Tumour Markers: An Overview

Tumour markers are substances produced by cancer cells or normal cells in response to cancer. They can be used to aid in the diagnosis, monitoring, and treatment of cancer. Here are some commonly used tumour markers and their applications:

CA125: This marker is used to detect ovarian cancer. It should be tested if a woman has persistent abdominal bloating, early satiety, pelvic or abdominal pain, increased urinary urgency or frequency, or symptoms consistent with irritable bowel syndrome. If CA125 is raised, the patient should be referred for a pelvic/abdominal ultrasound scan.

AFP: Elevated AFP levels are associated with hepatocellular carcinoma, liver metastases, and non-seminomatous germ-cell tumours. It is also measured in pregnant women to screen for neural-tube defects or genetic disorders.

CA15-3: This marker is used to monitor the response to treatment in breast cancer. It should not be used for screening as it is not necessarily raised in early breast cancer. Other causes of raised CA15-3 include liver cirrhosis, hepatitis, autoimmune conditions, and benign disorders of the ovary or breast.

CA19-9: This marker is commonly associated with pancreatic cancer. It may also be seen in other hepatobiliary and gastric malignancies.

CEA: CEA is commonly used as a tumour marker for colorectal cancer. It is not particularly sensitive or specific, so it is usually used to monitor response to treatment or detect disease recurrence.

Total Anomalous Pulmonary Venous Connection

Total anomalous pulmonary venous connection (TAPVC) is a condition that causes cyanosis in newborns. It is characterized by an abnormality in blood flow where all four pulmonary veins drain into systemic veins or the right atrium, with or without pulmonary venous obstruction. This results in the mixing of systemic and pulmonary venous blood in the right atrium.

In contrast, conditions such as patent ductus arteriosus (PDA), atrial septal defect (ASD), and ventricular septal defect (VSD) are left to right shunts. Tricuspid atresia is another condition that is typically associated with cyanosis, but mitral regurgitation is not.

It is important to understand the differences between these conditions and their effects on blood flow in order to properly diagnose and treat them. Further reading on TAPVC can be found on Medscape.

Antidotes for Common Drug Overdoses

In cases of drug overdose, specific antidotes can be administered to counteract the toxic effects of the drug. Here are some examples:

Ethylene glycol and fomepizole: Fomepizole is the preferred treatment for ethylene glycol and methanol poisoning. Ethylene glycol is broken down by alcohol dehydrogenase, but if this enzyme is overwhelmed, toxic metabolites can form. Fomepizole blocks alcohol dehydrogenase, preventing the formation of toxic metabolites.

Paracetamol and bicarbonate: N-Acetylcysteine is used to treat paracetamol overdose, while sodium bicarbonate is used for tricyclic antidepressant overdose.

Benzodiazepines and naloxone: Naloxone is the antidote for opiate overdose, while flumazenil can reverse the effects of benzodiazepines.

Digoxin and calcium: Digoxin antibodies (Digibind®) can be used in severe cases of digoxin overdose.

Beta-blockers and adrenaline: Glucagon and cardiac pacing are used to treat beta-blocker overdose.

Knowing the appropriate antidote for a specific drug overdose can be life-saving. It is important to seek medical attention immediately in cases of suspected overdose.

Adults with polycystic kidney disease are at an increased risk of experiencing subarachnoid haemorrhage due to ruptured berry aneurysms. This is the most significant associated condition, as ADPKD is known to be linked with cerebral berry aneurysms that can rupture and cause subarachnoid haemorrhage. Liver cysts are the most common complication of ADPKD, while colonic diverticula and bowel obstruction are less frequent. Although ADPKD can cause splenic cysts and splenomegaly, this is also less common than the risk of subarachnoid haemorrhage due to cerebral berry aneurysms.

Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent genetic condition that affects approximately 1 in 1,000 Caucasians. The disease is caused by mutations in two genes, PKD1 and PKD2, which produce polycystin-1 and polycystin-2, respectively. ADPKD type 1 accounts for 85% of cases, while ADPKD type 2 accounts for the remaining 15%. Individuals with ADPKD develop multiple fluid-filled cysts in their kidneys, which can lead to renal failure.

To diagnose ADPKD in individuals with a positive family history, an abdominal ultrasound is typically performed. The diagnostic criteria for ultrasound include the presence of two cysts, either unilateral or bilateral, in individuals under 30 years of age, two cysts in both kidneys for those aged 30-59 years, and four cysts in both kidneys for those over 60 years of age.

Management of ADPKD may involve the use of tolvaptan, a vasopressin receptor 2 antagonist, for select patients. Tolvaptan has been recommended by NICE as an option for treating ADPKD in adults with chronic kidney disease stage 2 or 3 at the start of treatment, evidence of rapidly progressing disease, and if the company provides it with the agreed discount in the patient access scheme. The goal of treatment is to slow the progression of cyst development and renal insufficiency. An enlarged kidney with extensive cysts is a common finding in individuals with ADPKD.

This woman’s ASA II classification is attributed to her history of smoking, well-managed diabetes and blood pressure. It is probable that her elevated BMI is a result of her consumption of high-fat foods, although this requires verification.

The American Society of Anaesthesiologists (ASA) classification is a system used to categorize patients based on their overall health status and the potential risks associated with administering anesthesia. There are six different classifications, ranging from ASA I (a normal healthy patient) to ASA VI (a declared brain-dead patient whose organs are being removed for donor purposes).

ASA II patients have mild systemic disease, but without any significant functional limitations. Examples of mild diseases include current smoking, social alcohol drinking, pregnancy, obesity, and well-controlled diabetes mellitus or hypertension. ASA III patients have severe systemic disease and substantive functional limitations, with one or more moderate to severe diseases. Examples include poorly controlled diabetes mellitus or hypertension, COPD, morbid obesity, active hepatitis, alcohol dependence or abuse, implanted pacemaker, moderate reduction of ejection fraction, End-Stage Renal Disease (ESRD) undergoing regularly scheduled dialysis, history of myocardial infarction, and cerebrovascular accidents.

ASA IV patients have severe systemic disease that poses a constant threat to life, such as recent myocardial infarction or cerebrovascular accidents, ongoing cardiac ischemia or severe valve dysfunction, severe reduction of ejection fraction, sepsis, DIC, ARD, or ESRD not undergoing regularly scheduled dialysis. ASA V patients are moribund and not expected to survive without the operation, such as ruptured abdominal or thoracic aneurysm, massive trauma, intracranial bleed with mass effect, ischaemic bowel in the face of significant cardiac pathology, or multiple organ/system dysfunction. Finally, ASA VI patients are declared brain-dead and their organs are being removed for donor purposes.

If pelvic floor muscle exercises and surgical intervention are not effective, duloxetine can be used to treat stress incontinence in patients. However, it is important to rule out other potential causes such as infection before starting treatment. Non-pharmacological management should be attempted first, including pelvic floor exercises and reducing caffeine intake. Duloxetine is a medication that works as a serotonin/norepinephrine reuptake inhibitor and may cause side effects such as nausea, dizziness, and insomnia. For urge incontinence, antimuscarinic agents like oxybutynin, tolterodine, and solifenacin are typically used as first-line treatment. If these are not effective, a β3 agonist called mirabegron can be used as a second-line therapy.

Understanding Urinary Incontinence: Causes, Classification, and Management

Urinary incontinence (UI) is a common condition that affects around 4-5% of the population, with elderly females being more susceptible. Several risk factors contribute to UI, including advancing age, previous pregnancy and childbirth, high body mass index, hysterectomy, and family history. UI can be classified into different types, such as overactive bladder (OAB)/urge incontinence, stress incontinence, mixed incontinence, overflow incontinence, and functional incontinence.

Initial investigation of UI involves completing bladder diaries for at least three days, vaginal examination, urine dipstick and culture, and urodynamic studies. Management of UI depends on the predominant type of incontinence. For urge incontinence, bladder retraining and bladder stabilizing drugs such as antimuscarinics are recommended. For stress incontinence, pelvic floor muscle training and surgical procedures such as retropubic mid-urethral tape procedures may be offered. Duloxetine, a combined noradrenaline and serotonin reuptake inhibitor, may also be used as an alternative to surgery.

In summary, understanding the causes, classification, and management of UI is crucial in providing appropriate care for patients. Early diagnosis and intervention can significantly improve the quality of life for those affected by this condition.

Common Genetic Disorders and Their Prenatal Ultrasound Findings

Prenatal ultrasound is a valuable tool for detecting genetic disorders in fetuses. Here are some common genetic disorders and their corresponding ultrasound findings:

1. Patau Syndrome (Trisomy 13)
Trisomy 13 has a prevalence of 1 per 6500 births. Fetuses with trisomy 13 may have brain anomalies such as holoprosencephaly, midfacial hypoplasia, ventriculomegaly, and microcephaly. Other possible findings include cleft lip and palate, microphthalmia, hypotelorism, and cardiac defects.

2. Cystic Fibrosis (CF)
Hyperechogenic fetal bowel is a possible ultrasound finding in fetuses with CF. This may be a normal variant, but it can also be associated with severe disease.

3. Down Syndrome
20% of second-trimester fetuses with Down syndrome have major structural anomalies such as polyhydramnios, double bubble, and large cardiac septal defects. Other possible markers include nuchal fold thickness, pyelectasis, and short long bones.

4. Klinefelter Syndrome
Klinefelter syndrome is characterized by two or more X chromosomes in boys, resulting in infertility and small testicles. Ultrasound findings may be subtle, and many people may not realize they are affected.

5. Potter Syndrome
Potter syndrome is suspected when severe oligohydramnios and intrauterine growth retardation are present. Ultrasound findings may include pulmonary hypoplasia, abnormal facies, and limb abnormalities such as club feet and contractures.

In conclusion, prenatal ultrasound can provide valuable information for detecting genetic disorders in fetuses. It is important for healthcare providers to be aware of the possible ultrasound findings associated with these disorders.

Investigation is necessary for any postmenopausal bleeding. The first step is to conduct a transvaginal ultrasound scan to examine the thickness of the endometrium. To diagnose endometrial cancer, a Pipelle biopsy is used to sample the endometrium, which is effective in most cases. Hysteroscopy with directed sampling (dilation and curettage) can be used to detect lesions or when Pipelle has been inconclusive. CT scan is not required as a pre-operative imaging test nor is it used to diagnose endometrial cancer.
Reference: Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, et al. Endometrial cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 (6): vi33-vi38.

Endometrial cancer is a type of cancer that is commonly found in women who have gone through menopause, but it can also occur in around 25% of cases before menopause. The prognosis for this type of cancer is usually good due to early detection. There are several risk factors associated with endometrial cancer, including obesity, nulliparity, early menarche, late menopause, unopposed estrogen, diabetes mellitus, tamoxifen, polycystic ovarian syndrome, and hereditary non-polyposis colorectal carcinoma. Postmenopausal bleeding is the most common symptom of endometrial cancer, which is usually slight and intermittent initially before becoming more heavy. Pain is not common and typically signifies extensive disease, while vaginal discharge is unusual.

When investigating endometrial cancer, women who are 55 years or older and present with postmenopausal bleeding should be referred using the suspected cancer pathway. The first-line investigation is trans-vaginal ultrasound, which has a high negative predictive value for a normal endometrial thickness (< 4 mm). Hysteroscopy with endometrial biopsy is also commonly used for investigation. The management of localized disease involves total abdominal hysterectomy with bilateral salpingo-oophorectomy, while patients with high-risk disease may have postoperative radiotherapy. progesterone therapy is sometimes used in frail elderly women who are not considered suitable for surgery. It is important to note that the combined oral contraceptive pill and smoking are protective against endometrial cancer.

If the foetus is in a breech position at 36 weeks, it is recommended to undergo external cephalic version. However, before 36 weeks, the foetus may naturally move into the correct position, making the procedure unnecessary. It is not necessary to schedule a Caesarean section immediately, but if ECV is unsuccessful, a decision must be made regarding the risks of a vaginal delivery with a breech presentation or a Caesarean section.

Breech presentation occurs when the caudal end of the fetus is in the lower segment, and it is more common at 28 weeks than near term. Risk factors include uterine malformations, placenta praevia, and fetal abnormalities. Management options include spontaneous turning, external cephalic version (ECV), planned caesarean section, or vaginal delivery. The RCOG recommends informing women that planned caesarean section reduces perinatal mortality and early neonatal morbidity, but there is no evidence that the long-term health of babies is influenced by how they are born. ECV is contraindicated in certain cases, such as where caesarean delivery is required or there is an abnormal cardiotocography.

Mycoplasma pneumonia commonly affects individuals aged 15-30 years and presents with systemic upset, dry cough, fever, myalgia, and arthralgia. It can also cause extrapulmonary manifestations such as haemolytic anaemia, renal failure, hepatitis, myocarditis, meningism, transverse myelitis, cerebellar ataxia, and erythema multiforme. Haemolysis is associated with the presence of cold agglutinins. Diagnosis is based on the demonstration of anti-mycoplasma antibodies in paired sera.

The Levonorgestrel intrauterine system is the appropriate choice for this patient as it is a long-acting contraceptive that can also help prevent heavy menstrual bleeding. It can be inserted immediately as the patient is within 48 hours of childbirth. The Copper intrauterine device should be avoided in those with a history of heavy menstrual bleeding. The lactational amenorrhoea method is only effective for up to 6 months post-partum, and progesterone injections must be repeated every 10-12 weeks, making them unsuitable for this patient’s desire for a long-term contraceptive.

After giving birth, women need to use contraception after 21 days. The progesterone-only pill (POP) can be started at any time postpartum, according to the FSRH. Additional contraception should be used for the first two days after day 21. A small amount of progesterone enters breast milk, but it is not harmful to the infant. On the other hand, the combined oral contraceptive pill (COCP) is absolutely contraindicated (UKMEC 4) if breastfeeding is less than six weeks post-partum. If breastfeeding is between six weeks and six months postpartum, it is a UKMEC 2. The COCP may reduce breast milk production in lactating mothers. It should not be used in the first 21 days due to the increased venous thromboembolism risk post-partum. After day 21, additional contraception should be used for the first seven days. The intrauterine device or intrauterine system can be inserted within 48 hours of childbirth or after four weeks.

The lactational amenorrhoea method (LAM) is 98% effective if the woman is fully breastfeeding (no supplementary feeds), amenorrhoeic, and less than six months post-partum. It is important to note that an inter-pregnancy interval of less than 12 months between childbirth and conceiving again is associated with an increased risk of preterm birth, low birth weight, and small for gestational age babies.

Common Congenital Heart Abnormalities in Down Syndrome Patients

Down syndrome is a genetic disorder that often presents with physical characteristics such as epicanthic folds, single creases, and an autosomal trisomy. It is estimated that 42% of children with Down syndrome have some form of congenital heart disease, with 23% having multiple abnormalities. The most common cardiac abnormality found in 37% of cases is a complete atrioventricular septal defect, followed by ventricular septal defects affecting 30% of patients. Other common heart abnormalities in Down syndrome patients include patent ductus arteriosus (2%), atrial septal defect (15%), and mitral valve disorders (up to 40%, but most commonly mitral valve prolapse or regurgitation rather than stenosis). It is important for healthcare providers to be aware of these potential heart abnormalities in Down syndrome patients for early detection and management.

This individual has reached the postmenopausal stage, indicated by the absence of menstruation for 12 consecutive months. However, despite being postmenopausal, she still requires contraception as she is below the age of 50. According to guidelines, women who use non-hormonal contraception can discontinue after one year of amenorrhea if they are over 50 years old, and after two years if they are under 50 years old. Given her history of breast cancer, a copper coil is the most suitable option as all other hormonal methods are classified as UKMEC Category 3, which may pose an unacceptable risk.

Women over 40 years old still need effective contraception until menopause. All methods of contraception are generally safe for this age group, except for the COCP and Depo-Provera which have some limitations. COCP use may help maintain bone mineral density and reduce menopausal symptoms, but a pill with less than 30 µg ethinylestradiol may be more suitable for women over 40. Depo-Provera use is associated with a small loss in bone mineral density and may cause a delay in the return of fertility for up to 1 year for women over 40. The FSRH provides guidance on how to stop different methods of contraception based on age and amenorrhea status. HRT cannot be relied upon for contraception, and a separate method is needed. The POP may be used with HRT as long as the HRT has a progesterone component, while the IUS is licensed to provide the progesterone component of HRT.

Hormonal Therapy for Biochemical Relapse in Prostate Cancer

According to NICE guidance, a biochemical relapse in prostate cancer, indicated by a rising PSA level, should not always lead to an immediate change in treatment. Hormonal therapy is not typically recommended for men with prostate cancer who experience a biochemical relapse unless they have symptomatic local disease progression, proven metastases, or a PSA doubling time of less than three months. In other words, if the cancer has not spread beyond the prostate and is not causing any symptoms, hormonal therapy may not be necessary. However, if the cancer has spread or is progressing rapidly, hormonal therapy may be recommended to slow down the cancer’s growth and improve the patient’s quality of life. It is important for patients to discuss their individual circumstances with their healthcare provider to determine the best course of action.

Common Side Effects of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve pain and inflammation. However, they can also cause side effects. The most common side effects of NSAIDs include facial flushing, which is caused by changes in prostaglandin metabolism. NSAIDs can also cause gastritis, peptic ulcer formation, hepatitis, gout, hyperglycemia, and rhabdomyolysis, especially when combined with statins. These side effects can be serious and should be monitored closely by a healthcare provider. It is important to discuss any concerns or questions about NSAIDs with a healthcare provider before taking them. Proper use and monitoring can help minimize the risk of side effects.

Diagnosing Acute Subdural Haematoma: Vital Clues and Differential Diagnoses

Acute subdural haematoma is a serious neurosurgical emergency that requires prompt diagnosis and intervention. Elderly patients and those on anticoagulant medications are at higher risk. A fluctuating conscious level in an elderly patient should raise suspicion. Vital clues from the patient’s history, such as a history of AF and fall, episode of urinary incontinence, and rapid drop in conscious level, should be considered. Urgent computed tomography (CT) brain imaging is necessary to exclude this diagnosis.

Other possible diagnoses, such as stroke, postictal state, obstructive sleep apnoea, and hypoglycaemia, may present with similar symptoms. However, given the history of a recent fall and deteriorating GCS, an intracranial event must be investigated. Checking the patient’s capillary glucose level is reasonable, but excluding an acute subdural haematoma is paramount.

For overweight or obese women with polycystic ovarian syndrome (PCOS) who are having difficulty getting pregnant, the initial approach is weight loss. If weight loss is not successful, either due to the woman’s inability to lose weight or failure to conceive despite weight loss, metformin can be used as an additional treatment.

Managing Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) is a condition that affects a significant percentage of women of reproductive age. The exact cause of PCOS is not fully understood, but it is associated with high levels of luteinizing hormone and hyperinsulinemia. Management of PCOS is complex and varies depending on the individual’s symptoms. Weight reduction is often recommended, and a combined oral contraceptive pill may be used to regulate menstrual cycles and manage hirsutism and acne. If these symptoms do not respond to the pill, topical eflornithine or medications like spironolactone, flutamide, and finasteride may be used under specialist supervision.

Infertility is another common issue associated with PCOS. Weight reduction is recommended, and the management of infertility should be supervised by a specialist. There is ongoing debate about the most effective treatment for infertility in patients with PCOS. Clomiphene is often used, but there is a potential risk of multiple pregnancies with anti-oestrogen therapies like Clomiphene. Metformin is also used, either alone or in combination with Clomiphene, particularly in patients who are obese. Gonadotrophins may also be used to stimulate ovulation. The Royal College of Obstetricians and Gynaecologists (RCOG) published an opinion paper in 2008 and concluded that on current evidence, metformin is not a first-line treatment of choice in the management of PCOS.

Drugs Associated with Gingival Hyperplasia

Gingival hyperplasia is a condition characterized by an overgrowth of gum tissue, which can lead to discomfort, difficulty in maintaining oral hygiene, and even tooth loss. There are several drugs that have been associated with this condition, including Phenytoin, Ciclosporin, and Nifedipine. These drugs are commonly used to treat various medical conditions, such as epilepsy, organ transplant rejection, and hypertension.

According to Medscape, drug-induced gingival hyperplasia is a well-known side effect of these medications. The exact mechanism by which these drugs cause gingival hyperplasia is not fully understood, but it is believed to be related to their effect on the immune system and the production of collagen in the gums.

It is important for healthcare providers to be aware of this potential side effect when prescribing these medications, and to monitor patients for any signs of gingival hyperplasia. Patients who are taking these drugs should also be advised to maintain good oral hygiene and to visit their dentist regularly for check-ups and cleanings.

In summary, Phenytoin, Ciclosporin, and Nifedipine are drugs that have been associated with gingival hyperplasia. Healthcare providers should be aware of this potential side effect and monitor patients accordingly, while patients should maintain good oral hygiene and visit their dentist regularly.

Finasteride: A 5-alpha-reductase Inhibitor

Finasteride is a medication that inhibits the enzyme 5-alpha-reductase, which is responsible for converting testosterone into dihydrotestosterone (DHT). By blocking this conversion, finasteride opposes the effects of testosterone, leading to common side effects such as gynaecomastia and reduced libido. However, it is also used orally as Propecia to treat male pattern hair loss.

Overall, finasteride is a potent medication that can have both positive and negative effects on the body. While it can help with hair loss, it is important to be aware of the potential side effects and to discuss any concerns with a healthcare provider.

Causes of Hyperkalaemia and Metabolic Acidosis with Normal Anion Gap

An Addisonian crisis is a severe form of adrenal insufficiency that can cause hyperkalaemia and metabolic acidosis with a normal anion gap. This condition may be due to previously undiagnosed Addison’s disease, sudden adrenal function impairment, or an intercurrent problem in someone with Addison’s. Excessive thiazide treatment, on the other hand, can result in hypokalaemia instead of hyperkalaemia.

Diabetic ketoacidosis is another condition that presents with hyperkalaemia and metabolic acidosis, but the anion gap is increased due to ketone bodies. Burns can also cause hyperkalaemia due to rhabdomyolysis, with an associated raised anion gap metabolic acidosis. Meanwhile, diarrhoea can cause hypokalaemia, hyponatraemia, loss of bicarbonate, and metabolic acidosis with a normal anion gap.