tumour arranged in glands and nests

14. Tumour cells have moderate nuclear pleomorphism, coarse chromatin and inconspicuous nucleolus

15. Blood investigations Investigation value Hemogram 8.2/7000/457K Na/K 138/5 Urea/ creatinine 22.8/0.78 AST/ALT/ALP 17.8/8.8/74 TB/CB 0.13/0.07 Total protein/ Albumin 7.3/3.75 PTI/INR 100/0.9 ApTT 30.8 CEA 9.7 CA 19-9 13.26 Viral Serology Triple negative

16. Diagnosis Ca Caecum and proximal ascending colon

17. Preoperative course The patient was planned for elective surgery. The patient developed sudden onset, diffuse, colicky pain abdomen, obstipation with abdominal tenderness and fresh per rectal bleed on . Hb drop to 6.9 gm/dl. No hemodynamic instability. 2 unit PRBC transfused. A CECT abdomen with CT angiography was undertaken.

18. Change in plan In view of the acute abdomen, the patient was planned for EL + Proceed in Emergency OT.

19. Intraoperative findings Midline laparotomy. No ascites . All visualized solid organs normal, with no peritoneal deposits. 5 x 5 cm hard mass present in long segment of ascending coon with irregular surface. Mobilization of ascending colon and hepatic flexure done.

20. The ileocolic artery and middle colic artery were identified and ligated. The right colic artery was not visualized. Distal 10 cm ileum + Caecum + Ascending colon + proximal 2/3 of transverse colon resected. Side-to-side ileocolic anastomosis (distal ileum- transverse colon) was performed with continuous PDS 4-O followed by interupted sutures with PDS 4-0. The sheath was closed with a PDS loop, skin was closed with staplers.

21. Postoperative course POD 1- RT and PUC removed, orally liquid allowed. Ambulated. POD 2- c/o abdominal pain, relieved with antispasmodics, midline wound healthy. POD 3- orally fully allowed and tolerating. POD 4- Passed stool and flatus. Wound healthy. POD 5- Discharged.

22. Histopathology (S-33128/2022) Tumour site: caecum and ascending colon Tumour type: Moderately differentiated Adenocarcinoma Invasion: upto muscularis propria LVI and PNI : absent Margins: free of tumour Lymph nodes: 1/16, all free of tumor Pathological stage: pT3N1Mx

23. Tumour arranged in glandular pattern with areas of necrosis

24. Tumor cells have moderate nuclear pleomorphism, round to oval nuclei, coarse chromatin and conspicuous nucleolus

25. Lymph nodes – are free of tumour (0/7)

26. Resection margins are free of tumour

27. Follow up The patient is doing well and under follow-up under general surgery and radiotherapy. Planned for adjuvant chemotherapy due to high-risk feature- bowel obstruction, >1 lymph nodes harvested .

28. Points of discussion Emergency presentation Difference between right and left-sided colonic cancers Diagnostic workup in emergency Surgery in acute presentation Role of molecular analysis in colon cancer Role of adjuvant and neoadjuvant chemotherapy Follow up

29. Emergency presentation Nearly 8-40% of colonic cancers present as GI emergency Emergency presentations: Large bowel obstruction in 80% (15-30% of all CRC) Perforation with or without peritonitis (1-10% of all CRC) Hemorrhage Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

30. Obstructive presentation 75% of tumors located distal to splenic flexure Sigmoid colon- most common site Perforation due to CRC At the tumor site- 70% Proximal to the tumor- 30% Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

31. Emergency vs Elective More physiological derangements at presentation (dehydration/ deranged comorbidities/ poor nutrition/ shock) Worse tumor biology: rapid progression, increased T stage, LVI and PN spread, metastasis Increased rate of emergency interventions- surgery vs stenting Oncological resections vs palliative diversion Higher rates of morbidity, mortality and stoma formation Baer et al, emergency presentation of colorectal cancer, Surg Clin N Am 97 (2017) 529–545

32. Distribution of large bowel cancers Bailey and love’s short practice of surgery, ed 28 chapter 77, page 1359

33. Location- Right vs Left Right-sided CRC (RCRC) tumors- ascending colon, and proximal two thirds of the transverse colon Left-sided CRC (LCRC) tumors -the descending and sigmoid colon, and distal one third of the transverse colon Baran et al, Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review of Literature, Gastroenterol Res. 2018;11(4):264-273

34. Presentation of RCRC Baran et al, Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review of Literature, Gastroenterol Res. 2018;11(4):264-273 Advanced and bigger tumors Anemia due to occult bleed Lump in right lower abdomen Large lumen and liquid contents- obstruction rare

35. Presentation of LCRC Relatively early presentation Small caliber with solid contents  Altered bowel habits- progressive constipation LGI bleeding- hematochezia Baran et al, Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review of Literature, Gastroenterol Res. 2018;11(4):264-273

36. Differences: Right vs Left colonic cancer Right side Colon cancer Left side Colon cancer Older age Younger age Predominantly occur in female Predominantly occur in male Mucinous adenomas, sessile serrated adenomas Tubulous/ villous/ Tubulo-villous adenomas Flat morphology Polypoidal morphology MSI-H and dMMR tumors CIN high tumors Highly immunogenic, rich T cell infiltration Low immunogenic Metastasis in peritoneal region Liver and lung metastasis Better prognosis in early stages (I and II) Better prognosis at late stages (III and IV) Respond well to immunotherapy Respond well to adjuvant therapy i.e. standard cytotoxic chemotherapy and targeted therapy Baran et al, Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review of Literature, Gastroenterol Res. 2018;11(4):264-273

37. Hereditary cancer syndromes All hereditary cancer syndromes - more common on right side Exception: FAP syndrome Baran et al, Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review of Literature, Gastroenterol Res. 2018;11(4):264-273

38. Differences: Outcomes Stage II and III CRC - Patient with RCRC had more advanced disease 5 year DFS was significantly superior in RCRC (83.9% vas 81.1%) 5 year cancer specific survival in those with recurrence significantly inferior in RCRC (30.6% vs 43.6%) Ishihara et al, Impact of Primary Tumor Location on Postoperative Recurrence and Subsequent Prognosis in Nonmetastatic Colon Cancers, Ann Surg, 2018;267(5): 917-921.

39. Differences: Outcomes Metastatic CRC: Overall survival with liver metastasis 47.4 months in RCRC vs 63 months in LCRC Earlier recurrence following resection in RCRC (24.8 months vs 35.9 months) Sasaki et al, The prognostic implications of primary colorectal tumor location on recurrence and overall survival in patients undergoing resection for colorectal liver metastasis. J Surg Oncol. 2016;114(7):803- 809.

40. Diagnosis in emergency If clinical suspicion of colonic obstruction CT >>USG> AXR (modality of choice) If CT unavailable, water soluble colonic contrast enema If clinical suspicion of colonic perforation CT >> AXR or USG (modality of choice) Clear signs of diffuse peritonitis, CT scan should not delay the appropriate treatment If patient is stable and SEMS is being considered- colonoscopy CT thorax is not strictly recommended No specific data regarding staging pathways of CRC presenting as emergency Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

41. Surgery in Emergency CRC presentation A patient should be considered unstable , if any one positive: pH <7.2 Core temperature < 35 °C BE < − 8 Laboratory/clinical evidence of coagulopathy Any signs of sepsis/septic shock, including the necessity of inotropic support Damage control – start ASAP, after resuscitation If the patient is unstable, delay definitive treatment Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

42. Right sided colon cancer in emergency Obstruction Right colectomy with terminal ileostomy- procedure of choice Severely unstable patients - loop ileostomy Perforation Right colectomy with terminal ileostomy – procedure of choice If open abdomen considered- delay stoma formation Right colectomy with ileo-colic anastomosis – look nutrition, hemodynamic stability, OT time and bowel vascularization Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

43. If unresectable: Side to side ileo-transverse anastomosis can be performed Loop ileostomy NO ROLE OF DECOMPRESSIVE CECOSTOMY SEMS Bridge to elective surgery- not recommended unless very high risk patient Palliation Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

44. Left sided colon cancer in emergency Obstruction Hartmann’s procedure- procedure of choice Severe hemodynamic instability- loop transverse colostomy Perforation Hartmann’s procedure- procedure of choice If open abdomen is considered- stoma formation should be delayed Resection and primary anastomosis- if no other risk factors, no evidence to support diverting stoma Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

45. Total colectomy vs segmental colectomy- bowel ischemia/ Caecal tears or multiple perforations/ synchronous right colonic cancers Intraoperative colonic irrigation/ manual decompression- surgeon and center preference Laparoscopy- not recommended (reserved for highly selected cases) Palliative SEMS Bridge to surgery SEMS vs tube decompression Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

46. Open abdomen Can be considered if- Risk of compartment syndrome after surgery Bowel viability questionable No clear indications in peritonitis Should be closed within 7 days Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

47. Continue intraoperative resuscitation Communication is essential Always coordinate with anesthesiologist Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36 Intraoperative resuscitation

48. Antibiotic prophylaxis Gram negative bacilli + anaerobic bacteria Recommended in colorectal carcinoma obstruction and no systemic signs of infection or perforations Should be discontinued after 24 h (or 3 doses) If unstable- broad spectrum antibiotic Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

49. Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

50. Pisano et al, 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation, World Journal of Emergency Surgery (2018) 13:36

51. Role of molecular analysis in colon cancer Why molecular analysis? Choice of systemic therapy Prognosis evaluation Integral component of CRC management NCCN Guidelines Version 3.2022 Colon Cancer

52. Biomarkers for systemic therapy Microsatellite instability (MSI) Deficiency of mismatch repair gene ( dMMR )- MSI-H For use of adjuvant therapy in stage II disease More common in stage II disease than in stage III disease Less metastasis 5-FU chemotherapy is detrimental in dMMR stage II disease, but not in stage III disease NCCN Guidelines Version 3.2022 Colon Cancer

53. Prognostic but not predictive of the benefit or detrimental impact of adjuvant therapy in stage II Should be evaluated in every patient with a history of CRC In stage IV disease – 3.5-6% dMMR status Marker of immunogenicity Immune evasion mechanism Sensitive to PD-1 inhibitors (Pembrolizumab, Nivolumab, and Ipilimumab) NCCN Guidelines Version 3.2022 Colon Cancer

54. Bernhard M et al, Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability Author links open overlay panel, Immunity, 2016:44;698-711

55. Other Biomarkers KRAS and NRAS mutation BRAF V600E mutation HER 2 amplification/ overexpression NTRK gene fusions NCCN Guidelines Version 3.2022 Colon Cancer

56. Other prognosis evaluation modalities Multigene assays Oncotype DX ColoPrint ColDx Immunoscore ctDNA NCCN Guidelines Version 3.2022 Colon Cancer

57. Adjuvant chemotherapy- Indications Can be considered in stage II disease- if MSS or pMMR with any risk Mandatory in stage II disease with high risk for recurrence T4 tumors (IIB/IIC) Poorly differentiated or undifferentiated histology LVI/ PNI Tumor budding Bowel obstruction/ localized perforation Close/ indeterminate or positive margins Inadequately sampled nodes (<12 LN) Stage III disease or above NCCN Guidelines Version 3.2022 Colon Cancer

58. Timing of chemotherapy Each 4-week delay in chemotherapy results in a 14% decrease in OS Risk factors for delayed chemotherapy More likely to be older than 65 years An emergency resection A prolonged postoperative admission NCCN Guidelines Version 3.2022 Colon Cancer

59. Duration of adjuvant therapy 3 months vs 6 months- FOLFOX/CAPEOX Neurotoxicity severity rates - lower in the 3 months vs 6 months treatment Diarrhea rates - lower with the shorter duration of therapy NCCN Guidelines Version 3.2022 Colon Cancer

60. Choice of therapy “ The current definition of high-risk stage II colon cancer is clearly inadequate, because many patients with high-risk features do not have a recurrence while some patients deemed to be average-risk do.” NCCN Guidelines Version 3.2022 Colon Cancer

61. High risk stage II disease 6 months regimen 5-FU/LV Capecitabine FOLFOX Observation can be considered NCCN Guidelines Version 3.2022 Colon Cancer

62. Tumor with T1-3, N1 3 months regimen- CAPEOX 3 or 6 months- FOLFOX 6 months capecitabine or 5-FU/LV, where oxaliplatin therapy is believed to be inappropriate NCCN Guidelines Version 3.2022 Colon Cancer Low-risk stage III disease

63. High risk stage III disease Tumors with T4, N1-2 or any T, N2 6 months FOLFOX 3 to 6 months CAPEOX 6 months capecitabine or 5-FU/LV, where oxaliplatin therapy is believed to be inappropriate NCCN Guidelines Version 3.2022 Colon Cancer

64. Adjuvant therapy in elderly Safety not well established by trials Oxaliplatin addition to adjuvant therapy: Small, non-significant benefit Reduced benefit over 70 years of age Benefit and toxicities of 5-FU/LV as adjuvant therapy -similar in older and younger patients NCCN Guidelines Version 3.2022 Colon Cancer

65. Perioperative chemoradiation May be considered for very select patients T4 tumours penetrating a fixed structure Patients with recurrent disease Locally unresectable disease Medically inoperable NCCN Guidelines Version 3.2022 Colon Cancer

66. Neoadjuvant Therapy FOLFOX and CAPEOX- may be considered Relative indications: Bulky nodal disease Clinical T4b FOxTROT trial Showed significant downstaging Histologic regression- 59% Pathological complete response- 4% NCCN Guidelines Version 3.2022 Colon Cancer

67. Posttreatment Surveillance Why? To evaluate for possible therapeutic complications Discover recurrence and potentially resectable cure Identify metachronous neoplasms at a preinvasive stage 80% recurrence- within 3 years of surgical resection of the primary tumour 95% recurrence- within 5 years of primary resection Controversial data from different studies about optimal strategy NCCN Guidelines Version 3.2022 Colon Cancer

68. Modalities for Posttreatment Surveillance Surveillance colonoscopy Metachronous polyps- the most risk of developing second cancer in the first 2 years of resection Increased frequency for patients with Lynch syndrome CT scan (chest + abdomen + pelvis) Monitor for potentially resectable metastasis- liver, lung NCCN Guidelines Version 3.2022 Colon Cancer

69. Stage I disease Less intensive Colonoscopy after 1 year of surgery Repeat colonoscopy at 3 years and then every 5 years If an advanced adenoma is found at any colonoscopy- repeat at 1 year Advanced adenoma- Villous polyp, >1 cm polyp, High-grade dysplasia CEA- no recommendation at present NCCN Guidelines Version 3.2022 Colon Cancer

70. Stage II/III disease History and physical examination Every 3-6 months for the first 2 years Then, every 6 months for a total of 5 years CEA Compare to baseline Every 3-6 months for the first 2 years Then, every 6 months for a total of 5 years NCCN Guidelines Version 3.2022 Colon Cancer

71. Colonoscopy At 1 year after resection- if a complete colonoscopy was done before surgery At 3-6 months after surgery- if a complete colonoscopy was not done before surgery because of obstructing lesion Repeat colonoscopy at 3 years and then every 5 years If an advanced adenoma is found at any colonoscopy- repeat at 1 year More frequent colonoscopy- if colon cancer before 50 years of age NCCN Guidelines Version 3.2022 Colon Cancer

72. Contrast-enhanced CT chest+ abdomen+ pelvis Every 6-12 months for 5 years in stage III and high-risk stage II disease Routine CEA and CT scanning are not recommended beyond 5 years Use of PET/CT - not recommended NCCN Guidelines Version 3.2022 Colon Cancer

73. Increasing CEA levels Physical examination Colonoscopy CECT chest + abdomen + pelvis Consider PET/CT If imaging studies are normal with rising CEA- repeat CT every 3 months until either disease is identified or CEA level stabilises NCCN Guidelines Version 3.2022 Colon Cancer

74. Take home message Colonic cancer can present in emergency Such patients can have deranged physiology and hemodynamic instability High likelihood of poor outcomes than their electively managed counterparts Resuscitation is the key Surgical management -adhere to oncological principles, permitting the patient’s condition Bailout procedures -if poor patient status High chance of delay in adjuvant therapy

75. THANK YOU