Gastro 51 Sporadic colorectal carcinoma

• Age usually  >50  years of age.
• 20% of cases present as an emergency with intestinal obstruction or peritonitis.
• Right colon mass - 3 A (Anemia, asthenia and anorexia), pain abdomen, hard mass in RIF, and no features of obstruction.
• Left colon - Progressive constipation and change of bowel habits, Spurious diarrhea, Acute, sub acute or chronic large bowel obstruction, Bleeding per rectum, Mass is rare 
• An emergency presentation of colorectal cancer is, even when matched for disease stage, associated with a considerably worse prognosis.

[Note - 3 A in stomach cancer is also the same - Anemia, asthenia and anorexia]

• Double-contrast barium enema shows a cancer of the colon as a constant irregular filling defect often described as looking like an apple core.
• CT is used as a diagnostic tool in patients with palpable abdominal masses.
• Use of spiral CT of the chest and abdomen is now standard to stage colonic cancer by assessing T stage and detecting metastases. CT virtual colonoscopy - effective in picking up polyps down to 6 mm, advantage of being less invasive than colonoscopy, but if a biopsy is required, an endoscopy will still be needed.

• Tis -  intraepithelial or invasion of lamina propria
• T1 - submucosa
• T2 - muscularis propria
• T3 - pericolorectal tissues
• T4a - Tumor penetrates to the surface of the visceral peritoneum
• T4b - Tumor directly invades or is adherent to other organs or structures

• N1- 1-3 nodes
• N2 - ≥ 4 nodes

• Histologic Grade (G)
• G1 Well differentiated
• G2 Moderately differentiated
• G3 Poorly differentiated
• G4 Undifferentiated

• I – T1,T2
• II – T3, T4
• III – Node Positive
• IV – Metastasis

•  A, Invasion of but not breaching the muscularis propria
•  B, Breaching the muscularis propria but not involving lymph nodes
•  C, Lymph nodes involved
•  Dukes himself never described a stage D, but this is often used to describe metastatic disease

[@ Stage I, II, III and IV is Dukes A, B, C and D respectively]

• cTNM – Clinical stage
• pTNM – Pathological stage
• ypTNM – Pathological stage after preoperative chemotherapy

• Synchronous adenocarcinomas
• - Detected either pre / intraoperatively, or in a 6 month period postoperatively.
• - Distinctly separate by at least 4 cm distance and they should not consist of submucosal spread or a satellite lesion of each other. In any other case they are considered as regional spread or metastatic lesions.

• Metachronous carcinomas -
• - Diagnosed 6 months after the operation for the primary lesion
• - Located in a different part of the large intestine, so as to not represent a recurrence.

• Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion.
• CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Therefore, CEA is usually present only at very low levels in the blood of healthy adults.

While handling the tumor there is some chance of dissemination of the tumor cells by the blood-stream. Early division of blood vessel before the tumor is handled can reduce the chance of dissemination of tumor cells by the bloodstream during handling of the tumor. before the tumor is handled the blood vessel draining the site of growth is ligated. This is called Turnbull no touch technique of colonic resection.

Ileocolic Resection (Right limited hemicolectomy) - a limited resection of the terminal ileum, cecum, and appendix. It is used to remove disease involving these segments of the intestine (e.g., ileocecal Crohn’s disease) and benign lesions or incurable cancers arising in the terminal ileum, cecum, and, occasionally, the appendix

Right hemicolectomy - The ileocolic vessels, right colic vessels, and right branches of the middle colic vessels are ligated and divided. Approximately 10 cm of terminal ileum are usually included in the resection. The artery are ligated close to their origin off the superior mesenteric artery (‘high-tie’) and divided. 

Extended right hemicolectomy – An extended right colectomy includes the resection of the distal transverse colon and sometimes the splenic flexure, and involves ligating the ileocolic, right colic, and middle colic vessels at their base.

Left hemicolectomy – The left branches of the middle colic vessels, the left colic vessels, and the first branches of the sigmoid vessels are ligated. Resection of splenic flexure and rectosigmoid junction (avoid incorporating the proximal sigmoid colon into the anastomosis – tenuous blood supply from IMA and frequent involvement of sigmoid colon and diverticular diseases.

Extended Left hemicolectomy - the left colectomy is extended proximally to include the right branches of the middle colic vessels

Sigmoid Colectomy - Lesions in the sigmoid colon require ligation and division of the sigmoid branches of the inferior mesenteric artery. 

Total Proctocolectomy - entire colon, rectum, and anus are removed and the ileum is brought to the skin as a Brooke ileostomy.

Restorative Proctocolectomy (Ileal Pouch–Anal Anastomosis) - The entire colon and rectum are resected, but the anal sphincter muscles and a variable portion of the distal anal canal are preserved. Bowel continuity is restored by anastomosis of an ileal reservoir to the anal canal.

Anterior Resection - resection of the rectum from an abdominal approach to the pelvis with no need for a perineal, sacral, or other incision. Three types of anterior resection have been described.

• High Anterior Resection
• - resection of the distal sigmoid colon and upper rectum
• - appropriate operation for benign lesions and disease at the rectosigmoid junction such as diverticulitis.
• - Pelvic peritoneum is not divided and the rectum is not mobilized fully from the concavity of the sacrum.

• Low Anterior Resection
• - A low anterior resection is used to remove lesions in the upper and mid rectum.
• - Pelvic peritoneum is opened.
• - The rectum is mobilized from the sacrum. The dissection may be performed distally to the anorectal ring, extending posteriorly through the rectosacral fascia to the coccyx and anteriorly through Denonvilliers’ fascia to the vagina in women or the seminal vesicles and prostate in men.
• - A low rectal anastomosis usually requires mobilization of the splenic flexure

• Extended Low Anterior Resection
• - To remove lesions in the distal rectum (but away from sphincter)
• - The rectum is fully mobilized to the level of the levator ani muscle just as for a low anterior resection, but the anterior dissection is extended along the rectovaginal septum in women and distal to the seminal vesicles and prostate in men.

• Cancer located at the hepatic flexure to the mid-transverse colon
• Synchronous ascending and transverse colon cancers
• Multiple adenomas, which may or may not be part of a genetic syndrome

• Injury to critical structures 
• - Injury to the ureter or gonadal vessels
• - Injury to the duodenum in right, spleen in left
• - Venous bleeding 
• - Inadvertent ligation of the superior mesenteric artery
• - Excessive tension on the anastomosis 

• Anastomotic leak
• Abdominopelvic abscess
• Fistula
• Hemorrhage
• Bowel obstruction
• Wound infection
• Complications of general anesthesia

• Right hemicolectomy - Increase in stool volume (around 750-1000ml ), frequency is almost normal  
• Left hemicolectomy - increase in stool frequency, but volume is almost  same (250ml)
• Total colectomy - increase in stool volume and frequency

Removal of entire colon from ileum to rectum

• Colonoscopy after one year – if polyp are detected, remove polyp and repeat colonoscopy every year until the examination reveals absence of polyp. Then colonoscopy to be done every 5 years unless strong family history or genetic risk.
• CEA – every 3 months for first 2 years, even if preoperative CEA was normal

• 5-FU based adjuvant chemotherapy with at least one poor prognostic indicator
• - Insufficient LN sampling (<12 nodes)
• - T4 lesion
• - Poorly differentiated histology
• - Bowel perforation

• CEA every 3 months for 2 years, then every 6 months for total 5 years
• Annual CT scan of abdomen and chest for at least 3 years

• FOLFOX regimen. 
• FOL– Folinic acid (leucovorin)
• F – Fluorouracil (5-FU)
• OX – Oxaliplatin (Eloxatin)

FOLFIRINOX regimen, which is used in metastatic pancreatic cancer is not effective in colon cancer. Irinotecan (Camptosar) is not used.

Adjuvant treatment in patients with stage III colon cancer is recommended for 12 cycles, every 2 weeks. The recommended dose schedule given every two weeks is as follows:

• 
• 

• Continous infusion – superior
• Bolus infusion

For asymptomatic patients - a chemotherapy first approach is often used. It allows the patient to benefit immediately from systemic therapy without a waiting period for healing after surgery. Most patients with asymptomatic stage IV disease do not benefit from removal of the primary lesion. Hepatic or pulmonary lesions may be amenable to resection, typically after three to six cycles of chemotherapy and then reimaging to determine response.

Agents complementing the 5-FU regimens that remain the key stone of therapy are effective for metastatic disease. These are the monoclonal antibodies bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix).

„ Single hepatic metastasis or multiple metastasis confined to one lobe/segment: may be resected during primary surgery

„ Multiple painful hepatic metastases to both lobes - palliative treatment

• Right colonic growth - ileotransverse anastomosis
• Left colonic growth - transverse colostomy
• Sigmoid or rectal growth - sigmoid colostomy proximal to the growth

For patients who have undergone potentially curative resection of a colon cancer, postoperative (adjuvant) chemotherapy eradicates micrometastases, reduces the likelihood of disease recurrence, and increases cure rates. The benefits have been most clearly demonstrated in patients with stage III (node-positive) disease. In this setting, a six-month course of oxaliplatin-based chemotherapy is generally recommended. The benefit of chemotherapy for resected stage II disease is controversial, and treatment decisions must be individualized. Whether oxaliplatin-based regimens should be used in stage II disease in addition to 5-FU–leucovorin is controversial, but current practice in most areas appears to favor the addition of oxaliplatin in early-stage disease

Most patients who present with metastatic disease are not surgical candidates, and palliative chemotherapy is generally recommended. However, surgery may provide a potentially curative option for selected patients with limited metastatic disease, predominantly in liver and lung. An aggressive surgical approach to both the primary and the metastatic sites is warranted in such patients, in conjunction with systemic chemotherapy. For patients with unresectable distant metastases, the overwhelming majority of patients without symptoms who initiate chemotherapy never require palliative surgery.

• The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR)
• The ErbB protein family consists of 4 members
• ErbB-1, also named epidermal growth factor receptor (EGFR)
• ErbB-2, also named HER2 in humans and neu in rodents
• ErbB-3, also named HER3
• ErbB-4, also named HER4

• Lung cancer - gefitinib, erlotinib, afatinib, brigatinib and icotinib
• Colon cancer – cetuximab
• Recent EGFR inhibitor - Osimertinib

• Cetuximab is a chimeric (mouse-human) monoclonal antibody; panitumumab, a fully human monoclonal antibody, binds to and inhibits the EGFR, which is overexpressed in 60% to 80% of colorectal cancers and is associated with a shorter survival time.
• Cetuximab and panitumumab are effective only on tumors that do not have a mutation of the KRAS gene.
• Accordingly, genetic testing is now recommended to confirm the absence of KRAS mutations (indicating the presence of the KRAS wild-type gene) before the use of these EGFR inhibitors is recommended.

EGFR blockers are effective only on the tumors that do not have a mutation of K-ras gene. Genetic testing is now recommended to confirm the absence of K-ras mutation (indicating the presence of K-ras wild type gene) before the use of EGFR inhibitors.

Large bowel can tolerate properly delivered radiation dose upto 6000cGy whereas such level of radiation targeted to colon tumors would include small bowel in treatment field. The small bowel cannot withstand radiation dose of this level without complication of radiation – radiation enteritis, stricture, hemorrhage, perforation

A benign solitary ulcer in rectal mucosa because of trauma from recurrent intussuception, that can be confused with invasive adenocarcinoma. Also called as solitary rectal ulcer or Internal rectal intussuception.

Bleeding - This is often bright red in colour but may be darker, and should be carefully investigated at any age.

Altered bowel habit - Early-morning stool frequency (‘spurious diarrhoea’) is a symptom of rectal carcinoma, while blood-stained frequent loose stools characterise the inflammatory diseases.

Discharge - Mucus and pus are associated with rectal pathology.

Tenesmus - Often described by the patient as ‘I feel I want to go, but nothing happens’, this is normally an ominous symptom of rectal cancer, but can occur with any rectal pathology.

Prolapse - This usually indicates either mucosal or full-thickness rectal wall descent.

Loss of weight - This usually indicates serious or advanced disease, e.g. hepatic metastases.

• The goal of the pretreatment staging evaluation is to assess the presence of distant metastatic disease, and to determine the tumor location in the rectum and its local extent.
• An accurate assessment of location and local tumor extent is necessary prior to treatment in order to select the surgical approach and to identify those patients who are candidates for initial therapy (chemoradiotherapy, radiotherapy alone, or a combination of chemotherapy and chemoradiotherapy) prior to surgery.

• 1. Physical and endoscopic examination
• - Digital rectal examination (DRE) - fixation of the lesion to the anal sphincter, its relationship to the anorectal ring, and fixation to both the rectal wall and the pelvic wall muscles (levators) can be assessed. Superficially invasive tumor are mobile. Increasing depth of penetration leads to  tethered and fixed mass. 
• - Proctoscopy - determine the distance between the distal tumor margin, the top of the anorectal ring, and the dentate line.
• - Colonoscopy

• 2. Imaging
• - Local imaging — Thin-cut MRI with pelvic phased-array coil/endorectal coil is the preferred imaging modality for evaluating the extent of the primary tumor as it will be able to provide information on the circumferential resection margin (CRM), as well as invasion to other organs and structures. CT is less helpful in predicting local tumor resectability
• - Evaluation for distant metastases —contrast-enhanced CT scan of the chest, abdomen, and pelvis is recommended for all patients with a new diagnosis of invasive rectal cancer

3. Tumor markers - Serum levels of CEA have prognostic utility in patients with newly diagnosed colorectal cancer. Elevated preoperative CEA levels that do not normalize following surgical resection imply the presence of persistent disease and the need for further evaluation.

4. TNM staging

• 

1. Tumors in the upper and middle rectum - low anterior resection (LAR), coloanal anastomosis, and preservation of the anal sphincter

2. Tumor in the lower rectum (ie, tumors within 5 cm of the anal verge ) - Abdominoperineal resection (APR)

3. Sphincter-sparing approaches for lower rectal tumor have evolved along two pathways:

• ● Small rectal adenocarcinomas that are superficial and confined to the rectal wall - Transanal local excision by either transanal endoscopic microsurgery or fulguration.
• ● Larger or more invasive tumors - preoperative (neoadjuvant) radiotherapy (RT) and chemoradiotherapy to promote tumor regression in an attempt to convert a planned APR to a sphincter-sparing surgical procedure.

• Mobile tumor <3cm in diameter
• <30% of rectal wall circumference
• Located in distal rectum
• Well or moderately differentiated histologically
• No vascular invasion /Lymphatic invasion
• No evidence of nodal disease in pre-op USG or MRI

• 4-cm diameter procotoscope
• Four functions – CO2 insufflator, water irrigation, suction , monitoring of intrarectal pressure
• It is a closed and sealed device – rectum distends when CO2 is insufflated – facilitates visualization
• Advantage – excellent exposure

Cannot provide the specimen to access the pathological stage because the tumor margin are disintegrated by fulguration

• Definitive indication
• - Stage II/III disease

• Relative indications
• - a distal rectal tumor for which an APR is thought to be necessary
• - If the preoperative staging evaluation suggests the presence of tumor invading or in close proximity (within 2 mm) of the mesorectum because of the decreased likelihood of achieving a tumor-free circumferential resection margin

Short-course RT (25 Gy in five fractions over one week) followed by LAR or APR  - followed in Europe

Long course Chemoradiotherapy

• - 4500-5040 cGy of radiation in conjunction of 5-FU based chemotherapy or oral Capecitabine.
• - Continuous infusion fluorouracil is preferred during the entire course of RT. Oral capecitabine  is an appropriate alternative. 
• - Radiation is delivered during a period of 5-6 weeks and surgery is done 6-10 weeks after completion of radiotherapy. This course is followed in USA.

Surgical resection remains the standard approach after neoadjuvant therapy even if they appear to have a complete clinical response (cCR) to induction therapy.

Surgical resection within 7 to 10 weeks after the completion of chemoradiotherapy. A diverting stoma is made to protect anastomosis, closed 10 weeks later.

All patients who undergo neoadjuvant chemoradiotherapy should receive four months of adjuvant chemotherapy, regardless of the pathologic findings.

• 1. Negative distal margin
• - cancers located above the distal mesorectal margin ≥ 2 cm
• - cancers located at or below the distal mesorectal margin ≥ 1
• - Failure to achieve an adequate distal margin mandates conversion to an APR 

2. Negative proximal margin of 5 cm

3. Negative circumferential radial margins > 1 mm

4. Total mesorectal excision rather than a blunt dissection.

5. Lymph node dissection – up to the level of the origin of the superior rectal artery. "High" ligation of the inferior mesenteric artery at the origin of the aorta or extended lymph node dissection laterally is not necessary in the absence of clinically positive nodes. A benchmark of 12 lymph nodes has been adopted as a quality metric for colorectal cancer surgery by several societies.

• Also called as Miles procedure, named after Ernest Miles 
• Complete exicision of rectum and anus by concomitant dissection through the abdomen and perineum with suture of perineum and creation of permanent colostomy.
• Pelvic dissection is carried upto levator ani muscle
• Perineal dissection – excision of anus and sphinchers and distal rectum
• Prone position has better outcome

• Tumor involves the anal sphincter or too close to sphincher (tumors within 5 cm of the anal verge) for adequate margin to be obtained.
• Sphincter preserving surgery not possible – unfavorable body habitus or poor pre-operative sphincter control

Resection of rectum below the peritoneum reflection through the abdominal approach. Sigmoid colon is almost always included. Intestinal continuity re-established between descending colon and rectum by circular stapling devices. Temporary ileostomy as required – close after 10 weeks

Frequent small bowel movement due to loss of normal rectal capacity.

• Fashioning a colon J-Pouch as a proximal component of anastomosis
• Coloplasy

• In obese patients or patients with narrow pelvis, a bulk of J-pouch will not fit on narrow pelvis. In such cases, a reservoir can be devised with coloplasty.
• Coloplasty is performed by making 8-10 cm colostomy 4-6 cm from the cut end of colon. A longitudinal colostomy is made between the tenia on the antimesenteric side. It is closed transversely with absorbable suture. An end-end stapled anastomosis then joins the colon to the distal rectum or anus.

Preoperative chemo-radiotherapy – shrink tumor to an extent that acceptable margin can be achieved – colorectal anastomosis.

Lloyd-Davies position is common position for surgical procedures involving the pelvis and lower abdomen. The majority of colorectal and pelvic surgery is conducted with the patient in the Lloyd-Davies position.

It is also known as the Trendelenburg position with legs apart. The basic angle is a 30-degree Trendelenburg with the hips flexed at 15 degrees; this can be adjusted with leg supports.

• Standard transabdominal TME — Standard TME is performed transabdominally with open, laparoscopic, or robotic techniques. A standard TME for rectal cancer includes
• (1) high ligation of the inferior mesenteric artery (IMA),
• (2) complete mobilization of the splenic flexure,
• (3) division of the colon at the descending sigmoid junction,
• (4) sharp dissection in the avascular plane into the pelvis anterior the presacral fascia and outside the fascia propria or enveloping visceral fascia,
• (5) division of lymphatic and middle hemorrhoidal vessels anterolaterally, and
• (6) inclusion of all pelvic fat and lymphatic material at least 2 cm below the level of the distal margin.

Transanal TME - for distal rectal tumors in obese male patients with a narrow pelvis

• - The local recurrence rates of an APR or sphincter-sparing procedure with TME is significantly low with and better survival
• -  decreased postoperative genitourinary dysfunction due to pelvic autonomic nerve preservation.

A midline incision is made starting just above the symphysis taking the incision up to the right of umbilicus to about 5 cm above the umbilicus. 

Steps of TME

Perineal incision: An elliptical incision is made around the anal orifice and the incision is extended anteriorly 3–4 cm from the anal verge and posteriorly the incision is extended up to the tip of the coccyx.

The incision is deepened into the perirectal fat up to the pelvic diaphragm (Levator ani). The anterior and posterior branches of inferior hemorrhoidal vessels which runs in the ischiorectal fossa below the levator ani are coagulated and divided.

• ● Endoluminal stenting — Stenting should not be performed for distal rectal cancer, because stents deployed in the low rectum can cause tenesmus and pain.
• ●Proximal diversion — to relieve intestinal obstruction
• ●Fulguration .
• ●Endocavitary radiation by contact and/or interstitial brachytherapy

It is an artificial opening made in the colon to the exterior (skin) to divert faeces and flatus.

1. Temporary: Is done in conditions wherein diversion is required to facilitate healing distally in the rectum or distal colon. And this is closed once the purpose is over. It can be loop colostomy or Devine’s double-barrel colostomy.

2. Permanent colostomy is always end colostomy placed in left iliac fossa, 6 cm above and medial to the anterior superior iliac spine.

• ■ May be colostomy or ileostomy
• ■ May be temporary or permanent
• ■ Temporary or defunctioning stomas are usually fashioned as loop stomas
• ■ An ileostomy is spouted; a colostomy is flush
• ■ Ileostomy effluent is usually liquid whereas colostomy effluent is usually solid
• ■ Ileostomy patients are more likely to develop fluid andelectrolyte problems
• ■ An ileostomy is usually sited in the right iliac fossa
• ■ A temporary colostomy may be transverse and sited in the right upper quadrant
• ■ End-colostomy is usually sited in the left iliac fossa
• ■ All patients should be counselled by a stoma care nurse before operation
• ■ Complications include skin irritation, prolapse, retraction,necrosis, stenosis, parastomal hernia, bleeding and fistulation

• Double barrel 
• Loop 
• End 
• Hartmans

• 1 - Ileostomy or urostomy
• 2 - Sigmoid/descending colostomy
• 3 - Transverse colostomy

• Ideal Stoma Characteristics:
• • Red
• • Round
• • Raised (about 1" protrusion)
• • Lumen at center of stoma
• • Smooth skin surface

• Sites to Avoid:
• • Scars/Wrinkles
• • Skin Folds/Creases
• • Bony Prominence
• • Under Pendulous Breasts
• • Suture Lines
• • Umbilicus
• • Belt/Waistline
• • Hernia
• • Mobile Abdominal Tissue
• • Radiation Sites

• Other Considerations:
• • Type of Ostomy
• • Occupation
• • Impairments (e.g. visual, physical)
• • Sports/Activity Level
• • Prosthetic Equipment
• • Preference (surgeon, patient)
• • Posture
• • Contractures
• • Diagnosis
• • Age

• 1. Prolapse of mucosa (prolapse of distal loop mucosa is common) - commonest complication
• 2. Retraction
• 3. Necrosis
• 4. Stenosis
• 5. Herniation
• 6. Bleeding
• 7. Diarrhoea
• 8. Enteritis
• 9. Skin excoriation

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• Enumerate the premalignant conditions of colorectal cancer. Outline the preoperative mgmt. Of a patient undergoing anterior resection for carcinoma of the rectum. 55