Small bowel Flashcards
What is your framework for considering small bowel tumours
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
Risk factors for small bowel tumours
- 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
Management of small bowel adenocarcinoma
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
What is the origin of small bowel neuroendocrine tumours?
Arise from enterochromaffin cells (considered neural crest cells) at the base of the crypts between intestinal villae
How are neuroendocrine neoplasms classified?
- 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.
Describe the pathological features of NETs
- 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
What is carcinoid syndrome?
- 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)
What is the clinical presentation of small bowel NETs?
- 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
What is the typical CT appearance of a SB NET?
solid mass with spiculated borders & radiating surrounding strands associated with linear strands within the mesenteric fat and kinking of the bowel +/- regional lymph nodes
How do you diagnose carcinoid syndrome?
- 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
Staging of small bowel NETs
- 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
Management of SB NETs
- 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
What is required for a diagnosis of primary GI lymphoma?
- 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
Causes of SBO
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
Pathophysiology of SBO
- 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
Non-operative SBO management
- 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
Options for malignant SBO
- 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
Management of small bowel radiation enteritis
- 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
Incidence of small bowel diverticular disease (excluding Meckel’s)
- 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
*
Classificaiton of small bowel diverticular disease
- 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
Aetiology of small bowel diverticula
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)