Appendix

Question 1

Discuss the embryology and anatomy of the appendix

Answer 1

• midgut organ, first identified at 8wks gestation as a small outpouching of the caecum
• as gestation proceeds, appendix becomes more elongated & tubular as the caecum rotates medially & becomes fixed in the RLQ
• agenesis of appendix + duplication & even triplication reported
• variable size (5-35cm) but averages 9cm length in adults
• base lies at convergence of taenia
• unequal growth of saculated caecum during childhood (R side enlarges more rapidly) –> appendix lies medially & posteriorly
• variable position of tip:
  
  • retrocaecal (but intraperitoneal) 60%
  • pelvic 30%
  • retroperitoneal 7-10%
• appendiceal artery (end artery) = usu off inf division of ileocolic –> mesoappendix
• mesoappendix also contains lymphatics of appendix which drain to ileocaecal nodes, along blood supply from SMA
• bloodless fold of Treves - rins between ileum & mesoappendix (sapce under it is inferior ileocaecal recess

Question 2

What is the management of incidental appendiceal NETs?

Answer 2

• tumours ≤1cm with clear resection margins, mesoappendiceal invasion <3mm, absence of angio or neuroinvasion and Ki67 <3% = appendiectomy only
• tumours 1-2cm, positive/unclear margins, mesoappendiceal invasion >3cmm, LVI, G2 proliferation rate (Ki67 3-20%) = consider right hemi
• tumours >2cm or G3 proliferation rate (Ki67>20%) = right hemi

Question 3

What are goblet cell carcinomas of the appendix and how are they classified?

Answer 3

Type of adenocarcinoma showing combined mucinous & neuroendocrine differentiation.

Tang classification (A, B, C)

Considered more aggressive than other NETs, could behave more like appendiceal adenocarcinomas in terms of LN involvement, chance of peritoneal spread & prognosis - treat as adenocarcinomas; most guidelines say right hemi for all. If perforated w/o evidence of peritoneal spread CONSIDER adjuvant CRS and HIPEC. IF evidence of peritoneal spread deeemed resectable, adjuvant CRS & HIPEC should ALWAYS BE DONE.

Question 4

How are incidental appendiceal LAMNs (found on histo) managed?

Answer 4

• no need for right hemi - appendicectomy sufficient
• if cellular or acellular mucin, regardless of whether perforated or not, with no postop rad/biochemical signs of residual disease, can consider adjuvant CRS and HIPEC

ANZJS Soucisse et al:

• type I LAMNs, completely resected: low risk for recurrence, f/u
• if positive margins or type 2 LAMNs (characterised by leakage of mucus thorugh appendix wall) - consider abdominal exploration with prophylactic HIPEC

Question 5

How are incidental HAMNs of the appendix (found on histo) managed?

Answer 5

• if nonperforated pT<4,Nx,M0,R0 and no postop rad/biochem signs of residual disease, CAN CONSIDER adjuvant right sided hemi & CRS & HIPEC
• if perforated or M1b, DO R HEMI & CRS & HPEC

Question 6

What is the management of an incidental appendiceal mucinous adenocarcinoma (found on histo)?

And a nonmucinous adenocarcinoma?

Answer 6

Mucinous adenocarcinoma:

• adjuvant right hemi always done +/- consider adding CRS and HIPEC especially if T4, perforated or if resection margins positive
• ?systemic chemo for stage III and high risk stage II as for nonmucinous adenocarcinoma

Nonmucinous adenocarcinoma:

• right hemi + systemic chemo if stage III or stage II w high risk features

Question 7

What are the contraindications to CRS and HIPEC in appendiceal PMP?

Answer 7

• Absolute
  
  • extensive SB serosal involvement, where not possible to leave ≥1.5-2m of SB
  • mesenteric involvement causing retraction
• Relative
  
  • age >75yrs
  • aggressive histo w PCI >20
  • involvement of liver hilum
  • infiltration of anterior pancreatic surface
  • ureteric obstruction
  • need for complete gastric resection
• in pts w appendiceal PMP who aren’t fit for a major procedure and/or have unresectable disease, or if they have resectable disease but negative prognostic factors (high grade, signet ring cell histo), maximal tumour debulking (greater omentectomy, lower abdominal peritonectomies & an extended right hemicolectomy +/- bilateral oophorectomy) +/- HIPEC can be considered

Question 8

What does CRS and HIPEC involve?

Answer 8

Cytoreductive surgery

• evaluate for any contraindications eg extensive SB serosal involvement, mesenteric disease compromising SB viability, heavy porta hepatis involvement, extensive retroperitoneal nodal disease or extensive liver mets
• excise peritoneum - sometimes all
• omentectomy routinely done & heavily involved organs excised - common resections include right hemi, anterior resection, splenectomy and segmental SB resections

HIPEC

• when complete or near complete cytoreduction obtained (ie all tumour nodules >0.25cm removed), HIPEC added to treat microscopic residual tumour cells
• depending on chemo agent & histo, tissue penetration into tumour nodules is 2-3mm
• heating the chemo enhances effect while having a direct cytotoxic effect on neoplastic cells
• different protocols; range from 30-90mins, most use Mitomycin C or oxaliplatin

Question 9

Classification for appendiceal neoplasms

Answer 9

• epithelial neoplasms
  
  • nonneoplastic mucinous (mucocele)
  • mucinous epithelial neoplasms
    
    • serrated polyp of appendix, w or w/o dysplasia
    • LAMN
    • HAMN
    • mucinous adenocarcinoma, w or w/o signet ring cells
  • nonmucinous epithelial neoplasms
    
    • adenoma
    • adenocarcinoma, w or w/o signet ring cells
  • epithelial neoplasms with neuroendocrine features
    
    • neuroendcrine tumour
    • goblet cell carcinoma
• other neoplasms
  
  • metastases
  • mesenchymal eg GIST, lymphoma, granular cell tumour

Question 10

How is PMP classified?

Answer 10

PSOGI/Sugarbaker

• PMP
  
  • acellular mucin
  • low-grade mucinous carcinoma peritonei (M1b G1 / DPAM)
  • high-grade mucinous carcinoma peritonei
    
    • well, moderately, poorly differentiated
    • (M1b G2 or G3 / PMCA-I / moderately or poorly differentated PMCA)
  • high-grade mucinous carcinoma peritonei with signet ring cells
    
    • poorly differentiated
    • (M1b G3 / PMCA-S)
• Peritoneal carcinomatosis

Ronnett

• Disseminated peritoneal adenomucinosis (DPAM)
• PMCA-I (well differentiated peritoneal mucinous carcinomatosis)
• PMCA (moderately or poorly differentiated)
• PMCA-S (poorly differentiated with signet ring cells)

Question 11

What is pseudomyxoma peritonei?

What is the pathophysiology of PMP?

Answer 11

PMP is a clinical condition characterized by diffuse collections of gelatinous material in the abdomen and pelvis, and mucinous implants on the peritoneal surfaces. It is not a histologically based term and is not used in the staging or histological classification of appendiceal neoplasms.

Mucinous appendiceal neoplasms are the leading cause of PMP and it can also be caused by mucinous adenocarcinomas and goblet cell tumours. Peritoneal seeding of all other appendiceal lesions = peritoneal metastases. PMP can also be caused by mucin-producing invasive adenocarcinomas of the large/small bowel, lung, breast, pancreas, stomach, bile ducts, GB & fallopian tubes/ovary.

Appendiceal PMP = a clinical entity that incorporates 2 malignant components; the appendix primary and secondary peritoneal disease - both have individual histo subclassification, sometimes with discordance.

In MANs, as the tumor grows and occludes the lumen, mucus accumulates, and the appendix ruptures. The peritoneum is then seeded with mucus-producing cells, which continue to proliferate and produce mucus. The progressive accumulation of copious amounts of mucinous fluid gradually fills the peritoneal cavity, resulting in the characteristic “jelly belly”.

Question 12

What are the two eponymous signs associated with appendicitis in pregnancy?

Answer 12

1. Adler’s sign - shifting tenderness suggests tubo-ovarian pathology rather than appendicits
2. Bryan’s sign - pain when uterus is shifted to the right.

Question 13

Classify appendiceal neoplasms

Answer 13

• Neuroendocrine tumours (“Carcinoid”)
  
  • 50%
• Epithelial tumours
  
  • Mucinous
    
    • Mucinous adenoma
    • Low grade appendiceal mucinous neoplasm
    • Mucinous adenocarcinoma
  • Non-mucinous
    
    • Goblet cell carcinoma (“adenocarcinoid”)
    • Intestinal type adenocarcinoma
    • Signet ring cell adenomcarcinoma

Question 14

What is the argument for early use of MRI in pregnant patients where concerns of appendicitis exist?

Answer 14

• Foetal loss in complicated appendicitis is ~6% (2% in early)
• Foetal loss in negative appendicectomy is ~4%
• Pre-term labour in complicated appendicitis is ~11% (6% in early)
• Pre-term labour in negative appendicectomy is ~10%
• Atypical presentations of appendicitis are present ~50% of the time in pregnant patients.
• Ultrasound accuracy is reduced in pregnancy - 78% sens, 83% spec
• MRI has halved the negative appendicectomy rate w/o a significant increase in perforation rate, and has been shown to be cost effective
• if MRI not available, surgery
• Some recommend CT - associated with 8% negative appendicectomy rate cf 32% by clinical assessment & USS combined
  
  • these authors argued the amount of radiation delivered during a limited CT is below threshold required to induce fetal malformations & that most cases of appendicitis in pregnancy occur in 2nd or 3rd trimester, when organogenesis is already complete

Question 15

Discuss imaging in appendicitis.

When do you do a CT to diagnose appendicitis?

Answer 15

• USS: sens 80%, spec 88% - high spec when positive but can’t exclude appendicitis
  
  • >7mm = abnormal, bullseye appearance, on-compressible tender structure in RIF
  • most useful in children or pregnancy
• CT: sens 95%, spec 99%
  
  • thick-walled, >7mm diameter, mural enhancement, target sign/bullseye appearance, periappendiceal fat stranding +/- fluid/air if perf
• MRI: sens 100%, spec 98%
  
  • reserved for pregnancy mainly, done w/o contrast
  • >7mm, thickening >2mm, presence of inflammation
• a recent meta-analysis concluded CT is increasing in use and has reduced negative appendiectomy rates; proposed routine use of CT in adult pts
• I would request a CT if:
  
  • there are other causes for RIF pain felt to be genuinely competitive w appendicitis as the diagnosis, eg sigmoid diverticulitis
  • there is a history and exam consistent w appendix abscess or phlegmon, which may dictate non-op mx w PCI and delayed appendicectomy
  • there is a mass
  • typically used in older patients (>50) to confirm the diagnosis prior to surgery

Question 16

What is the evidence around lap vs open appendicectomy?

Do you take the mesoappendix?

Answer 16

A 2017 systemic review and meta-analysis of two trials and 14 retrospective studies of perforated appendicitis showed that, compared w open surgery, lap reduced the risk of SSI, length of hospital stay & time to oral intake w/o increasing the rate of intra-abdominal abscess. Operating time was slightly longer lap but only by 14 minutes.

A separate systematic review and pooled analysis also found laparoscopic appendectomy to be associated with fewer short-term and long-term adhesive bowel obstructions (OR 0.43 and 0.3)

I usually perform meso-appendicectomy, though this is dependent on the morphology of the appendicitis. Some advocate for routine mesoappendicectomy in case of an incidental finding of a neuroendocrine tumour however for every 1000 appendicectomies, a neuroendocrine tumour is found in 10, and in 1-2 of those 10 (ie 1-2 out of 1000) a right hemi would be avoided if mesoappendicectomy had been formed at time of index operation.

Question 17

What is the pathogenesis of appendicitis?

Answer 17

3 common aetiological hypotheses

1. Mechanical/obstructive
   
   • lumen is obstructed by lymphoid aggregates within appendix wall (60%), faecolith (35%), FB eg worms, veg seeds, cherry stones (4%), tumours of caecum/appendix (1%)
   • lower incidence of appendicitis in pops with high-fibre diet (less likely to form faecoliths)
   • obstruction of prox appendix –> increased pressure in distal portion bc of ongoign mucus secretion & gas production by bacteria in lumen –> progressive distension = impaired venous drainage & mucosal ischaemia; continued obstruction gives full thickness ischaemia –> perforation
2. Infective
   
   • draws on findings that viruses eg dengue, influenza, EBV, rotavirus, CMV & bacteria like campylobacter, salmonella, and parasites like entamoeba histolytica, Shistosoma - have been isolated in specimens or indirectly implicated in pathogenesis
   • thought to cause it by invading lamina propria & initiating oedematous obstruction of the narrow lumen
3. Hygiene
   
   • because there was an incidence of appendicitis in Britain from 1895-1930 before declining; thought that increase was due to better housing & sanitation which resulted in compromised GI immune system

Question 18

Incisions for open appendicectomy

Answer 18

• McBurney/Gridiron
  
  • oblique, muscle-splitting incision at McBurney’s point (2/3 from umbo to ASIS), perpendicular to line between umbo & ASIS
  • 5-8cm long, 1/3 above the line, 2/3 below
  • if necessary, the external oblique muscle & aponeurosis can be split in both directions and the int oblique & transversus muscles can be cut to convert incision into a right-sided Rutherford Morrison incision
• Lanz
  
  • RLQ skin crease, still through McBurney’s point, ends up below bikini line?
• Rockey-Davis
  
  • RLQ transverse incision, centered over McBurney’s point/point of max tenderness
• Lower midline

Question 19

What is the evidence around antibiotics as a primary treatment option for appendicitis?

Answer 19

Antibiotic therapy has been proposed as an alternative to surgery for uncomplicated appendicitis. In 2020, the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial reported that the 30-day general health status of patients treated with antibiotics was comparable to the appendectomy group; however, 29% of medically-treated patients required appendectomy by 90 days.

Longer-term data from this trial now confirm high rates of subsequent appendectomy after initial medical therapy: 40% at one year, 46% at two years, and 49% at three and four years. Given these high appendectomy rates, we continue to suggest surgery for uncomplicated appendicitis and reserve antibiotic therapy for those who are medically unfit for or decline surgery.

Question 20

Arguments for and against removal of normal appendix at diagnostic laparoscopy

Answer 20

• If appendix normal + alternative dx eg PID or diverticulitis is found, surgical judgement should be used (usually easy & probably best to remove but may not be the case if alternative pathology is complex eg perforated peptic ulcer, severe diverticulitis or malignancy
• If no other pathology, arguments for removing appendix are
  
  • Small incidence of appendicitis on histo exam of a macroscopically normal appendix – study investigating ability of laparoscopy to discriminate between a normal & inflamed appendix demonstrated a sensitivity of 92% & spec of 85% if an appendix w isolated mucosal inflammation was considered to be inflamed
  • Other pathologies may be detected (eg adenomas, carcinoid)
  • Removal of appendix prevents dx dilemma in future in a pt w persistent abdo sx following laparoscopy
• Against
  
  • questionable clinical significance of isolated mucosal inflammation in an otherwise normal appendix, & all operations are associated w some risk, however small (?6% in appendicectomy)
• If Crohn’s disease found: remove appendix anyway, provided caecal base is healthy, as avoids dx doubt in future

Incidental appendicectomy - ie removed at the time of an unrelated procedure

• theoretical benefit = eliminating risk of future appendicitis
• but has increased morbidity & mortality and been shown to not be cost-effective as a preventive measure
• recent finding that appendix may actually have a role in maintenance of healthy colonic flora

Question 21

How do you manage patients with an appendix abscess/phlegmon who are initially managed non-operatively?

Answer 21

• antibiotics +/- perc drain
  
  • 2010 meta-analysis showed that initial non-op mx of perforated appendicitis with abscess or phlegmon is associated w fewer complications & similar length of stay and antibiotics
  • a subsequent small randomised trial showed immediate lap appendix feasible & resulted in fewer readmissions and additional interventions, but 10% required bowel resection, 10% conversion to open & 13% had incomplete appendicectomy
  • >80% of pts w contained perforation can be spared appendiectomy during initial admission
• pts >40 who have not had recent colonoscopy should be offered this to check for caecal/appendiceal neoplasm
• role of routine interval appendicectomy is controversial and there have been no large-scale RCTs about the outcomes of pts who do or don’t undergo interval appendicectomy after successful non-op tx
  
  • For:
    
    • 10-29% of interval appendicectomy specimens have a neoplasm
    • 2019 Finnish trial was terminated early; in 60 pts, 20% overall incidence of neoplasms & 29% in those >40yrs
    • also avoids recurrent appendicitis (occurs in 5-38%) but this is not the reason
  • Against
    
    • others argue that cancer can be ruled out with colonoscopy & interval CT so interval appendicectomy not required
    • also in majority ‘appendix has been destroyed’ & in one study only 9% pts treated non-op got recurrence symptoms within 5mo (in another 20% within 3yrs)
    • some offer if faecolith on CT - predictive of higher risk of recurrent appendicectomy
    • more cost effective to offer selective
    • complications 3.4%

Question 22

What are the CT findings in appendiceal PMP?

Answer 22

• mucin = similar denisty to water, heterogenous.
• scalloping of liver, spleen & mesentery, calcifications common
• undersurface of diaphragm may be greatly thickened by large cystic masses of mucinous tumour
• early finding = peripheral location of tumour within abdomen & pelvis with relative sparing & central displacement of SB & mesentery (‘redistribution phenomenon’
• presence of tumour nodules >5cm on jejunum, proximal ileum or adjacent mesentery = more consistent w peritoneal mucinous carcinomatousis; also the presence of segmental SBO
• CT scoring systems exist

Question 23

How is PMP quantitatively assessed?

Answer 23

Peritoneal cancer index (most commonly assessed at laparoscopy

• a grading system for PMP that predicts likelihood of complete cytoreduction & correlates with survival
• abdomen is divided into 13 areas; 9 abdo/pelvis and 4 x SB
• lesion size scored according to size
  
  • 0 = no visible tumour
  • 3 = >5cm
  • total score = 0-39

Question 24

What is the treatment approach for pseudomyxoma peritonei?

Answer 24

Most cases are treated with periodic surgical de-bulking though there are a small subset of patients who may achieve long-term remission or even cure with surgery + HIPEC.

Prognosis depends on the tumour of origin and where the PMP sits on the histopathological spectrum of disease from DPAM to PMC.