Reproductive Aspects of Acute Appendicitis

Posted by Professor Mike O’Connor AM on 26 July 2018
Reproductive Aspects of Acute Appendicitis

Introduction

Appendicitis most often occurs between the ages of 10 19 years, with an incidence of between 19-28 per 10,000 before the age of 14 years. Less than 7 per 10,000 children present with appendicitis before the age of 4 years & less than 5% of presentations with appendicitis occur before the age of 5 years. 

Causation 

In tropical climates the cause is often a parasitic worm (pinworm or roundworm) causing obstruction whereas in temperate climates the cause of obstruction of the appendix is more likely to be mechanical twisting or lymphoid hyperplasia associated with viruses such as adenovirus and rubeola or an endoluminal faecolith or undigested food. Periumbilical pain signifies appendiceal colic associated with the obstruction.

As part of the obstruction the lumen of the appendix increases in diameter and this is the basis of the ultrasonic diagnosis of appendicitis: the diameter exceeds 6 mm.

The proliferation of bacteria results in penetration of the wall of the appendix which becomes inflamed and gangrenous. When the pain moves to the right iliac fossa and becomes constant then inflammation of the appendix is underway. Perforation occurs rarely in the first 12 hours of symptoms but is more likely with time thereafter, becoming common after 72 hours. 

Generalized peritonitis develops if the infection is not contained by bowel loops and omentum.

Delays in Diagnosis in Young Girls

Prior to rupture there appears to be no effect of appendicitis on tubal function however when the diagnosis is delayed and perforation has already occurred at the time of surgery tubal damage is increased (Relative Risk =4.8;95% CI =1.5-
14.9).

Future Risk of Ectopic Pregnancy

There appears to be a significantly increased risk of ectopic pregnancy in women who have appendicitis. In one study Elraiyah et al found the risk to be (OR=1.78,95% CI=1.46-2.16). A study by Fernandez et al found a similar increase in the risk of ectopic (RR= 2.2 ;95 percent CI: 1.5-3.2 ) but there appeared to be no difference in the ectopic rate between ruptured and unruptured appendices.

Appendicitis in Pregnancy

In a classic case of appendicitis in pregnancy Tthe pain is periumbilical & colicky initially and then migrates to the right lower quadrant as a constant pain as the inflammatory process progresses Anorexia, nausea and vomiting, if present, follow the onset of pain. Fever up to 38.3ºC and leukocytosis develop later. Many patients have a nonclassical presentation, with symptoms such as heartburn, bowel irregularity, flatulence, malaise, or diarrhea. If the appendix is retrocecal, patients often complain of a dull ache in the right lower quadrant rather than localized tenderness. Rectal or vaginal examination in such patients is more likely to elicit pain than abdominal examination. A pelvic appendix can cause tenderness below McBurney's point. The most common symptom of appendicitis, ie, right lower quadrant pain, occurs close to McBurney's point in the majority of pregnant women, regardless of the stage of pregnancy however, the location of the appendix migrates a few centimeters cephalad with the enlarging uterus, so in the third trimester, pain may localize to the mid or even the upper right side of the abdomen (see figures)

   

Investigations

  1. WCC. Approximately 80 percent of nonpregnant patients with appendicitis have a preoperative leukocytosis (white cells >10,000 cells/microL) and a left shift in the differential. However, mild leukocytosis can be a normal finding in pregnant women: the total leukocyte count may be as high as 16,900 cell/microL in the third trimester.
  2. Ultrasound of Appendix. The initial modality of choice for diagnostic imaging of the appendix in pregnancy is graded compression ultrasonography. The clinical diagnosis of suspected appendicitis is supported by identification of a non-compressible blind-ended tubular structure in the right lower quadrant with a maximal diameter greater than 6 mm.
  3. MRI .For pregnant women whose ultrasound examination is inconclusive for appendicitis, magnetic resonance imaging (MRI) is the preferred next test as it avoids the ionizing radiation of computed tomography and appears to be cost-effective

Obstetric Consequences of Acute Appendicitis in Pregnancy

The main complication is threatened preterm labour. In one study contractions occurred in 83% of all appendicitis patients in pregnancy >24 weeks with 13% exhibiting changes in cervical dilatation. The advent of laparoscopic appendicectomy has encouraged earlier diagnosis and treatment. Delayed diagnosis can have dire adverse effects on the fetus due to prolonged sepsis.

Further Reading

  1. Mueller BA et al.Appendicectomy and the risk of tubal infertility. NEJM 1986.315:1506-1508
  2. Elraiyah T et al. The effect of appendectomy in future tubal infertility and ectopic pregnancy: a systematic review and meta-analysis. J Surg Res 2014.192(2)368-374
  3. Fernandez et al. Appendectomy, a risk factor for ectopic pregnancy La Presse Medicale 1992 21(39):1859-1861.
  4. Williams R, Shaw J Ultrasound scanning in the diagnosis of acute appendicitis in pregnancy. Emerg Med J. 2007 May;24(5):359-60
Posted in: Obstetrcis Ultrasound Other  

NIPT screening & Nuchal Translucency - Complimentary rather than alternatives

Posted by Professor Mike O’Connor AM on 2 May 2018

The advent of the Non Invasive Prenatal Test has been a major advance for the detection of Trisomy 21 (Down s.), Trisomy 18 (Edwards s.) & Trisomy 13 (Patau s.) and reduces the need for invasive tests which have up to a 3% risk of miscarriage.

There has been a subsequent tendency to abandon the previous nuchal translucency ultrasound and biochemical test because of the increased accuracy of detection of the trisomies with the NIPT test which can detect 99% of Down syndrome fetuses c.f. a 90% detection rate with NT Plus.

What seems to be less well appreciated is that the NIPT does not provide a full karyotype as it relies on frag-ments of fetal DNA within maternal blood .These are then used to detect T211,T18 or T13 using specific probes. More recently a further probe is availa-ble to detect 22 q deletions as found in DiGeorge syndrome: a complex syndrome involving cardiac ,facial, skeletal and neurological abnormalities which has an incidence of 1/1000.

Reliance on an NIPT to exclude a fetal aneuploidy is unsound and a positive NIPT will still require confirmation using genetic amniocentesis or CVS. The value of a nuchal translucency test between 11-13 weeks is that it will give additional information not available with an NIPT test.

For example, the nuchal translucency is not just increased (>3 mm) in fetal aneuploidies such as Down syndrome and Turner's syndrome (45 XO) but is also increased in fetal cardiac malformations: more than 55% of all major congenital heart defects in one series (Hyett et al 1999) had an NT > 95 per-centile (NR 1.8-2.35 mm) and the negative predictive value of a normal NT was 99.9%.

Furthermore a careful ultrasound scan at 11-13 weeks can give additional information such as cervical length ( values <3 cm can predict cer-vical incompetence) as well as basic information such as cranial anatomy (eg excluding anencephaly), spine, stomach, kidneys, bladder & presence of all 4 limbs. These non-cardiac features can be reasonably assessed in between 75-98% of cases between 11-14 weeks. Other important ultrasound findings at 11-13 weeks include detection of uterine fibroids and ovarian tumours which may cause complications such as red degeneration and torsion respectively later in pregnancy.

Fetal morphology scans: diagnostic value and limitations especially fetal heart anomalies

The fetal morphology scan is normally performed between 18-20 weeks gestation. If performed by skilled ultrasonologists it will detect a significant number of serious fetal anomalies. It is important to remember that only about one third of structural abnormalities are associated with an abnormal karyotype. The basic information available includes:

  1. An assessment of gestational age (+/- 7-10 days error)
  2. An assessment of fetal morphology
  3. An assessment of placental localization (bearing in mind that the vast majority of 'low lying' placentae will not remain so by term)

Approximately 1% of liveborn fetuses have congenital heart disease (CHD). What is concerning is the failure to diagnose a large number of these fetuses with (CHD) at that gestational age. A little later at 22 weeks there is a better yield of diagnoses of CHD.

The 1993 RADIUS study surveyed 92 obstetric practices and 17 family practices in 6 US States and identified 15,530 low risk pregnant women who were scanned between 15-22 weeks and 31-35 weeks by 28 ultrasound referral laboratories staffed by 91 qualified sonologists. Of those women (whose fetal anomaly rate was 2.3%) only one third had one (or more) major fetal anomalies detected by 24 weeks. It demonstrated that few of the CHD's were detected .No improvement in overall perinatal outcome could be demonstrated. 

More recently one US study (Pinto et al, 2011) over a 10 year period found that only only 39% of 1474 cases of significant CHD were detected, with no improvement in detection rate over the 10year period. Detailed fetal echocardiography can improve the detection rate but this is impractical for large populations. The 4 chamber cardiac scan is the basic standard and this will miss defects such as transposition of the great arteries (TGA), tetralogy of Fallot (TOF), double-outlet right ventricle (DORV) and truncus arteriosus. The 4 chamber view cardiac view is likely to identify complete atrioventricular septal defect (AVSD), congenitally corrected transposition of the great arteries (CCTGA), tricuspid valve disease (including Ebstein's anomaly) and all single ventricle defects including hypoplastic left heart syndrome (HLHS). A circumspect approach is therefore required when receiving a normal fetal morphology scan result.

Further reading:

  • Alldred SK et al. First trimester ultrasound tests alone or in combination with first trimester serum tests for Down's syndrome screening.Cochrane Database Syst Rev. 2017 Mar 15;3:CD012600. doi: 10.1002/14651858.CD012600.
  • Sharifzadeh M et al. Normal reference range of fetal nuchal translucency thickness in pregnant women in the first trimester, one center study J Res Med Sci. 2015 Oct; 20(10): 969973.
  • Hyett J,Perdu M,Sharland G, Snijders R,Nicolaides K. Using fetal nuchal translucency to screen for major congenital cardiac defects at 10-14 weeks of gestation: population based cohort study BMJ. 1999 Jan 9; 318(7176): 8185.
  • Pinto NM et al. Barriers to prenatal detection of congenital heart disease: a populationbased study Ultrasound Obstet Gynecol. 2012 Oct;40(4):418-25. doi: 10.1002/uog.10116. Epub 2012 Sep 17.
  • Ewigman BG et al. Effect of prenatal ultrasound screening on perinatal outcome. RADIUS Study Group.N Engl J Med. 1993 Sep 16;329(12):821-7.
Posted in: Obstetrcis Ultrasound Miscarriage  

Women's Health Screening _Quo Vadis?

Posted by Professor Mike O’Connor AM on 15 February 2018

The recent Federal Government decision to rebate cervical cancer screening only every 5 years and to only rebate for screening after the age of 24 years and under the age of 74 years raises the question as to whether other aspects of women's health could be also screened far less frequently. That could be an unintended negative consequence of the recent Government funding decision. 

The chance of an Australian woman being diagnosed with a gynaecological cancer by age 85 is 1:5. At its best a well women's check not only screens for cervical cancer (1% incidence) but also for:

  • Breast cancer (1:8 or 12%)
  • Uterine cancer (2.5%)
  • Ovarian cancer (1.8%)
  • Vulval cancer (0.1%)
  • Benign ovarian tumours and cysts
  • Lichen sclerosis (0.3%) of whom 4% develop vulval cancer
  • Uterine fibroids (40% >aet 40)
  • Utero-vaginal prolapse (25%)
  • Urinary incontinence (37%)
  • Anal incontinence (12.9%)
  • Severe menopausal symptoms (22%)
  • Osteoporosis (20%> aet 50)

The value of early diagnosis is in improving survival rates. The survival from most gynaecological cancers is stage dependent:

  • Cervical Cancer: Progresses at a rate of - 1 Grade per annum. The 5 yr survival rate by the stage of the cancer approaches 93% for stage 1A, 80% for Stage 1B, 63% for stage 2A, 35% for stage 3A, 16% for stage 4A.
  • Uterine cancer: The 5 yr survival rate by the stage of the cancer approaches 85% for stage I, 75% for stage II, 45% for stage III and 25% for stage IV.
  • Ovarian Cancer: The 5 yr survival rate by the stage of the epithelial cancer approaches 90% for stage 1; 70% for stage 2; 39% for stage 3; 17% for stage 4. Unfortunately most ovarian cancers are diagnosed at a late stage. A current view is that many ovarian cancers arise from Fallopian tubes - hence the new emphasis on salpingectomy at hysterectomy.
  • Vulval Cancer. The survival rate by the stage of the squamous cancer approaches 93% for stage 1; 79% for stage 2; 53% for stage 3 and 29% for stage 4
  • Vaginal Cancer: The survival rate by the stage of the squamous cancer approaches 84% for stage 1; 75% for stage 2; 57% for stage 3&4.

 

The above graph demonstrates the importance of screening for uterine corpus cancer and ovarian cancer in the peri-menopausal and postmenopausal age groups. The tools available are imperfect however :

  1. Uterine corpus cancers can be predicted using ultrasonic endometrial thickness >5 mm in the postmenopausal age group (especially in menopausal diabetics and Tamoxifen treated patients who are at greater risk)
  2. Ovarian tumour markers have been improved using a risk of ovarian malignancy algorithm (ROMA) based on the levels of CA125 and HE4. Furthermore BRCA gene testing may stratify risk in those with a family history.

Savings Expected by New Cervical Screening Program (CSP)

After implementation of the National Cervical Screening Program in 1991, incidence of cervical cancer declined by 36%, and mortality by 44%, by the mid-2000s. In Australia, the emergent evidence on HPV screening in conjunction with the introduction of HPV vaccination, and the comparatively longer screening intervals and narrower age range for screening recommended by the International Agency for Research on Cancer prompted a major review of the National Cervical Screening Program. The annual cost of the National Cervical Screening Program was estimated to be AUS$215 million in 2015. The estimated saving of the new program using HPV screening is 26%. What is uncertain is the national cost of delays in the diagnosis of non-cervical gynaecological cancers as a result of the reduced incentive to visit the doctor more frequently than every 5 years because of the new CSP. 

Further reading:

1.Ferley J, Shin HR, Bray F, et al. GLOBOCAN 2008 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 International Agency for Research on Cancer; [October 5, 2011]. 2010. Available from: http://globocan.iarc.fr.

2. Lew J-B et al Primary HPV testing versus cytology-based cervical screening in women in Australia vaccinated for HPV and unvaccinated: effectiveness and economic assessment for the National Cervical Screening Program The Lancet 2017 2(2):e96-e107

Posted in: Other  

Inaugural South Pacific Medical Student's Medical Camp

Posted by Professor Mike O’Connor AM on 1 January 2018

I recently returned from the inaugural South Pacific Medical Student's Medical Camp in Malolo Island, Fiji.

120 medical students from Fiji, Tonga, Samoa, Papua New Guinea as well as New Zealand and Australia spent a week on a tribal area in the school grounds courtesy of the local chief. The dais was a single structure decorated with palm leaves and the audience sat under a similar structure 25 metres away. There were some fascinating lectures from plant biologists, climatologists, epidemiologists and radiation oncologists. Fiji is soon to get its first radiation oncology centre. I spoke on maternal sepsis and gave tutorials on introductory O&G ultrasound using a portable Vinno ultrasound and a phantom female pelvis .The latter caused some raised eyebrows in Fijian Customs at Nadi Airport. The open boat trip to Malolo in rough seas was particularly interesting as I feared the ultrasound equipment might vanish over the side but that was not to be.

It was very apparent that these young medical students have grave concerns about global warming, rising sea levels and the spread of tropical disease.They may well be on the right track.

Posted in: Other  

Ovarian Tumour Markers-false positives

Posted by Professor Mike O’Connor AM on 21 November 2016

The use of ovarian tumour mark-ers, like those for other tumours, are used both to suggest the presence of a tumour as well as monitor its remission after de-finitive treatment. The problem is the lack of specificity which means that many non malignant processes can be associated with elevated values or that the malignancy is non-gynaecological.

CA125. Cancer antigen 125 (CA 125) is used the most extensively. Approximately 60% of malignant ovarian tumours are associated with an elevated CA125-often the level being >200 U/ml. Other diagnos-tic tests for epithelial ovarian cancer in-clude human epididymis protein (HE4), the OVA1 panel, and the Risk of Malig-nancy Algorithm (ROMA).

The CA 125 antigen is a large transmembrane glycoprotein derived from both coelomic (pericardium, pleura, peri-toneum) and müllerian (fallopian tubal, endometrial, endocervical) epithelia .The antigen is not specific to ovarian cancer as raised serum levels may also be found in 29% of other cancers (lung, breast, pan-creas, and colo-rectum) and in 6% of women with non-malignant conditions such as cirrhosis with ascites, acute pan-creatitis, ovarian cysts, endometriosis, and pelvic inflammatory disease. A Norwegian study showed that approximately 25% of blood samples had raised serum CA125 levels within 60 months preceding the di-agnosis of ovarian cancer .CA125 can be used to monitor the efficacy of treatment for ovarian cancer.

CA19.9
Cancer antigen 19-9 (CA 19-9) is a mucin protein that may be elevated in ovarian cancer or mucinous benign ovarian tu-mours. It may be elevated in endometrio-sis.

CA 19-9 is used primarily to monitor dis-ease response to therapy or detect cancer recurrence in patients with a documented gastric cancer, pancreatic cancer, gallbladder cancer, cholangiocarcinoma, or adenocarcinoma of the ampulla of Va-ter.

Endometriosis & CA125
Plasma concentrations of CA125 are markedly elevated in women with cystic ovarian endometriosis and/or deeply infil-trating endometriosis, but not, or only slightly, in the luteal phase of women with minimal or mild endometriosis .Overall the incidence of a raised CA125 is ap-proximately 30%.Serum CA125 is not a good marker for endometriosis but it is a helpful additional parameter to diagnose endometriotic disease in patients with chronic pelvic pain. Following treatment of endometriosis, elevated plasma concen-trations of CA125 can be used to signal that treatment has been incomplete, or that the condition has recurred .In clini-cal practice, 93% of women with a serum CA-125 level of 30 U/mL or higher who have had the diagnoses of adenomyosis, leiomyomas, ovarian tumors, pelvic in-flammation, and/or pregnancy ruled out will be shown to have endometriosis on further diagnostic testing .

 

Ovarian Cancer may originate in the Fallopian Tube

HE4 The human epididymis protein 4 (HE4) is elevated in patients with serous or endometrioid ovarian carcinoma. It is also used for the evaluation of an adnexal mass as a component of the Risk of Malignancy Algorithm (ROMA). False positives occur
with impaired renal function.

High-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian cancer. Research over the past decade has strongly suggested that "ovarian" HGSC arises in the epithelium of the distal fallopian tube, with serous tubal intraepithelial
carcinomas (STICs) being detected in 5-10% of BRCA1/2 mutation carriers undergoing risk-reducing surgery and up to 60% of unselected women with pelvic HGSC

About 75-80% of women with advanced ovarian cancer will have an elevated CA125 but only 50% of early ovarian cancers have a raised CA125.

 

 

Posted in: Ovaries  
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