Small bowel Flashcards
1
Q
What is your framework for considering small bowel tumours
A
Non-neoplastic
- haemangiomas
- hamartomas
- hyperplastic polyps
- heterotopic tissue (in Meckel’s)
- endometriosis & dermoid cysts
Neoplastic
- Benign (adnomas, leiomyomas, lipomas most common)
- adenomas (15% of benign SB tumours
- leiomyomas
- lipomas
- fibromas
- neurogenic tumours (neurofibroma & gangliocytic paraganglioma)
- Intermediate: NET, GIST
- Primary malignant (CALGary)
- NET 44% (variable behaviour) - most common tumour in ileum
- Adenocarcinoma 33% - most common malignancy in duo, decreases throughout rest of SB except in Crohn’s usu in ileum (70%)
- Stromal tumours 17% - can develop in entire SB
- GIST (variable behaviuor), leiomyosarcoma, liposarcoma
- Lymphoma 8%
- Secondary malignant
- direct extension (from colonic, gastric, pancreatic or renal)
- metastatic (melanoma, lung, breast, cervix, sarcoma, colon
2
Q
Risk factors for small bowel tumours
A
- congenital conditions
- FAP (duodenal adenomas & adenocarcinoma)
- HNPCC (adenocarcinomas throughout small bowel)
- Peutz-Jeghers (increased risk adenocarcinoma)
- Neurofibromatosis (leiomyosarcoma, adenocarcinoma, NET)
- Cystic fibrosis
- MEN1 assoc w NETs in rare cases
- acquired conditions
- chronic inflammation
- Crohn’s (100x increased risk of adenoca in areas affected w active disease)
- Coeliac disease (lymphoma & adenoca)
- Other imunodeficiency states (incl pts on biologic agents) (increased risk non-Hodgkin lymphoma after long-term immunosuppression)
- HIV: (lymphoma, Kaposi sarcoma)
- Radiation
- Smoking
- chronic inflammation
- pts w colon adenocarcinoma have higher risk of SB adenocarcinoma
3
Q
Management of small bowel adenocarcinoma
A
determined by location & stage
- R0 resection w locoregional LN resection = only curative tx
- consider neoadj chemo if invasion into adjacent structures then re-evaluate 2-3mo later
- non-infiltrating D1, D3, D4 tumour: can do duodenal resection if R0 resection possible
- D2 tumours: pancreaticoduodenectomy + regional lymphadenectomy of periduodenal, peripanc & hepatic LNs as well as resection of involved vascular structures
- Jej & ileal - resection & regional lymphadenectomy
- TI - ileocaecectomy & R hemi w ligation of ileocolic artery & subsequent regional lymphadenectomy
- currently no standard adjuvant protocol - most guidelines suggest consider if poorly differenitated or <10LNs; ?FOLFOX may increase OS in advanced disease
- metastatic disease - FOLFOX or FOLFIRI firstline
Prognosis poor, prob bc of delayed presentation & presence of advanced disease at dx
4
Q
What is the origin of small bowel neuroendocrine tumours?
A
Arise from enterochromaffin cells (considered neural crest cells) at the base of the crypts between intestinal villae
5
Q
How are neuroendocrine neoplasms classified?
A
- 2019 WHO histological grading scheme uses proliferative rate to startify the grades and requires both a mitotic count and the Ki-67 labeling index to be assessed; the higher of these two indices is used to define the final grade in cases where the mitotic rate and Ki-67 index are discordant
- Poorly differentiated histology and high tumour grade are no longer considered equivalent & while it is true that nearly all poorly differentiated NECs have a high proliferation rate, not all G3 tumours are poorly differentiated
- the most recent 2019 WHO classification of NENs recognises a category of high-grade (G3) well-differerentiated GEP NETs, & since poorly differentiated NECs are high grade by definition they are no longer assigned a grade
- NENs also categorised based on embryologic site of origin & secretory product
- foregut (resp tract, thymus)
- characteristically produce low levels of serotonin (5-hydroxytryptamine) but may secrete 5-hydroxytryptophan or ACTH
- midgut
- high serotonin production
- hindgut (distal colon, rectum)
- rarely produce serotonin but may produce other hormones eg somatostatin & peptide YY
- foregut (resp tract, thymus)
55% NETs from GI tract; 30% from bronchopulmonary system; rarer sites include kidneys or ovaries. Previously SB NETs most common (ileum), followed by rectum, appendix, colon and stomach; but since screening colonoscopy started, rectal NETs higher than SB NETs.
6
Q
Describe the pathological features of NETs
A
- on gross appearance, well-differentiated NETs of the tubular GIT are often well-circumscribed lesions in the submucosa or extending to the muscular layer/tend to infiltrate bowel wall & may extend through serosa, causing shortening & thickening of mesentery due to intense associated desmoplastic reaction
- (while those arising in pancreas may be well circumscribed, multinodular or infiltrative)
- cut surface appears red to tan, reflecting the abundant microvasulature, or sometimes yellow bc of high lipid content
- well-differentiated NETs show a solid, trabecular, gyriform or glandular pattern, solid nests of uniform small cells w fairly round or oval nuclei, coarsely stippled (‘salt and pepper’) chromatin, and finely granular cytoplasm; little or no cellular pleomorphism, hyperchromasia or increased mitotic activity
- poorly differentiated NECs are by definition high-grade carcinomas that resemble small cell carcinoma or large cell NEC of the lung - sheet-like or diffuse architecture, irregular nuclei & less cytoplasmic granularity
- NETs are characterised by production of biologically active amines, which are stored in neurosecretory granules; secretion of these products by tumour cells can result in variety of clinical syndromes
- most prominent agents secreted = serotonin & substance P; others include corticotropin, histamine, dopamine, neurotensin, prostaglandins, kinins, gastrin, somatostatin, pancreatic polypeptide, calcitonin
NB 30% of SB NETs have multiple synchronous nodules - check whole small bowel
7
Q
What is carcinoid syndrome?
A
- a term applied to constellation of sx mediated by various hormonal factors elaborated by some well-diff NETs of digestive tract & lungs which synthesise, store & release a variety of polypeptides, biogenic amines and prostaglandins
- >90% of pts w carcinoid have metastatic disease, typically to liver
- carcinoid syndrome affects <10% of pts w NETs
- primarily assoc w metastatic tumours originating in the midgut; hindgut and foregut NETs uncommonly produce carcinoid syndrome
- bc of firstpass metabolism of the vasoactive peptides responsible for carcinoid syndrome, hepatic mets or extra-abdo disease are necessary to elicit the syndrome
- classic description: vasomotor, cardiac, GI manifestations
- episodic attacks of cutaneous flushing, bronchospasm, diarrhoea & vasomotor collapse, also hepatomegaly & cardiac lesions most commonly right-sided heart valvular disease
- humoral factors considered to contribute include serotonin, 5-HT (precursor of serotonin), histamine, dopamine, tachykinin, kallikrein, substance P, prostaglandin & neuropeptide K
- carcinoid crisis = life-threatening form of carcinoid syndrome usu precipitated by a specific event eg aneasthesia, surgery or chemo
- manifestations include intense flush, diarrhoea, tachycardia, hyper/hypotension, bronchospasm, altered metnal status
- sx usu refractory to fluid resus & vasopressors
- other functioning NETs of SB that produce specific clinical syndromes = comparatively rare
- gastrinoma of duo - ZES (15% of gastrinomas in duo)
- rarer: duodenal somatostatinomas, paragangliomas, high-grade NECs (rarely functioning)
8
Q
What is the clinical presentation of small bowel NETs?
A
- most asymptomatic & incidental
- symptoms from mass effect
- intermittent obstruction secondary to intralumninal tumour, or from mesenteric kinking & distortion brought on by tumour invasion & a secondary desmoplastic response
- pain from vascular compromise secondary to large bulky mesenteric nodal mets or mesenteric vascular invasion +/- contribution from vasospastic effect of serotonin
9
Q
What is the typical CT appearance of a SB NET?
A
solid mass with spiculated borders & radiating surrounding strands associated with linear strands within the mesenteric fat and kinking of the bowel +/- regional lymph nodes
10
Q
How do you diagnose carcinoid syndrome?
A
- initial test = 24hr urinary 5-HIAA (the end product of serotonin metabolism)
- sens of >90%, spec of 90% for carcinoid syndrome; sensitivity low in pts w NETs w/o carcinoid syndrome
- generally most useful in pts w primary midgut NETs which produce highest levels of serotonin; foregut and hindgut tumours may produce 5-HT and histamine but no test for urinary 5-HT
- consider checking gastrin and VIP - some functional pancreatic neuroendocrine tumours can be assoc w severe diarrhoea
- chromogranin A has low specificity - not recommended as screening test for diagnosis of a NET or carcinoid syndrome; may be appropriate tumour biomarker for pts w established dx of advanced NET in order to assess disease progression
11
Q
Staging of small bowel NETs
A
- Duodenum & ampulla:
- T1 = mucosa or submucosa only, ≤1cm (duodenal) OR ≤1cm & confined within SOO (ampullary)
- T2 = invades muscularis propria or is >1cm (duodenal) OR invades through sphincter into duodenal submucosa or muscularis propria, or is >1cm (ampullary)
- T3 = invades pancreas or peripancreatic adipose tissue
- T4 = invades visceral peritoneum (serosa) or other organs
- N0 = no regional nodes; N1 = regional nodal involvement
- M1 = distant mets; M1a = mets confined to liver; M1b = mets in at least one extra hepatic site (eg lung, ovary, nonregional LN, peritoneum, bone); M1c = both hepatic & extrahepatic mets
- Stage 3 = T4 or N1
- Jejunum & ileum:
- T1 = invades lamina propria or submuocosa & is ≤1cm
- T2 = invades muscularis propria or >1cm in size
- T3 = invades through muscularis propria into subserosal tissue w/o penetration of overlying serosa
- T4 = invades visceral peritoneum (serosal) or other organs or adjacent structures
- N0 = no regional nodes; N1 = regional nodes <12; N2 = large mesenteric masses (>2cm) and/or extensive nodal deposits ≥12, espec those that encase superior mesenteric vessels
- M1 = distant mets; M1a = mets confined to liver; M1b = mets in at least one extra hepatic site (eg lung, ovary, nonregional LN, peritoneum, bone); M1c = both hepatic & extrahepatic mets (same)
- Stage 3 = involved nodes
12
Q
Management of SB NETs
A
- depends on tumour size, location & presence of metastatic disease
- <1cm diameter w/o evidence of regional LN mets: segmental intestinal resection
- >1cm with multiple tumours or w regional LN mets, regardless of size of primary tumour: wide excision of bowel & mesentery required
- lesions of TI = R hemi
- Small duo tumours can be excised locally but more extensive lesions may require pancreaticoduodenectomy
- lap is safe
- caution with anaesthesia: may precipitate carcinoid crisis characterised by hypotension, bronchospasm, flushing and tachyarrhythmias
- carcinoid crisis is treated w IV octreotide - bolus of 50-100ug, whihc may be continued as an infusion at 50ug/hr
- important to explore abdomen for multicentric lesions
- often a large desmoplastic rxn causing shortening, folding & pleating of SB mesentery resulting in intestinal angina & obstruction; in cases where mesenteric disease appears to involve a large portion of mesentery, appropriate to dissect tumour off mesenteric vessels, w preservation of blood supply to unaffected bowel
- extensive mobilisation of SB mesentery may be required
- removal of mesenteric disease provides significant survival advantage & ensures most durable palliation for the pt
- in pts w widespread metastatic disease, surgery may still be indicated bc definite role for surgical debulking which often provides beneficial symptomatic relief
- also improves survival & slows progression of liver mets
- liver mets may also be resected
- medical therapy
- somatostatin analogues (octreotide & lantreotide) - relieve sx of carcinoid syndrome & delay progression (though not all asymptmoatic pts treated initially)
- everolimus (mTOR inhibitor) - can slow progression
- others eg VEGF pathway inhibitors (sunitinib)
- poor response to chemo but streptozocin, 5-FU and cyclophosphamide or temozolomide +/- capecitabine or cisplatin & etoposide in poorly diff NECs
13
Q
What is required for a diagnosis of primary GI lymphoma?
A
- no peripheral or mediastinal lymphadenopathy
- normal WCC & differential on peripheral blood smear
- tumour involvement must be predominantly in GI tract
- no evidence of liver or spleen involvement
- primary GI lymphoma = most common extranodal form of lymphoma; stomach (25%) & SB most common sites
- risk factors: autoimmune diseases, immunodeficiency syndrome/drugs, Crohn disease, radiation therapy, nodular lymphoid hyperplasia
- in SB, most common in ileum bc arises from lymphoid aggregates in submucosa & ileum is lymphoid follicle-rich
Can be low or high grade and of B or T cel origin
- non-Hodgkin lymphomas
- B cell lymphomas that most often involve GI tract: MALT type, DLBC, mantle cell, Burkitt and Burkitt-like
- MALT occur most often in stomach; mantle cell in colon & SB
- T cell less common - most often jejunal
- B cell lymphomas that most often involve GI tract: MALT type, DLBC, mantle cell, Burkitt and Burkitt-like
- primary/secondary involvement of GI tract by Hodgkin lymphoma = v rare
14
Q
Causes of SBO
A
By frequency
- developed world: adheisons (60%), malignancy (20%, mostly peritoneal disease), hernias (10%), Crohn’s (5%), other (5%)
- developing world: hernia most common
By category
- Extraluminal
- adhesions
- congenital
- acquired - post-op, inflammatory, chemical (eg starch, talc)
- neoplastic
- peritoneal disease eg ovarian, pancreatic, gastric, colon
- extraintestinal neoplasms
- infection - eg diverticular abscess, TOA
- hernia
- primary
- inguinal, femoral
- paraduodenal, foramen of Winslow, diaphragmatic
- secondary
- incisional
- post-op internal hernia after bariatric surgery
- primary
- endometriosis
- adhesions
- Intraluminal - bezoar, food bolus, enterolith, gallstone, foreign body
- Mural
- inflammatory
- Crohn’s (acute flare or stenosis), TB, actinomycosis, eosinophilic gastroenteritis
- vasculitides eg scleroderma
- intussusception
- congenital
- duplication cyst
- malrotation/volvulus
- jejunal/ileal atresia
- neoplastic
- primary: NET, adenocarcinoma, GIST, lymphoma
- secondary
- trauma - haematoma
- iatrogenic
- post radiation stricture
- anastomotic stricture
- inflammatory
15
Q
Pathophysiology of SBO
A
- obstruction –> onset of vigorous SB peristalsis (both prox & distal to obstruction) to try & propel luminal contents past obstructing point –> colicky pain, usu in central abdo
- can account for sometimes initial diarrhoea
- later intestine becomes fatigued & dilates; contractions become less frequent & less intense
- proximal dilatation of intestine and with time, bowel wall becomes oedematous, with loss of normal absorptive function & fluid is sequestered into bowel lumen; this & fluid loss thorugh vomiting –> hypovolaemia
- loss of hydrogen & chloride ions –> alkalosis, hypochloraemia & hypokalaemia (from renal compensation)
- ischaemic necrosis of bowel most commonly caused by twisting of bowel and/or its mesentery around an adhesive band or intestinal attachments; alternatively if bowel dilation is excessive, as intraluminal pressure increases in bowel, venous pressure is eventually surpassed –> oedema & congestion –> intramural vessels of SB become compromised so perfusion to intestine reduced –> ischaemia –> necrosis and perforation if process not interrupted
- –> worsened, continuous (cf colicky) pain followed by perforation if left
- if blood supply remains intact & bowel decompressed by vomitign & NG drainage, peristalsis will stop & colicky pain ceases, leaving dilated, non-functioning bowel
- flora of SB changes dramatically in both type of organism (most commonly E coli, Strep faecalis & Klebsiella) & quantity increases markedly
- increased bacteria translocating to mesenteric LNs & even systemic organs
- bacterial translocation amplifies local inflammatory response in gut –> intestinal leakage & increased systemic inflammation +/- systemic sepsis & multiorgan failure
- other consequences of bowel obstruction include increased abdo pressure, decreased venous return & elevation of diaphragm, compromising ventilation
16
Q
Non-operative SBO management
A
- non-operative management is successful in 65-80% of pts w adhesive SBO
- gastrografin is a hypertonic water-soluble contrast that has both diagnostic & therapeutic properties
- draws fluid into lumen of bowel due to its hypertonicity, decreasing intestinal wall oedema & stimulating intestinal peristalsis
- identifies early pts who require surgery & those who dont’ thus reducing hospital stay & accelerating resolution of SBO in pts who would have resolved w/o surgery, but doesn’t reduce need for surgical intervention
- contraindicated in pregnancy, presence of bowel compromise & has only been studied in pts w adhesive SBO therefore shouldn’t be given to pts w nonadhesive causes
- aspirate to dryness, 100mL undiluted GG, clamp for 2-4hrs, AXR in 6-24hrs at convenient time
- radiological appearance of contrast in colon within 24hrs predicts resolution in 99% of pts
- failure of contrast to reach colon 24hrs later should influence but not dictate decision to operate; signif % of pts may require longer duration of nonop mx for successful resolution; most would wait up to 3-5days before operating (though stable pts w known frozen abdomens/other complicating factors may be observed for longer +/- w PN
- pathologies other than adhesions that warrant trial of non-op mx:
- inflammatory bowel disease - medical mx
- infections SB disease eg TB - medical mx
- colonic diverticulitis
- radiation enteritis - higher risk of anastomotic leak so best avoid surgery
- malignant obstruction
17
Q
Options for malignant SBO
A
- remember some are from adhesions not malignancy
- no consensus/evidence re optimal strategy
- weight risks & benefits, life expectancy, goals of care
- medical mx - fluid diet, steroids, NG, PEG
- surgical mx - resection, bypass, stoma, bail
18
Q
Management of small bowel radiation enteritis
A
- can present w acute abdomen during radiotherapy due to radiation enteritis or w acute-on-chronic attack many yrs later
- if obstruction from fibrosis from prev radiotherapy: prolonged non-op mx even w IVN may be preferable to surgery - adhesions often dense & if SB injured, signif risk it might not heal whether repaired or anastomosed
- if anastomosis necessary, should only anastomose irradiated bowel to non-irradiated bowel
19
Q
Incidence of small bowel diverticular disease (excluding Meckel’s)
A
- most common in 6th & 7th decades
- symptomatic diverticula most common in duo (79%); jejunum or ileum in 18%; all 3 in 3%
- 60% also have colonic diverticula
- duodenal relatively common - 20% in autopsies
- rare <40yrs
- most common duo location is near ampulla
- jejunoileal diverticula much more rare; 0.1-1.5% in autopsies
- usually mulitple & localised to prox jejunum; distal jej & ileum less frequently affected
- mainly in 60s+, often have connective tissue disorders
*
20
Q
Classificaiton of small bowel diverticular disease
A
- congenital vs acquired
- congenital - Meckel and intraluminal
- intrluminal vs extraluminal
- true vs false
- true = all 3 coats of bowel present in wall of diverticulum (Meckel)
- false = wall lacks proper muscle coat - mucosa & submucosa protrude througha. defect in muscle coat
- extraluminal duodenal diverticula
- most jejunoileal diverticula
- by location - duodenal, jejunal, acquired
Vast majority are extraluminal and acquired
21
Q
Aetiology of small bowel diverticula
A
Duodenal
- extraluminal (most common) = false (acquired as a result of herniation through a defect caused by entrance of large vessels supplying bowel wall
- combo of increased intraluminal pressures & intrinsic weakness of muscular layer thought to play a role
- diverticula that are juxtapapillary/periampullary (located 2-3cm adjacent to ampulla) = assoc w inc risk of choledocholithiasis w bilirugin-containing pigment stones (also pancreatitis); poss mechanisms:
- primary intraductal stones from biliary stasis due to extrinsic CBD compression
- duo content reflux through incompetent SOO
- stasis-assoc bacterial contamination of CBD allowing deconjugation of bilirubin glucuronide & precipitation of bile salts
- intraluminal = ‘windsock diverticula’ - result from incomplete canalisation of foregut, producing duodenal diaphragm or web during embryonic development
- lined on both sides w duo mucosa, and an eccentric opening is usu proximal in the sac
Jejunoileal
- usu false (mucosa & submucosa only)
- aetiology unclear but intestinal dysmotility & high intraluminal pressures thought to play a role; freqeuntly assoc w intestinal dysmotility conditions eg progressive systemic sclerosis, visceral neuropathies & myopathies
- protrusion of mucosa through defects in lamina muscularis mucosae, where vasa recta penetrate bowel wall –> diverticula on mesenteric side of bowel
- (Meckel - covered elsewhere - true diverticula on antimesenteric side)
