Raised CA 125

This blog post covers important points about CA125 which are taken from a recently published TOG article in January 2021. CA125 has been used as a tumor marker for ovarian cancer but with some limitations. 

I hope this quick post is helpful. 

Feel free to leave your feedback in comments and suggestions to improve future posts are welcome.

Thanks

Introduction

• Leading cause of death from any gynae malignancy → Ovarian Cancer
• Over 70% present with late stage disease (Stage III or IV)
• Normal Level CA 125→ <35 IU/ml
• Level can increase in both physiological or pathological conditions
• CA125 expressed in tissues derived from embryonic coelomic epithelia which includes endometrium, mullerian epithelium, peritoneum, pleura & pericardium
• CA125 has role in cell-mediated immunity
• Antigen is not produced directly by tumour & not a tumour marker per se

CA125 & mechanical stress

• Highest levels of CA125 seen in ascites associated with ovarian cancer
• CA125 correlates positively with ascites volume
• Levels are much higher in ascitic fluid than blood levels which shows that antigen originates in ascitic fluid rather than tumour itself

Ovarian Cancer & CA125

Use in Diagnosis

• CA125 increased in epithelial ovarian cancers & less commonly in non-epithelial
• Used with TVS to calculate RMI which guides further management
• If RMI >250 iu/ml → Refer to Cancer Centre
• 50% with stage I & occult cancers have normal levels

Use in follow-up

• After surgical resection→ serum levels fall by half within 10 days

GTG 69 NVP & Hyperemesis Gravidarum

This is the summary of GTG -69 Hyperemesis Gravidarum released in 2016. This is one of a frequently tested guideline in the exam. Nausea and vomiting of pregnancy is one the most common indication for admission with typical stay of 3-4 days in the Hopsital. Hyperemesis Gravidarum is the severe form of NVP which can adversely affect the QoL and has a high recurrence in next pregnancy. 

I hope this post is helpful. Suggestions to improve future posts are welcome.

Thanks

To download the full GTG 69 Click Here

All GTGs links Click Here

Epidemiology

NVP symptoms of nausea ± vomiting during early pregnancy where no other causes 80%

HG severe form of NVP 0.3-3.6%

Recurrence 15%-80% 

• Reduced if change in paternity in second pregnancy 10.9%

Diagnosis of NVP & HG

NVP diagnosis  ONLY when onset in 1st trimester + other causes excluded 

• If after 10+6 wk→ consider other causes 
• Typically starts 4-7th wk Peaks 9th wk Resolves by 20 wk in 90%

HG diagnosis Protracted NVP with triad of >5% pre-pregnancy weight loss, dehydration & electrolyte imbalance

Severity NVP classify Objective & validated index of N & V PUQE Pregnancy Unique Quantification of Emesis

Initial clinical assessment & baseline investigations

• Features in history, examination & investigations to asses & diagnose NVP and HG for monitoring of the severity

Myocardial Infarction in Pregnancy

This blog post is based on an old yet very important TOG “Myocardial Infarction and Pregnancy” published in 2013. As cardiac disease is the leading cause of maternal death in UK, so this article is a must to cover before the exam. 

I hope this summary is helpful.

To download the original article: Click Here

To access all TOG articles: Click Here

Outline of Maternal Medicine Module: Click Here

To access other TOG summaries: Click Here

Introduction

• Heart disease 
• complicates → 0.2-4% of all pregnancies
• In UK the leading cause of maternal death since 2000
• 1/5th of All maternal deaths
• Majority due to acquired heart disease
• Acute Myocardial Infarction (AMI) → rare but in pregnancy RR is 3-4x higher
• Be aware of pregnancy specific physiological changes in CVS & keep low threshold for dx & mx

Physiological changes in pregnancy

Cardiovascular changes

• ↑ plasma volume & ↓ peripheral resistance as early as 6 wks
• ↑ in blood volume until plateaus at 140-150% @32 wks
• ↑ Cardiac output until 25wk first d/t ↑ in stroke volume & then d/t ↑ in maternal HR
• Further haemodynamic changes during labour & delivery

• Cardiac output→ ↑ by 50% with each contraction
• 300-400ml blood transferred from uterus with each contraction
• Valselva manoeuvre→ large variations in CVP
• After 3rd stage completed→ approx.500 ml uterine blood returns to circulation→ ↑ ventricular preload, cardiac output & CVP
• After 48 hrs→ diuresis & natriuresis starts. 
• Return of cardiac output , blood volume & peripheral resistance → pre-pregnancy state 4-12wks

Haematological changes

• Pregnancy a hypercoagulabale state 
• ↑ procoagulant: fibrinogen, factor VII, VIII & X & von Willebrand's factor

NICE: Diabetes in Pregnancy

This post is a summary of NICE guideline NG23 “Diabetes in Pregnancy” which was published in 2015. This guideline contains recommendations for managing diabetes & its complications in women who are planning pregnancy /already pregnant.

This is one of ‘the must’ guideline for the MRCOG exams. I have extracted only the main points. It is recommended to read the full guideline to ensure that no important points are missed.

I hope this is helpful. Your feedback and suggestions to improve further posts are welcome.

Thanks

To download full guideline Click Here

To download all NICE guidelines Click Here

INTRODUCTION

• 5% pregnancies are complicated by diabetes
• 87.5% → gestational diabetes
• 7.5% → type1
• 5% → type 2
• Risks to woman & fetus
• Miscarriage, pre-eclampsia & preterm labour are more common with pre-existing diabetes
• Diabetic retinopathy can worsen rapidly during pregnancy
• Stillbirth, congenital malformations, macrosomia, birth injury, perinatal mortality & postnatal adaptation problems are more common in babies born to women with pre-existing diabetes

PRECONCEPTION PLANNING AND CARE

• Good blood glucose control before conception & continuing it throughout pregnancy reduces the risk of miscarriage, congenital malformation, stillbirth & neonatal death
• Risks can be reduced but not eliminated
• Important to avoid unplanned pregnancies & effective contraception
• Provide information about how diabetes affects pregnancy and how pregnancy affects diabetes
• Make sure woman enters pregnancy in best optimum health in order to avoid complications
• BMI ≥27 offer advice on weight loss
• Prescribe folic acid 5 mg/day to reduce risk of baby with neural tube defects

Monitoring of blood glucose & ketones in the preconception period

• Offer monthly HbA1c to those diabetics planning to become pregnant
• Teach self-monitoring of blood sugar levels& use of glucometer

Target blood glucose and HbA1c levels

• Aim for same capillary plasma glucose target ranges as recommended for all people with type 1 diabetes
• Aim to keep HbA1c levels below 48 mmol/mol (6.5%)
• Advise against pregnancy if HbA1c level above 86 mmol/mol (10%)

Safety of medicine for diabetes before and during pregnancy

• Metformin can be used
• All other oral blood glucose-lowering agents should be discontinued before pregnancy & insulin substituted

GTG# 38 Management of Gestational Trophoblastic Disease

This post is the summary of green-top guideline GTG 38 “Management of Gestational Trophoblastic Disease” which was published in September 2020.  The new version of the guideline has some changes, so it is important to cover it. There are some important numbers which are tested repeatedly in exams. It is strongly encouraged to go through the original guideline to make sure that no point is missed. 

I hope this post is helpful. Suggestions to improve future posts are welcome.

To Download the Guideline 38: Click Here

All GreenTop Guidelines: Click Here

Definitions

Gestational trophoblastic disease (GTD) is a group of disorders ranging from premalignant (complete & partial mole also called hydatidiform mole) to malignant (invasive mole, choriocarcinoma, placental site specific trophoblastic tumour (PSTT) and epithelium trophoblastic tumour (ETT)

Gestational trophoblastic neoplasia (GTN): persistence of GTD after primary treatment (persistent elevation of HCG)

Histological confirmation for diagnosis

• Required for complete/partial mole
• Not required for GTN

Introduction & Background

Molar pregnancy subdivided into complete and partial mole 

Complete Mole	Partial Mole
Diploid & androgenic in origin	Triploid 90% Tetraploid or mosaic occasionally
No fetal tissue	Fetus or fetal RBCs present
75-80% arise due to duplication of single sperm after fertilisation of an ‘empty’ ovum	2 sets of paternal haploid & 1 set of maternal haploid chromosomes
20-25% due to dispermic fertilization of an ‘empty ovum’	Not all triploid or tetraploid pregnancies are partial moles Must have histopathological evidence of trophoblast hyperplasia for dx

GTD (Hydatidiform mole, Invasive mole, Choriocarcinoma, PSTT)

• Uncommon in UK
• Incidence 1 in 714 live births
• Ethnic variation Asian 1 in 387 live births Non-Asian 1 in 752 live births
• Associated with age at conception, higher in extremes of age
• <15 yrs 1 in 500 pregnancies >50 yrs 1 in 8 pregnancies 

GTN 

• May develop after molar/non-molar pregnancy or a live birth
• 1 in 50 000 after live birth 
• On average, a consultant O &G will deal with one new case every 2 years

Registration & Treatment Program UK

• Effective with cure rates of 98-100% 
• Chemotherapy Needed in 
• 0.5-1.0% after partial mole 
• 13-16% after complete mole
• Registration with GTD is a minimum standard of care

Presentation of Molar Pregnancy

• Most common presentation is irregular vaginal bleeding (60%), positive pregnancy test & supporting USG evidence (12%)
• Less common hyperemesis, excessive uterine enlargement, hyperthyroidism, early-onset pre-eclampsia (PET) & abdominal dissension due to theca lutein cysts
• Very rarely: haemoptysis or seizures— metastasis in lungs or brain

Role of USG

• USG use has lead to earlier diagnosis of molar. Reduction in mean gestation age of diagnosis from 16 to 9 weeks (over 1988- 2013)
• Majority of histologically proven molar → associated with USG diagnosis of delayed miscarriage or an-embryonic pregnancy
• Pre-removal accuracy of diagnosis increases with gestational age 
• 35-40% before 14wks
• 60% after 14 wks 
• USG correctly identified 56% of molar pregnancies with suspected missed miscarriage
• Unrecognised GTD prior to removal → 2.7%