Sabiston 2 Flashcards
The molecular events in CRC
include early APC (adenomatous polyposis coli) gene mutations, subsequent activating mutations in the oncogene KRAS, as well as mutations resulting in inactivation of the tumor suppressor gene TP53
CpG Island Methylator Phenotype
- involves a mutation of the BRAF gene resulting in inhibition of normal colon cell apoptosis.
- development of hyperplastic or sessile serrated adenomas or polyps > prone to epigenetic silencing of genes within “CpG islands”
- The hMLH1 gene (one of the DNA repair genes involved in Lynch syndrome) is one of the best characterized genes that undergoes this type of epigenetic silencing by CpG hypermethylation.
- result in a microsatellite instable-high (MSI-H) cancer if there is further gene mutation or methylation.
- most cancers arising from sessile serrated adenomas will have a MSI-H phenotype and are often located in the right colon.
Microsatellite Instability Mutator Pathway
- These genes include mutL homologue 1 (MLH1), MLH3, mutS homologue 2 (MSH2), MSH3, MSH6, or PMS1 homologue 2 (PMS2)
- These associated cancers will be MSI-H
- often characterized by location in the proximal colon, large local tumor, typical absence of metastatic disease, and poor tumor differentiation.
- When this occurs in patients with sporadic cancer, they are often elderly; when this occurs in the hereditary form (i.e., Lynch syndrome), patients are often younger (<50 years old)
- Testing for the presence of a BRAF mutation will aid in differentiating sporadic (BRAF mutation present) from inherited forms
Epithelial-Mesenchymal Transition
- Epithelial-mesenchymal transition is the process whereby cells lose their epithelial functional and morphologic functional features and gain a “mesenchymal” phenotype.
- Through this process, locally growing cancer cells gain the ability to invade through the bowel wall and spread to regional lymph nodes.
- Once cancer cells reach a metastatic site, they must reverse this process and undergo mesenchymal-to-epithelial transition.
Polyp
endoscopic appearance into pedunculated (with a stalk) sessile (flat)
histologic appearance
(adenomas, hamartomas, inflammatory, serrated, etc.).
Nonneoplastic Polyps
- Hyperplastic polyps :
> small sessile lesions, usually less than 5 mm, consisting of elongated colonic crypts with a papillary configuration of epithelial cells without atypia.
> They are common colonic polyps, frequently grossly indistinguishable from small adenomas. - Inflammatory polyps (pseudopolyps) are found in regions of healing inflammation.
> may be large, mimicking a neoplasm.
> found in diseased colons otherwise at risk for cancer (e.g., in IBD) - Hamartomas
> uncommon polyps found in the GI tract
> sporadic or related to a genetic syndrome such as Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome, and PTEN hamartoma syndrome. - No malignant potential.
- Removal is indicated for obstructive symptoms or bleeding.
Serrated Polyps
three types:
> hyperplastic polyps (which are not considered precancerous)
> sessile serrated polyps
> traditional serrated adenomas.
- Sessile serrated polyps and traditional serrated adenomas are combinations of adenomatous and hyperplastic polyps, sharing features of both types including colonic crypts with a saw-tooth serrated configuration and nuclear atypia :
increased risk of CRC
follows the serrated neoplasia pathway in contrast to the classic adenoma–carcinoma pathway seen in adenomatous polyps. These polyps should be removed, and patients should be followed with serial endoscopy.
Neoplastic Polyps
- All adenomas have a malignant potential.
> Tubular adenomas
Villous adenomas
Tubulovillous adenomas
The most common type are tubular adenomas,
frequently pedunculated.
- Villous adenomas are commonly sessile.
The risk of malignancy increases dependent on the size (large), gross shape (sessile), histologic type (villous), and grade of dysplasia.
Patients with an advanced adenoma defined as
- size at least 1 cm
- high-grade dysplasia
- tubulovillous or villous histology are at a significantly increased risk of developing CRC.
Polyp Excision
forceps and snares.
Pedunculated polyps >
removed using cold or hot snare polypectomy.
Sessile polyps > elevated from the underlying muscularis by injection of saline and then excised using an assortment of techniques.
Sessile polyps with a central depression that do not elevate adequately with saline injection (nonlifting sign) are at increased risk for perforation with endoscopic removal and at higher risk of harboring neoplasia and are commonly referred for surgical removal by segmental colectomy.
Large polyps that cannot be removed endoscopically are also referred for surgery.
Larger polyps can also be removed endoscopically using techniques such as endoscopic mucosal resection and endoscopic submucosal resection.
Malignant Polyps
Malignant polyps are those in which histologic examination following removal of a polyp reveals a focus of carcinoma that has invaded through the muscularis mucosa.
The question that arises is whether complete endoscopic removal of these polyps is sufficient.
Carcinomas that do not pass the muscularis mucosa are considered “carcinoma in situ” and do not carry metastatic risk. However, those that invade the muscularis mucosa harbor a significant risk of local recurrence and lymph node metastasis.
High Risk Polyp
- Malignant polyps are commonly referred for completion colectomy in cases of
- pedunculated Haggitt level 4
- sessile Kikuchi level Sm2 and Sm3
- histologic poor differentiation
- lymphovascular invasion
- incomplete removal or close resection margins
Recommendations for repeat colonoscopy following endoscopic removal of polyps
see
Familial Adenomatous Polyposis
- germline mutation in the APC tumor suppressor gene which is responsible for regulation of β-catenin and located on chromosome 5q21
fewer than 100 adenomas
are considered to have attenuated FAP (AFAP)
A variety of benign and malignant extracolonic manifestations have been described in FAP.
- gastroduodenal adenomas and carcinoma
- desmoids
- osteomas
- epidermoid cysts
- papillary thyroid carcinoma
- small bowel polyps and carcinoma
- congenital hyperplasia of the retinal pigment epithelium (CHRPE)
- dental anomalies
Inherited colorectal cancer syndromes
see
the second most common cause of death in FAP patients
Duodenal adenomas occur in 30% to 70% of patients with FAP, and there is a predilection for the ampullary and periampullary regions.
The lifetime risk for duodenal cancer is 4% to 10%, constituting the second most common cause of death in FAP patients
desmoid tumors
- About half of FAP-associated desmoid tumors arise intraabdominally in the bowel mesentery and 40% develop in the abdominal wall.
- Surgery of intraabdominal desmoid tumors, in general, is not recommended
- NSAIDs and antiestrogens showed similar outcomes to surgery. Combination chemotherapy, including doxorubicin, seems to be the best option for progressively growing intraabdominal desmoids.
CHRPE
CHRPE is a benign lesion
characterized as well-delineated grayish-black or brown oval spots seen in 60% to 85% of FAP patients on fundoscopic scan.
Normally, this does not require intervention but can be used to help make a diagnosis
Gardner syndrome and Turcot syndrome
Gardner syndrome
(FAP with epidermal inclusion cysts, osteomas, desmoid tumors)
Turcot syndrome
(FAP associated with malignant tumors of the central nervous system)
Indications for genetic counseling
family history of FAP
personal history of more than 10 adenomas
personal history of adenomas
and an extracolonic manifestation of FAP.
For individuals suspected of AFAP, gene testing is recommended if 20 or more cumulative colorectal adenomas are found
Screening
Colorectal screening
> begins at age 12 , initiated with flexible proctosigmoidoscopy. If polyps are seen >colonoscopy is warranted.
If no polyps are identified on the initial flexible proctosigmoidoscopy > repeated every 1 to 2 years until the age of 35 and every 3 to 5 years thereafter
Patients at risk for AFAP should receive endoscopic screening with colonoscopy at
ages 12, 15, 18, and 21 years, and then every 2 years
About one-third of patients with AFAP can be managed long-term endoscopically by polypectomy
For the upper GI tract, screening
screening begins at 20 to 25 years of age.
Screening intervals are based on the Spigelman staging system.
Annual thyroid screening
Annual thyroid screening by ultrasound should be recommended to FAP patients
Proctocolectomy and IPAA
> reduce the risk of rectal cancer
especially with rectal mucosectomy and hand-sewn anastomosis.
> associated with higher morbidity than IRA
results in more frequent bowel movements
risk of nerve injury that can lead to sexual or urologic dysfunction.
Pelvic dissection can cause infertility due to adhesions
Timing of surgery in patients with familial polyposis
see
Indications for IPAA.
- Patients with rectal cancer
- a large polyp burden (>20 synchronous adenomas, adenoma with high-grade dysplasia, large (>30 mm) adenomas)
- severe familial phenotype (>1000 synchronous adenomas)
stapled anastomosis Vs Handsewn
The benefits of a stapled anastomosis ( Keep anal Transition Zone )
> better function (less risk of incontinence)
> fewer complications
> easier to survey
> anal transitional zone adenomas may possibly be treated endoscopically or transanally.
The benefit of a handsewn IPAA ( Removes It )
> reduced incidence of anal transitional zone adenomas,
> worse bowel function.
This procedure can be performed with or without a diverting ileostomy
A temporary diverting ileostomy Benefits
- mitigate the effects of anastomotic leakage
- prevent pelvic sepsis , fistulization, and thus compromised pouch function.
- prevent the need for relaparotomy.
Subtotal colectomy and IRA
- Good functional outcomes
- long-term follow-up of the retained rectum.
- risk of metachronous rectal cancer 30%.
> recommended for patients with :
- few rectal polyps
- AFAP,
- family history of a mild phenotype
- young women with desire to become pregnant after recommendations of genetic counseling.
IRA should not be performed in :
- patients with a severely diseased rectum
(adenomas >3 cm diameter, adenomas with severe dysplasia, cancer, sphincter dysfunction, or a rectum containing more than 20 rectal adenomas) or in the presence of colon cancer
Proctocolectomy with end ileostomy
- very low rectal cancer, when sphincter preservation is not possible
- in cases of malignant transformation after IPAA
- or ileal pouch failure
- or in cases in which there is poor sphincter function.
Post Surgery
- chemoprevention after surgery because proctocolectomy with IPAA or a colectomy with IRA can retain “at-risk” rectal mucosa, and the duodenal mucosa remains “at risk” in all these patients.
- Chemoprevention (i.e., taking medications that slow polyp growth such as sulindac or celecoxib) should not replace routine endoscopic surveillance.
- Regular follow-up is mandatory after any procedure.
- Standard care includes perianal digital and flexible endoscopic examination at yearly intervals.
MUTYH-Associated Polyposis
- MUTYH gene, located on chromosome 1.
- CRC risk is increased twenty-eight fold for individuals with biallelic MUTYH mutations
indications for MUTYH gene testing:
- patients with 10 to 100 polyps
- siblings of patients with biallelic MUTYH gene mutation,
- patients with early-onset CRC (<44–55 years)
- or children of monoallelic or biallelic MUTYH gene mutation carriers
MAP Tx and Screen
- colonoscopy every 1 to 2 years
- Subtotal colectomy with IRA is recommended if endoscopic management fails or if CRC develops.
- Patients with rectal cancer in MAP should be considered for proctocolectomy and IPAA.
- Esophagogastroduodenoscopy with a side-viewing gastroscope to more accurately examine the ampulla should be performed to evaluate for duodenal adenomatous neoplasia.
- This screening should start at the age of 30 and be repeated every 3 to 5 years if the exam is normal
Peutz-Jeghers Syndrome
- 39% lifetime risk of CRC
- 90% lifetime risk of cancer, including colorectal (most common)
- 90% of PJS patients will develop hamartomatous polyps, most commonly in the small bowel, followed by the colon, stomach, and rectum
- mutation of the STK11/LKB1 gene located on chromosome 19p
Polyps differ histologically from juvenile polyps
Polyps differ histologically from juvenile polyps in that they arise due to an overgrowth of the muscularis mucosa rather than the lamina propria.
PJS is a clinical diagnosis based on any one of the following World Health Organization criteria:
(1) three or more histologically confirmed Peutz-Jeghers polyps
(2) any number of PJ polyps with a family history of PJS
(3) characteristic, prominent, mucocutaneous pigmentation with a family history of PJS
(4) any number of Peutz-Jeghers polyps and characteristic prominent, mucocutaneous pigmentation
Screening
- at 8 to 10 years of age with an evaluation of the small bowel.
- repeat evaluation at the age of 18 and then at 2- to 3-year intervals.
- Males > annual testicular physical examination starting at age 10 years
- females > annual pelvic examination and Papanicolaou stain starting at age 18 to 20 years
- Women > breast physical examinations every 6 months and yearly mammogram and breast MRI starting at age 25 years.
- Colonoscopy and upper endoscopy should start in the late teens and be repeated every 2 to 3 years for both genders.
- Pancreatic cancer screening involves endoscopic ultrasound or magnetic resonance cholangiopancreatography along with serum CA19-9 every 1 to 2 years starting at age 25 to 30 years.
Tx
- Polypectomy
- Asymptomatic gastric or colonic polyps larger than 1 cm should be removed endoscopically.
- Small bowel polyps larger than 1 to 1.5 cm or those that are have grown rapidly should be removed to decrease future complications such as bleeding and intussusception.
- Surgery is most commonly reserved for symptoms, the most common being obstruction (caused by intussusception) and bleeding in the small bowel.
What to add in Surgery
push enteroscopy or combined laparoscopy/laparotomy with endoscopy in the operating room as these small bowel polyps may not be visualized by other means
Juvenile Polyposis Syndrome
- hamartomatous intestinal polyps
- clinically diagnosed :
> five or more juvenile polyps in the colorectum
> multiple juvenile polyps throughout the GI tract
> any number or juvenile polyps with a family history
> or juvenile polyposis.
Genes ?
Two genes, SMAD4 (chromosome 18q) and BMPR1A (chromosome 10q)
Screening
- Screening by colonoscopy should begin between the ages of 12 to 15 years.
- If there are no polyps, colonoscopy should be repeated in 2 to 3 years.
- When polyps are present and removed, colonoscopy should be done annually
Surgical indications
- presence of high-grade dysplasia or cancer
- polyp burden cannot be effectively managed endoscopically.
Prophylactic colectomy may be considered for patients with poor surveillance compliance or in patients with family history of CRC.
Lynch Syndrome
- Genes (MLH1, MSH2, MSH6, PMS2, EpCAM)
- ## Mutations in MLH1 and MSH2 account for up to 90% of patients with Lynch syndrome
Amsterdam II citeria.
- Three or more relatives with hereditary nonpolyposis colorectal cancer–associated cancer (colorectal cancer or cancer of the endometrium, small bowel, ureter, or renal pelvis) plus all of the following:
- One affected patient is a first-degree relative of the other two.
- Two or more successive generations are affected.
- Cancer in one or more affected relatives is diagnosed before the age of 50 years.
- Familial adenomatous polyposis is excluded.
- Pathologic diagnosis of cancer is verified.
What Mutation Goes Against Lynch Syndrome
The presence of BRAF mutations in an MSI CRC is evidence against the presence of Lynch syndrome.
Lifetime Risk For CRC in Lynch
The estimated lifetime risk for CRC is 70% for men and 40% for women.
Lynch syndrome–associated CRCs show a predilection for the right colon as compared to sporadic CRC
Regarding Adenomas in Lynch
Compared with patients with AFAP or MAP, patients with Lynch syndrome develop few colorectal adenomas by the age of 50 years (usually fewer than three adenomas).
Histologic features in Lynch
Histologic features showing
- poor differentiation
- mucinous or signet-ring cell histology
- tumor-infiltrating lymphocytes
- lymphoid host response are common.
Most common extracolonic cancer in Lynch
Endometrial adenocarcinoma is the most common extracolonic cancer (lifetime risk of 32%–45%).
Ovarian, gastric, small bowel, urinary tract, brain, and pancreas cancers
in the following situations should be tested for MSI
- Colorectal cancer diagnosed in a patient before age 50.
- Presence of synchronous/metachronous colorectal or other hereditary nonpolyposis colorectal cancer (HNPCC)–related tumors
(including endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, brain (usually glioblastoma), sebaceous gland adenomas and keratoacanthomas, and carcinoma of the small bowel), regardless of age.
- Colorectal cancer with the MSI histology
(defined by the presence of tumor-infiltrating lymphocytes, Crohn-like lymphocytic reaction, mucinous/signet-ring differentiation, or medullary growth pattern) diagnosed in a patient before age 60. - Colorectal cancer diagnosed in at least one first-degree relative with an HNPCC-related tumor in which one cancer was diagnosed before age 50.
- Colorectal cancer diagnosed in at least two first- or second-degree relatives with HNPCC-related tumors, regardless of age.
When Screening for CRC
- Screening for CRC by colonoscopy is recommended in persons at risk
(first-degree relatives of known MMR gene mutation carriers who have not had genetic testing)
or those affected with Lynch syndrome every 1 to 2 years, - beginning at 20 to 25 years of age or 2 to 5 years before the youngest age of diagnosis of CRC in the family if diagnosed before age 25 years
For MMR germline mutation–positive patients Screening
- annual colonoscopy
- pelvic examination and endometrial sampling annually starting at age 30 to 35 years.
- screening of ovarian cancer should be offered beginning at the same age.
- Hysterectomy and bilateral salpingo-oophorectomy should be offered to women with Lynch syndrome undergoing colectomy, in all women over age 40 years or who have finished childbearing.
- Screening for gastric cancer EGD with gastric biopsy of the antrum at 30 to 35 years, and subsequent surveillance every 2 to 3 years can be considered based on individual patient risk factors.
- Screening for cancer of the urinary tract should be considered for persons at risk for or affected with Lynch syndrome, with urinalysis annually starting at age 30 to 35 years.
For Lynch , total or segmental Resection
- The cumulative risk of metachronous CRC in patients with segmental colectomy is
16% at 10 years
41% at 20 years
62% at 30 years.
there is superior cancer risk reduction with total colectomy for the treatment of colon cancer in the setting of Lynch syndrome, and total abdominal colectomy with IRA is the preferred treatment for most patients.
For patients with Lynch syndrome and rectal cancer, the rectal cancer should be treated based on standard oncologic principles, as in sporadic rectal cancer
Consideration for less extensive surgery should be given in patients older than 60 to 65 years and those with underlying sphincter dysfunction. Annual colonoscopy should be performed after segmental resection of colon cancer.
fused PET/CT scans are usually not used for initial staging for CRC, When its used ?
fused PET/CT scans are usually not used for initial staging but may be used in patients with
contrast allergy/renal failure or in equivocal cases
Prognostic Factors
- serum carcinoembryonic antigen (CEA) levels,
- the presence of tumor deposits within the lymph drainage area of a cancer
- (lymphovascular and perineural invasion respectfully)
The histologic grade of the tumor (low grade vs. high grade)
histologic subtypes such as mucinous and signet ring adenocarcinomas, which are usually more aggressive and carry a worse prognosis.
The circumferential resection margin should be reported by the pathologist, as well as the proximal and distal margin status and in rectal cancer, the completeness of the mesorectal excision.
molecular markers for somatic and germline mutations are investigated, such as
MSI, KRAS, BRAF, and NRAS mutations
which can help in both prognosis and treatment planning.
anatomic vascular landmarks
- The ileocolic pedicle originates from the superior mesenteric vessels just caudal to the second portion of the duodenum.
- The middle colic vessels originate from the superior mesenteric vessels at the level of the inferior margin of the pancreas.
- The inferior mesenteric vein can be easily identified at the level of the ligament of Treitz (Fig. 52.64).
- The IMA originates from the aorta, 2 to 3 cm caudal from the area where the IMV is identified; its origin is surrounded by the mesenteric and hypogastric nervous plexus.
- The left colic artery originates about 2 cm distally to the origin of the IMA.
The vascular supply of the colon, which is mobilized and utilized for the anastomosis, relies on
marginal vessels located in the mesocolon
Right-Sided Tumors Steps ( cecum and ascending colon )
- detachment of the right abdominal side-wall attachment
- the vascular pedicles are ligated once the right colon has been fully mobilized
- division of the ileocecal pedicle at its origin from the superior mesenteric vessels and division of the right colic vessels , and right branch of the middle colic vessels is divided
- lymphatic tissue that surrounds the superior mesenteric vein can be removed en bloc
- terminal ileum is divided with a stapler 5 to 6 cm from the ileocecal valve and the transverse colon at the junction between its mid and proximal third.
- omentum has to be removed en bloc, together with the gastrocolic ligament that is divided along the gastroepiploic arcade
- extracted through a Pfannenstiel incision that has fewer short- and long-term complications
- ileotransverse anastomosis
In laparoscopy or robotics, the colectomy is usually performed with a medial to lateral approach with initial vascular control and then detachment from the abdominal side wall.
An intracorporeal anastomosis vs Extracorporeal
An intracorporeal anastomosis seems to bring advantages in terms of
- fewer anastomotic complications (leaks and twists)
- faster recovery of bowel function and discharge
Tumors of the Transverse Colon
- Right extended colectomy
- middle colic vessels are divided at their origin at the level of the inferior margin of the pancreatic neck
- ileocolic anastomosis is made at the distal third of the transverse colon
Tumors of the Splenic Flexure
- extended right-sided resection, to encompass the splenic flexure, Or resection of the splenic flexure alone
- The inferior mesenteric vein is ligated at the level of the ligament of Treitz and the left colic artery is divided at its origin from the IMA and the specimen is taken en bloc with the omentum
- anastomosis between the transverse and the descending colon.
In selected cases, where the mesentery of the colon is thick and the colon is short, this colocolic anastomosis can compress and obstruct the duodenum at the ligament of Treitz. In these cases, extended right hemicolectomy with ileo-descending anastomosis is preferable.
Left-Sided Tumors
- Left hemicolectomy
- high ligation of the IMA at its origin
- IMA can also be ligated 2 to 3 cm more distally without compromising the oncologic outcome but lowering the risk of injuring the mesenteric and hypogastric nervous plexus
- inferior mesenteric vein is divided
- splenic flexure must be fully mobilized, coloepiploic detachment, detachment of the mesocolon of the splenic flexure and distal transverse from the pancreas, and left abdominal gutter detachment.
- anastomosis without tension between the left colon and the proximal rectum below the rectosigmoid junction
- Restoration of bowel continuity is made with a transanal circular stapler that should have a caliber of about 3 cm
A damage of the hypogastric nervous plexus carries the risk of
genitourinary complications, including retrograde ejaculation in males, bladder dysfunction, and vaginal dryness in women.
Management of sigmoid and left colon obstructions
A segmental resection of the primary tumor is typically performed.
If the proximal large bowel has perforated or is showing signs of ischemia, a subtotal colectomy is completed
Current evidence supports the option of a primary anastomosis in appropriate patients who are hemodynamically stable
A proximal diverting stoma may also be exteriorized combined with a primary anastomosis. This does not reduce the anastomotic leak rate but may decrease the quantity of leaks requiring reoperation
Stent in Left Obstruction
Stenting has been shown to permit
higher rates of primary anastomosis
decreased wound infections
and a higher rate of completion of surgery laparoscopically.
Stenting is contraindicated in suspected ischemic or perforated bowel.
Treatment of right-sided obstructions
oncologic segmental resection.
In most cases, a primary ileocolic anastomosis can be performed safely, but for patients with a high risk of anastomotic failure, a diverting stoma can be exteriorized.
indications for neoadjuvant chemoradiation in Rectal Ca
clinically T3
node positive rectal cancers
cancers in close proximity of the sphincter in whom sphincter sparing is desired
Endoscopic submucosal dissection
- used for lesions that are superficial
- hollow cap is placed over the tip of the endoscope.
- After submucosal injection has been performed to lift the lesion away from the underlying muscularis
- suction is applied to the colonoscope when the cap is positioned over the lesion
- The lesion is drawn into the cap by suction
- the snare that fits around the cap then is tightened, cutting off the area of mucosa that has been aspirated into the cap
endoscopic submucosal resection
- for deeper through the muscle wall
- submucosal injection is performed to facilitate dissection of a lesion off the underlying colon wall after the margin has been scored
Traditional criteria for performing a local excision for a rectal cancer
- small lesions (<2 cm in diameter)
- well-differentiated cancers within reach of the index finger
- lesions that are mobile (not fixed).
- T1 lesions are ideal
- cautery is used to score a 1-cm margin around the lesion
- full-thickness incision is performed down to perirectal fat
Local excision is safe when performed for lesions that are located
lateral to or posterior to the rectum due to the presence of the mesorectum.
If these lesions are located in the anterior rectum in women, there is risk of iatrogenic rectovaginal fistula or, in the case of men, injury to the prostate
as one goes higher above 6 or 7 cm, there is concern that one may be intraperitoneal.
Low Anterior Resection
- After vascular division similar to left colectomies,
- peritoneal reflection of the rectum is divided at the level of the sacral promontory
- the rectum with its proximal mesorectum is gently pulled anteriorly entering the avascular “cotton candy” plane between the fascia of the mesorectum and the presacral fascia
- avoid any injury to the hypogastric nerves
- Anteriorly, the cul-de-sac is divided, and the rectum is dissected from the anteriorly located seminal vesicles in males and the vagina in females.
- The dissection is continued distally and the rectum and the mesorectum are divided 5 cm below the cancer
- For cancers located in the distal two thirds of the rectum, the dissection must be continued more distally, dissecting the rectum away from the prostate along the fascia of Denonvilliers.
- Posteriorly, the rectum has to be dissected distally, up to the level of the levator muscles en bloc with the entire mesorectum, keeping the mesorectal fascia intact
-colorectal anastomosis made with a circular stapler inserted transanally. - Air is then insufflated into the rectum through the anastomosis while the proximal colon is occluded, and the pelvis is filled with water in order to exclude the presence of leaks
- loop diverting ileostomy is performed to protect the distal colorectal anastomosis, especially in patients who have received preoperative chemoradiation.
what defines the quality of a TME
The integrity of the visceral fascia is a crucial point that defines the quality of a TME and is directly related to the DFS interval.
The proper excision along the anatomic plane is essential in order to obtain free circumferential radial margins, thus reducing the local recurrence rate below 5%; it also results in a significant decrease in the frequency of urinary and sexual dysfunction (retrograde ejaculation and impotence).
How long to keep The diverting stoma
The diverting stoma is usually maintained for at least 8 weeks after surgery and is closed only after the perfect healing of the anastomosis has been confirmed with a gastrografin enema or with endoscopy
Tumors located in ultradistal portion of the rectum (i.e., at the level of the dentate line or just above it)
- In young and fit patients with good preoperative sphincter function
- sphincters are not infiltrated with cancer and do not need to be sacrificed for oncologic reasons
- anastomosis between the colon and the anal canal is feasible.
- The ultradistal rectum dissection and reconstruction has to be performed transanally
- With a standard mucosectomy, the distal mucosa is peeled off from the internal sphincter. Ideally, 1 to 2 cm of mucosa above the dentate line should be saved
If the cancer is lower ans small > asymmetrical mucosectomy en bloc with the underlying internal sphincter on one side of the anal canal, sparing part of the distal mucosa and sphincter
If the cancer involves a larger part of the anal canal, an intersphincteric dissection must be done > the internal sphincter—responsible for resting pressure of the anal sphincter—is removed circumferentially: functional results are poor due to the loss of part of the sensation and the decrease of resting anal pressure.
Abdominoperineal Resection
- complete excision of both the rectum and the anus, along with the sphincter apparatus, must be performed along with creation of a permanent colostomy
- The IMA is divided, the descending colon is mobilized and divided above the rectosigmoid junction
- the rectum is dissected according to the TME principles to the level of the levator ani.
- colostomy aperture is created
- purse-string suture is placed around the anus
- an elliptical incision is made around the anus that is then excised en bloc with the sphincter.
- Dissection continues cephalad until the abdominal plane of dissection is reached.
- The specimen is removed through the pelvic incision and the perineum is closed in layers
- pelvis can often be filled with an omental pedicle
- perineal defect can be closed using a rectus abdominis flap or gracilis muscle flap.
APR Cont
wider excision has been proposed that allows a more cylindrical resection avoiding the risk of “coning” toward the rectum.
After the abdominal part of the operation is completed, the patient is rotated in a prone jackknife position.
A wider elliptical incision is made up to tip of the coccyx (that can be removed with the specimen) and the sphincter apparatus is removed en bloc with the levator ani in a cylindrical manner.
The wide perineal defect, if needed, can be closed with a biologic mesh or with a muscle flap.
APR Vs LAR in Recurrence
APR carries intrinsic risk of higher recurrence rates (up to 33%) compared to low anterior resection.
This is in part explained by the fact that APR is done in more aggressive cancers, but another explanation is the fact that there is an intrinsic higher risk of specimen perforation and a higher rate of positive circumferential margins (up to 40%) in patients undergoing APR
the residual colon may be too short to reach the pelvis for a tension-free anastomosis
- complete mobilization of the splenic flexure
- colon can be transposed through a “retroileal” transmesenteric route.
- This gives the surgeon 4 to 5 cm of additional length
If the colon is still under tension
- rotate the right colon.
- the middle colic and the right colic vessels are divided.
- The colon is transected at the site of ischemic demarcation (generally the hepatic flexure) and the residual right colon, whose blood supply now relies on the ileocolic pedicle, is rotated counterclockwise and mobilized to reach the rectal stump in the pelvis
The incidence of anastomotic in ileocolic and coloanal
from 1% to 3% in ileocolic anastomoses to up to 20% in coloanal anastomoses
Risk factors associated with postoperative dehiscence (Leak)
male gender
obesity
low extraperitoneal anastomoses
ASA score III to V
emergency operations
intraoperative complications
use of oral anticoagulants
nutrition status
hospital size and volume.
The majority of leaks become apparent between
the second and seventh postoperative days
with median time of 5.5 days,
but up to 12% can appear 1 month after surgery, making the diagnosis more challenging.
Tx If the leak is subclinical with minimal discharge from the drains and no systemic signs
managed conservatively with close clinical observation, broad spectrum antibiotics, bowel rest, and parenteral nutrition
If a small perianastomotic abscess is demonstrated with no abdominal collections or free air and without systemic symptoms, an attempt of percutaneous drainage should be made with close clinical observation
In patients with signs of peritonitis or signs of sepsis, even if minimal
reoperation is required and should not be delayed.
Abdominal exploration allows peritoneal lavage and reposition of new drains if needed.
If possible, a laparoscopic approach may be preferred in order to minimize septic contamination of the abdominal wall
what extra can be done in left-sided colectomies with leak
intraoperative endoscopic exploration of the anastomosis is helpful to determine the extent of the leak, and it also allows colonic lavage.
If the leak involves less than one third of the anastomosis and the abdominal contamination is minimal
a diverting stoma may be sufficient.
If the leak is larger or the anastomosis is disrupted, it has to be dismantled with the creation of a terminal stoma.
An ileocolic anastomosis in right-sided resections can be managed ideally by redo of the anastomosis, but if the patient is unstable, the anastomosis has to be dismantled and an end ileostomy constructed.
Necrosis of the Transposed Colon
- mimic an anastomotic leak
- must be immediately differentiated from a simple dehiscence because the treatment must be more aggressive.
The diagnosis is often made with abdominal exploration or intraoperative endoscopy > shows a clear demarcation line.
Its treatment requires immediate dismantling of the anastomosis with creation of a terminal stoma.
Bleeding
Major bleeding, with hemodynamic instability
> caused by small arterioles at the staple lining.
Treatment is usually endoscopic with positioning of clips at the suture line, epinephrine injection, or electrocoagulation.
If endoscopy fails, angiographic treatment is possible, but it might lead to ischemia of the anastomotic rim and subsequent possible further leaks
Twisting
- almost exclusively in extracorporeal ileocolic anastomosis after laparoscopic hybrid right colectomies
- immediate swelling and edema of the small bowel
- can lead to ischemia and gangrene of the intestine. Immediate redo of the anastomosis is necessary
Strictures
Risk factors are the use of a small-diameter stapler (25-mm circular staplers should never be used in colorectal anastomosis in adults)
anastomotic leaks
ischemia
radiation.
Treatment is usually endoscopic with balloon dilation or placement of radial incisions or positioning of endoluminal stents.
Redo of the anastomosis may be necessary in strictures not responding to the endoscopic treatment
Low Anterior Resection Syndrome
- present in up to 80% of patients undergoing a low anterior resection
- frequency, multiple fragmented bowel movements, a sensation of incomplete emptying, incontinence, constipation, and diarrhea.
- symptoms improve 1 year or more after the resection, but long-term dysfunction is described in the majority of patients
Low Anterior Resection Syndrome 2
- may be due to an injury of the internal sphincter
- loss of sensitivity in the anorectal mucosa
- loss or impairment of the rectoanal-inhibitory reflex
- reduction of the capacity of the rectal reservoir
- and/or loss of compliance of the transposed colon.
incidence is higher in patients undergoing TME
in those with coloanal anastomosis
in those who received neoadjuvant chemoradiation
and in those who had an anastomotic leak.
LAR Syndrome 3
Preventive technical mechanisms
- anastomosis with a 5 to 6-cm colonic J-pouch
- or with a transverse coloplasty
- or side-to-end colorectal anastomosis
Tx of LAR Syndrome
empirical, based on diet control, balanced use of loperamide associated with fiber products, physical therapy including biofeedback, and transanal irrigation.
In a minority of highly symptomatic patients with low quality of life, after failure of conservative treatment, the construction of a stoma can be necessary as a definitive treatment.
Five-year survival rate
stage I cancer 90%
stage II, 75%
stage III (with positive lymph nodes) 50%.
Patients with distant nonresectable metastases 5%.
Patients with resectable liver metastases 60%.
How to Do Coloplasty
A longitudinal 10-cm colotomy is made about 5 cm from the distal end of the transposed colon and is then sutured transversely in order to widen the colon and increase it compliance
Follow up after Sx
CEA levelsevery 6 months for 5 years after surgery
then annually.
Rising levels of CEA > additional tests
Colonoscopy 1 year after surgery (or 3–6 months after surgery if the entire colon was not completely investigated at the time of diagnosis);
> further colonoscopies should be repeated every 3 years if no adenomas were detected and every year if adenomatous polyps are found until the colon is found clean.
Chest and abdominal CT scans are performed annually.
Stage II tumors: tumor penetrates into pericolic fat, negative lymph nodes , Adj Chemo ?
relative indications for chemotherapy:
- poorly differentiated cancer (G3–4)
- vascular and perineural invasion
- obstruction
- perforation
- adjacent organ invasion (pT4)
- inadequate number of examined number lymph nodes (<12)
MSI-H condition (deficient expression of MMR genes)
more frequent in stage II disease (22%) than in stages III (12%) and IV (3%)
appear to have a favorable prognostic significance in stage II
Stage III disease: positive lymph nodes
Adjuvant chemotherapy is indicated in stage III patients.
5-FU and FA are combined with oxaliplatin in the FOLFOX protocol.
In the CAPOX (or Xelox) regimen, oral capecitabine is used instead of 5-fluorouracil folinic acid (5-FUFA).
In low-risk patients, 3 months (four cycles) of CAPOX was not inferior to 6 months of the same regimen
In high-risk patients, 3 months of the CAPOX regimen was sufficient
With regard to the FOLFOX regimen, 6 months seems superior to 3 months, regardless of the risk group
Metastatic disease
- Anti-EGFR antibodies (panitumumab, cetuximab)
> pan-Ras wild-type and BRAF wild-type neoplasia. - BRAF-mutated metastatic disease
> FOLFOXIRI (oxaliplatin + irinotecan + 5-FUFA) and bevacizumab
If the primary tumor is right sided
- Doublets (FOLFOX or FOLFIRI) or the triplet FOLFOXIRI in fit patients, in combination with anti–vascular endothelial growth factor antibody (bevacizumab), could be the best choice.
In left-sided primary tumors
the addition of cetuximab or panitumumab to FOLFOX/FOLFIRI could be the first line of treatment.
However, also in this case, the use of FOLFOXIRI can be considered.
In older or unfit patients, unable to tolerate doublets, capecitabine with bevacizumab is an appropriate treatment.
If the goal of treatment is the resection of hepatic disease, how many cycle and when to stop
- no more than six cycles of chemotherapy should be administered before surgery
> in order to avoid hepatic toxicity (steatohepatitis with irinotecan and sinusoidal damage with oxaliplatin) - bevacizumab needs to be stopped 6 weeks before hepatic resection because of its detrimental effects on wound healing.
- Bevacizumab can be started 4 weeks after surgery or once the wounds have healed.
The pelvic floor disorders
- rectal prolapse or procidentia
- rectocele > bulging of the rectum into the posterior wall of the vagina
- cul-de-sac hernia > protrusion of the peritoneum between the rectum and the vagina, “enterocele” and “sigmoidocele”
- anismus > failure of the puborectalis and the external anal sphincter to relax during defecation
Anorectal Physiology Laboratory Tests
- Anorectal manometry
> evaluates the high-pressure zone (i.e., the length of the anal canal), the resting pressure, mostly due to the internal sphincter, the maximum voluntary pressure, and the squeeze pressure, due to the external anal sphincter
Normal resting pressure values are 40 to 80 mm Hg
The balloon expulsion test
Pudendal nerve terminal motor latency > Prolonged values are seen in traumatic injuries (spinal cord) or with stretch injury from obstetric trauma due to prolonged labor, chronic stretch injury as seen in long-standing defecation disorders, sacral nerve root damage or chronic diseases as diabetes.
normal = 2.0 ± 0.2 milliseconds
Electromyography , identify what
Patients with inappropriate or paradoxical puborectalis contraction fail to show a relaxation of the muscles when asked to push.
Imaging to Evaluate the Pelvic Floor
Endoanal ultrasound
> evaluate the integrity, thickness, and possible abnormalities (scars, fistulas) of the internal and external anal sphincter.
Defecography
> anatomic abnormalities, such as rectocele, rectal prolapse, internal rectal intussusception, and cul-de-sac hernia, as well as about functional disorders, such as nonrelaxation or paradoxical puborectalis contraction, perineal descent, and the degree of rectal emptying.
Colonic transit time
> studies colonic inertia
> In the healthy population, 80% of the markers should be expelled by day 5.
The cause of rectal prolapse
diastasis of the levator ani muscle
an abnormally deep cul-de-sac
a redundant sigmoid colon
a patulous anus
lack of fascial attachments of the rectum against the sacrum
Risk factors of rectal procidentia include
- age over 40 years
- female gender
- prior pelvic surgery
- chronic straining and constipation
- chronic diarrhea
- vaginal delivery
- multiparity
- pelvic floor dysfunction
- anatomic defects
- neurologic diseases/injuries
- psychiatric diseases that require constipating medications
Why incontinence in Rectal prolapse
complain of fecal incontinence (passive or urge incontinence) that is caused by the presence of a direct conduit, by the chronic stretching of the sphincter due to the prolapse, and by persistent stimulation of the rectoanal inhibitory reflex caused by the prolapsed rectum
one half of patients with incontinence have also pudendal neuropathy with a prolonged pudendal nerve terminal motor latency.
the cause of constipation in rectal prolapse
constipation or obstructed defecation (feeling of an incomplete rectal evacuation during defecation) that results from the “telescoping” of the bowel on itself creating a functional blockage that worsens with straining
Seen in Intra-rectal Prolapse
rectal Prolapse Vs hemorrhoids
the full-thickness rectal prolapse has concentric folds, whereas prolapsed hemorrhoids or rectal mucosa is characterized by radial folds,
What should You exclude for patient with rectal prolapse
- Colonoscopy to exclude CRC or other colonic pathology.
- A colonic transit study to differentiate constipation due to obstructed defecation from constipation due to slow colonic transit
- Endoanal ultrasound usually shows a thickening of the internal anal sphincter.
Type of Mesh Repair in Rectal Prolapse
- posterior mesh rectopexy
> mesh is fixed to the presacral fascia, below the sacral promontory, and to the rectum laterally - ventral mesh rectopexy
> limited anterior rectal mobilization and a mesh suspension to the sacral promontory.
The mesh is fixed to the anterior wall of the rectum and suspended to the sacral promontory
Advantages of this technique are the improvement in postoperative incontinence and constipation
what to use biologic or nonabsorbable mesh ?
recent literature shows no statistical improvement in recurrence and complication rates between biologic and nonabsorbable mesh
in which patient to resect Sigmoid
In these cases, a simultaneous resection of the redundant sigmoid can be performed in selected patients with coexisting constipation
For patients with a short (<5 cm) rectal prolapse
the Delorme procedure can be appropriate
For symptomatic intrarectal prolapse
the stapled transanal rectal resection (STARR) has been proposed as an alternative possible technique. It consists of a full-thickness rectal resection including the internal prolapse with a circular stapler (STARR) or a specific curved-shape stapler (Transtar).
why starr not done anymore
the onset of chronic proctalgia and stool urgency with postoperative incontinence have often been reported. Other complications of transrectal stapled repair are staple-line bleeding and, rarely, staple-line disruption and rectovaginal fistula (overall morbidity rate from 7%–21%).
Solitary Rectal Ulcer
The cause is multifactorial and includes internal rectal prolapse and abnormal/paradoxical contraction of the puborectalis muscle
Histologic examination of biopsies >
fibromuscular obliteration of the lamina propria, hypertrophied muscularis mucosae with muscular fibers between the crypts, and glandular crypt abnormalities.
SRUS Tx
mild to moderate symptoms :
medical treatment is usually effective
patient education and behavioral modification: high-fiber diet, stool softeners and bulking laxatives, avoidance of straining and/or anal digitations, minimizing time on the toilet, and the use of sucralfate, corticosteroid, and/or mesalamine enemas.
Surgical options include local excision of the ulcer, treatment of the rectal prolapse, or a defunctioning stoma for patients who have failed other options
Rectocele
The cause of rectocele explained by a muscular and/or neurologic damage to the rectovaginal septum (usually due to obstetric trauma) and due to the effect of chronic straining on the endopelvic fascia and on the posterior wall of the vagina
the cardinal symptom is difficulty in rectal emptying and the need to press against the posterior wall of the vagina or against the perineum in order to complete the rectal emptying (obstructed defecation).
Other symptoms include the sensation of a vaginal bulge,
Asymptomatic rectoceles
do not need treatment, while patients with a symptomatic rectocele are initially managed with a bowel regimen and fiber products in order to improve defecation.
Only selected patients with markedly symptomatic rectoceles unresponsive to medical treatment are candidates for surgery.
The goal of surgery is to remove the redundant tissue of the rectocele and to strengthen the rectovaginal septum.
