QI and DCR Flashcards
Micro-satellite instability is not restricted to Lynch Syndrome. What proportion of MSI/dMMR tumours are attributable to Lynch Syndrome?
In fact, only 15–20% of MSI/MMR-deficient (dMMR) tumors can be attributed to LS, and most MSI/dMMR tumors are sporadic. This emphasizes the importance of distinguishing these two entities for appropriate management.
What is the lifetime risk of colorectal cancer and endometrial cancer in patients with Lynch Syndrome?
The lifetime risk of CRC depends on sex and on the MMR gene, which is mutated.
In two recent international prospective studies including more than 3000 families, the lifetime risks of CRC at 70 years old for MLH1 and MSH2 gene mutation carriers ranged from 40% to 52%, with a slight male predominance.
The cumulative lifetime risks for colorectal malignancy were lower in patients with MSH6 and PMS2 gene mutations (approximately 15% and between 3% - 13%, respectively).
Endometrial cancer is the most common extracolonic cancer in LS, with lifetime risk estimates of 35–40% for MLH1, 46–53% for MSH2, up to 46% for MSH6, and 13% for PMS2.
What is the utility in testing for KRAS mutations?
How common is KRAS mutation?
The KRAS oncogene is mutated in approximately 35%-45% of colorectal cancers.
The most frequent mutations in this gene, point substitutions in codons 12 and 13, were validated as negative predictors of response to anti-epidermal growth factor receptor antibodies (Cetuximab and Panitumumab should only be used in KRAS-WT metastatic cases)
What is the size of an open endoscopic biopsy forceps?
6mm
(Radial Jaw 4 Biopsy Forceps, Boston Scientific, United States)
Describe the evidence for the use of Chromoendoscopy in the context of surveillance endoscopy in IBD patients.
In surveillance of inflammatory bowel diseases, chromoendoscopy identifies more patients with dysplasia only when compared with standard-definition white-light endoscopy.
It is associated with longer procedural time (+9 minutes) with no direct evidence of effect on preventing all-cause/cancer-specific mortality or time to interval cancer.
Ref:
Chromoendoscopy for Surveillance in Ulcerative Colitis and Crohn’s Disease: A Systematic Review of Randomized Trials. Clin Gastroenterology and Hepatology. November 2017.
Describe appropriate antibiotics prophylaxis in colorectal surgery.
When should they be given?
When should repeat doses be given?
Appropriate prophylactic regimens include single agent cover with intravenous cefoxitin (2nd Gen; broad activity against G+, G-, and some anaerobes), or dual agent cover with cefazolin and metronidazole. The use of second or third generation cephalosporins is not any more effective than a first generation drug when used in conjunction with metronidazole (see ref).
In the setting of β-lactam allergy, cefazolin may be substituted with clindamycin, gentamicin or ciprofloxacin.
It is recommended that antibiotics are administered within 60 minutes of surgery in order to achieve peak tissue levels. There is some evidence that administration greater than 120 minutes prior to surgery reduces efficacy.
Repeat dosing during longer operations is recommended for cefoxitin (2 hourly) and cefazolin (4 hourly). The pharmacokinetic profile of metronidazole is such that adequate tissue concentration is maintained for 6-9 hours.
- Skipper D, Karran S. A randomized prospective study to compare cefotetan with cefuroxime plus metronidazole as prophylaxis in elective colorectal surgery. Journal*
- of Hospital Infection. 1992;21(1):73-77.*
Summarise serrated colonic lesions.
Until 2010, colorectal serrated lesions were generally considered as harmless lesions and reported as hyperplastic polyps (HPs) by pathologists and gastroenterologists.
However, recent evidence showed that they may bear the potential to develop into colorectal carcinoma (CRC).
Therefore, the World Health Organization (WHO) classification has identified four categories of
serrated lesions:
1. Hyperplastic polyps (HPs)
2. Sessile serrated lesions (SSLs)
3. Traditional serrated adenoma (TSAs)
4. Unclassified serrated adenomas.
SSLs with dysplasia and TSAs are the most common precursors of CRC.
How do CRCs arise from serrated lesions?
CRCs arising from serrated lesions originate via two different molecular pathways, namely sporadic microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP), the latter being considered as the major mechanism that drives the serrated pathway towards CRC.
Unlike CRCs arising through the adenoma–carcinoma pathway, APC-inactivating mutations are rarely shown in the serrated neoplasia pathway.
Describe the distribution of colorectal cancer in Australasia according to BCCA data in terms of:
- Gender
- ASA
- Stage at diagnosis
- Elective versus emergency
- Location of tumour
- Rectal cancer patients receiving NAC
According to the 2021 BCCA data-set:
- 54% of patients were male
- 46% of the cohort were ASA III or higher
- Stage distribution is constant, with 10% presenting with metastatic disease, 60% presenting with stage II/III disease, and 30% presenting with stage I disease
- 80% of cases present electively
- Caecum/Ascending colon 30%, Rectum 30%
- Hepatic flexure, TC, Splenic flexure, rectosigmoid ~10%
- More than half of rectal Ca patients get NAC
What is Waldeyer’s fascia?
Describe the importance of this anatomical structure.
Waldeyer’s fascia, also known as the rectosacral fascia, is a thickened band which originates from the endopelvic/presacral fascia at the S2 to S4 level and passes caudally to fuse with the mesorectal fascia 3-5cm from the anal verge. This divides the retrorectal space into superior and inferior parts. It lies above the levator ani muscle at the level of the anorectal junction.
If Waldeyer’s fascia is encountered during surgery, the wrong surgical plane may be entered; failure to recognize Waldeyer’s fascia and to maintain dissection distally along the fascia may result in entrance into the rectum. Sectioning the fascia can provide access to the inferior portion of the RRS, resulting in successful mobilization of the rectum.
What are the boundaries of the retrorectal space?
The retrorectal space is a potential space within the extra-peritoneal compartment of the pelvis. It is bounded:
- Anteriorly by the rectum and posterior mesorectum’s visceral fascia
- Posteriorly by the sacrum covered by presacral fascia.
- Superiorly by the pelvic peritoneal reflection at the rectosigmoid junction
- Inferiorly lies Waldeyer’s fascia and the supralevator space
- Laterally, the presacral area is bounded by the ureterohypogastric fascia and extends to the ureters, internal iliac vessels, lateral sacral artery, the sympathetic trunk, hypogastric nerves, and the inferior hypogastric plexus at the lower levels.
What explains the heterogeneity of “Pre-Sacral Tumours”?
The retrorectal or pre-sacral space occurs at the confluence of the hindgut, bony pelvis, and neuroectoderm of the spinal cord. Hence, lesions arising in this space may arise de-nove from any of these structures or their congenital variants.
What are the surgically relevant contents of the pre-sacral space?
Discuss the anatomy of these neurovascular structures.
Surgically significant vascular structures include the
- Sacral venous plexus, formed primarily by the anastomosis of the middle and lateral sacral veins on the anterior surface of the sacrum.
- The middle sacral artery arising from the abdominal aorta before its bifurcation courses caudally within the midline just anterior to the lumbosacral spine. This vessel is more likely to be to the right than to the left.
- The lateral sacral arteries arise from the posterior trunk of the internal iliac artery and descend along the anterior aspect of the sacrum, dividing into smaller branches that enter the sacral foramina.
- The lumbosacral trunk runs across the ala of the sacrum to join the first sacral nerve and, together with the second and third sacral nerves, forms the sciatic nerve. The upper three sacral nerves lie in the sacral hollow where they are separated from bone by the piriformis and covered by parietal pelvic fascia. These nerves form the sciatic nerve after exiting the pelvis through the greater sciatic foramen below the piriformis.
- The superior and inferior hypogastric plexi and their adjoining hypogastric nerves closely approximate in the presacral space. The superior hypogastric plexus originates at the aortic bifurcation and ends in the superior portion of the presacral space bordered laterally by the iliac vasculature and inferiorly by the levator ani.
What is the intended fixation area on the sacral promontory when fixing the mesh of a LVMR?
What structures are at risk? Specifically which vessels?
A recent study in DCR (May 2022) showed that only 43% of tacks were placed in the intended fixation area; the anterior longitudinal ligament on the surface of S1, during cadaveric LVMR.
Other structures nearby include the superior hypogastric plexus (universally damaged), hypogastric nerves, the L5 disc, the iliac vessels (RCIA and LCIV), the ureters (~3cm) the first sacral nerve (4cm).
What is a “Chronic Perineal Sinus”?
What is the incidence of this following proctectomy?
How can it be prevented?
How can it be treated?
First reported by Miles in 1908, chronic perineal sinus (CPS), also referred to as “presacral sinus,” is defined as a perineal wound that does not heal after more than 6 months.
Poorly reported, the incidence is probably between 10-40%, with rates much higher in Crohn’s compared with UC, and especially high after pouch excision.
Preventative measures include:
- Pre-operative optimisation (smoking, diabetes, etc)
- Inter-sphincteric proctectomy
- TME
Treatment options include:
- Curettage and NPWT
- Gracilis flap
- VRAM flap
What is the difference between Lynch Syndrome and HNPCC?
HNPCC is defined clinically, usually as families satisfying Amsterdam I or II criteria.
Lynch syndrome is defined genetically, by the presence of a germline mutation in DNA mismatch repair (MMR) or EPCAM genes.
Not all HNPCC families have Lynch syndrome and not all Lynch syndrome families have HNPCC.
Define post-operative acute kidney injury.
What proportion of patients undergoing colorectal cancer surgery experience this?
What is the impact of PO-AKI on mortality?
PO-AKI occurs within 7 days of surgery and is a multifactorial process influenced by preoperative, intraoperative, and postoperative factors.
Northern European population-based data suggest that 20.3% of patients undergoing colorectal cancer resection experience PO-AKI.
PO-AKI and mortality have a dose-depedant relationship, with even mild PO-AKI resulting in a 2-3 fold increase in mortality at 3 months.
How is PO-AKI diagnosed?
Must have one of the following:
- ↑sCr ≥ 0.3 mg/dL (~30umol/L) within 48 h
- ↑sCr ≥ 1.5 baseline
- Urine output <0.5 mL/kg/h for 6 h
Describe the KDIGO classification of AKI
Which common peri-operative medications require dose-adjustment with PO-AKI?
Analgesia:
NSAIDS, morphine, codeine, tapentadol, tramadol, gabapentinoids should be strongly (re)considered in patients with stage II-III PO-AKI.
Anticoagulants:
Enoxaparin and NOACs require renally-adjusted dosing
Antibiotics:
Cephalosporins
Outline the impact of ileostomy-associated AKI on long-term renal function.
In the 3 months after ileostomy formation, 15% of patients experience a de novo or community-onset AKI
Of those, 28.5% develop stage III CKD within 12 months.
After ileostomy takedown, the risk of incident CKD is attenuated, but it remains significantly elevated among those who had an ileostomy-associated AKI.
Describe the mechanism of the “triple-whammy” of NSAIDS, diuretics, and ACEi/ARBs in the context of AKI.
- ACE inhibitors or ARBs decrease glomerular filtration by causing vasodilation of the efferent renal arteriole.
- Diuretics can also contribute to AKI by causing hypovolaemia.
- NSAIDs associated blockade of the COX-2 enzyme prevents prostacyclin synthesis, which causes afferent arteriolar vasoconstriction
Describe the method by which response to chemoradiotherapy in rectal cancer is assessed on MRI.
