TURP syndrome

Cause and risk factors

• Water intoxication and acute dilutional hyponatremia
• Intravascular volume expansion causing circulatory overload
• Hypo-osmolality, leading to cerebral edema
• Irrigant-specific toxicity:
  • Glycine: visual disturbance, encephalopathy, seizures; metabolism may cause hyperammonemia
  • Sorbitol: hyperglycemia
  • Mannitol: volume expansion

• Long resection time, especially >1 hour
• Large prostate or extensive resection
• High irrigation-bag height and high intravesical pressure
• Large volume of irrigant used or absorbed
• Open venous sinuses and capsular perforation
• Reduced cardiac or renal reserve

Clinical presentation

• Nausea and vomiting
• Headache
• Restlessness, anxiety, agitation
• Blurred vision or transient visual loss, classically with glycine
• Confusion, reduced alertness

• Initially hypertension and bradycardia from volume expansion
• Dyspnea, hypoxemia/cyanosis
• Pulmonary edema and heart failure
• Arrhythmias
• Later, hypotension and shock may occur

• Marked confusion or obtundation
• Seizures
• Coma
• Death if untreated

Prevention

1. Prefer bipolar TURP with isotonic saline irrigation
   This avoids the hypo-osmolar hyponatremia associated with electrolyte-free hypotonic fluids. Saline absorption can still cause volume overload.
2. Limit duration and extent of resection
   Reassess carefully if irrigation/resection exceeds about 1 hour. Stage a large resection when needed.
3. Use the lowest effective irrigation pressure
   Keep intravesical pressure low, avoid excessive height of the irrigation bag, ensure unobstructed outflow, and avoid bladder overdistension.
4. Monitor irrigant fluid balance
   Measure fluid instilled versus recovered. A large unexplained fluid deficit suggests systemic absorption.
5. Stop or pause surgery if absorption is substantial
   Assess serum sodium and clinical state if there is concern for absorption. The textbook guidance advises stopping surgery at lower absorption thresholds, especially in women, and terminating for very high volumes.
   Miller's Anesthesia, 10e, p. 6373.
6. Use regional anesthesia where appropriate
   Spinal anesthesia may allow earlier recognition of nausea, visual symptoms, agitation, or confusion in an awake patient. Sedation should not mask these warning signs.
7. Monitor high-risk patients closely
   Monitor ECG, blood pressure, oxygenation, fluid balance, and check serum electrolytes when resection is prolonged or absorption is suspected.

Artificial Nutritional Support

1. Enteral nutrition (EN): nutrients delivered into the gastrointestinal tract through a tube.
2. Parenteral nutrition (PN): nutrients delivered intravenously, bypassing the gastrointestinal tract.

Indications

• Inadequate oral intake for a prolonged period or anticipated inability to eat
• Established malnutrition or high risk of malnutrition
• Hypermetabolic states, such as major trauma, burns, sepsis, or cancer
• Dysphagia due to stroke, neurological disease, or head and neck malignancy
• Critical illness requiring ventilatory support
• Major gastrointestinal surgery, especially when prolonged fasting is expected
• Malabsorption or increased nutrient losses

1. Enteral nutrition

Definition

Routes

• Nasogastric (NG) tube: nose to stomach
• Nasojejunal or nasoduodenal tube: nose to small bowel
• Orogastric tube: often in intubated patients

• Percutaneous endoscopic gastrostomy (PEG)
• Gastrostomy
• Jejunostomy

Indications

• Dysphagia after stroke
• Reduced consciousness with a protected airway
• Head and neck cancer
• Neurological disorders such as motor neuron disease
• Critically ill patients with a functioning gut
• Severe malnutrition with inadequate oral intake
• Postoperative patients in whom oral intake is delayed but bowel function is usable

Advantages

• More physiological and generally safer than PN
• Maintains gut mucosal integrity and intestinal motility
• Reduces bacterial translocation from the gut
• Usually causes fewer infective complications than PN
• Less expensive
• Can be used for prolonged nutritional support

Methods of administration

• Continuous feeding: pump-controlled, usually best tolerated in hospitalized or critically ill patients
• Intermittent feeding: feed given over 20 to 30 minutes at intervals
• Bolus feeding: larger volumes at intervals, suitable only for gastric feeding and stable patients

Contraindications to enteral feeding

• Intestinal obstruction
• Bowel perforation
• Intestinal ischemia
• Severe uncontrolled gastrointestinal bleeding
• Severe ileus
• High-output fistula where feeding distal to the fistula is not possible
• Intractable vomiting or severe diarrhea
• Severe hemodynamic instability or shock

Complications of enteral nutrition

• Tube malposition or displacement
• Nasal, pharyngeal, or esophageal injury
• Tube blockage
• Gastrostomy-site infection or leakage

• Regurgitation and aspiration pneumonia

• Nausea, vomiting, abdominal distension
• Diarrhea or constipation
• Cramps and bloating

• Hyperglycemia
• Electrolyte imbalance
• Fluid overload or dehydration
• Refeeding syndrome

2. Parenteral nutrition

Definition

• Supplementary PN: complements inadequate oral or enteral intake.
• Total parenteral nutrition (TPN): provides the entire nutritional requirement intravenously.

Indications

• Intestinal obstruction
• Paralytic ileus
• Short-bowel syndrome or extensive intestinal resection
• Severe malabsorption
• High-output enterocutaneous fistula
• Severe inflammatory bowel disease when enteral feeding cannot be tolerated
• Severe intestinal dysmotility
• Prolonged bowel rest required after certain surgical conditions

Routes of administration

• Peripheral parenteral nutrition (PPN): for short-term use and lower-osmolarity solutions. It has limited caloric capacity and may cause thrombophlebitis.
• Central parenteral nutrition: via a central venous catheter, PICC, tunneled catheter, or implanted port. This permits concentrated, high-osmolarity feeds and is used for longer duration or full nutritional requirements.

Composition of PN

• Water
• Glucose as carbohydrate
• Amino acids as protein source
• Lipid emulsion as calorie and essential-fatty-acid source
• Electrolytes: sodium, potassium, calcium, magnesium, phosphate
• Vitamins and trace elements
• Sometimes insulin, depending on glucose control

Complications of parenteral nutrition

• Pneumothorax, arterial puncture, air embolism during insertion
• Catheter occlusion or thrombosis
• Catheter-related bloodstream infection and sepsis

• Hyperglycemia or hypoglycemia
• Hypertriglyceridemia
• Electrolyte disturbances
• Fluid overload
• Acid-base disorders
• Refeeding syndrome

• Fatty liver and cholestasis
• Abnormal liver enzymes
• Gallbladder sludge or gallstones with long-term PN

Refeeding syndrome

• Cardiac arrhythmias and heart failure
• Muscle weakness
• Respiratory failure
• Confusion, seizures, or coma
• Fluid retention and edema

Prevention

• Identify high-risk patients before feeding
• Correct major electrolyte and fluid deficits
• Give thiamine before and during initial feeding
• Start feeding slowly and advance gradually
• Monitor phosphate, potassium, magnesium, glucose, fluid balance, and clinical status closely

Monitoring during artificial nutritional support

• Daily clinical examination and fluid balance
• Body weight and nutritional intake
• Blood glucose
• Serum electrolytes, especially phosphate, potassium, and magnesium
• Renal and liver function tests
• Full blood count when indicated
• Serum triglycerides in patients receiving intravenous lipids
• Enteral-feed tolerance: vomiting, distension, bowel movements, aspiration risk
• Catheter site and signs of infection in PN

Clinical interpretation

• cT3 cN0 cM0
• Anatomical stage IIB

a) Provisional and differential diagnosis

Provisional diagnosis

Differential diagnosis

1. Phyllodes tumour
   • Important differential in a young woman with a rapidly enlarging, large breast mass.
   • May be benign, borderline, or malignant.
   • Usually well-circumscribed and mobile, but large lesions may be firm and clinically mimic carcinoma.
2. Giant fibroadenoma
   • Common in young women.
   • Typically smooth, rubbery, highly mobile, and well defined rather than hard and infiltrative.
   • A rapidly growing lesion >3 cm requires tissue diagnosis to exclude phyllodes tumour.
3. Breast lymphoma or sarcoma
   • Uncommon but possible with a rapidly enlarging firm mass.
4. Pregnancy-associated breast cancer
   • Pregnancy test and menstrual history are important. A pregnancy-associated malignancy can present as a delayed or enlarging breast lump.
5. Mastitis or breast abscess
   • Less likely because the lump is hard and there is no stated pain, erythema, fever, or lactation.
6. Tuberculous mastitis or granulomatous mastitis
   • Consider in an endemic setting, particularly with sinus formation, axillary nodes, or inflammatory signs.

b) Etiopathogenesis of carcinoma breast

1. Molecular pathogenesis

• BRCA1 and BRCA2 mutations
  • Tumour-suppressor genes involved in DNA double-strand-break repair.
  • Germline mutations markedly increase risk, particularly in young women.
  • BRCA1-associated cancers are often high grade and triple negative.
• TP53 mutation
  • Common in high-grade and aggressive tumours.
• HER2/ERBB2 amplification
  • Causes overexpression of HER2 receptor tyrosine kinase.
  • Associated with an aggressive phenotype but predicts response to anti-HER2 therapy.
• PIK3CA pathway abnormalities
  • Common in hormone-receptor-positive breast cancer.
• Loss of CDH1 (E-cadherin)
  • Characteristic of invasive lobular carcinoma.

2. Hormonal and reproductive factors

• Early menarche
• Late menopause
• Nulliparity or low parity
• First full-term pregnancy after 30 years
• Lack of breastfeeding
• Exogenous hormones in selected circumstances
• Obesity, especially after menopause, due to peripheral estrogen formation

3. Genetic and familial risk factors

• First-degree relative with breast or ovarian cancer
• Young age of cancer onset in relatives
• Bilateral breast cancer
• Known familial pathogenic variants, especially BRCA1, BRCA2, PALB2, TP53, PTEN, and CHEK2

4. Other risk factors

• Previous chest irradiation, especially at a young age, such as for Hodgkin lymphoma
• Dense breasts
• Atypical ductal or lobular hyperplasia
• Lobular carcinoma in situ
• Alcohol use, obesity, inactivity, and smoking

c) Investigation and management

I. Investigations

1. Triple assessment

1. Clinical assessment
2. Imaging
3. Pathological tissue diagnosis

A. Clinical assessment

History

• Duration and rate of growth
• Pain, fever, nipple discharge, nipple retraction
• Skin changes, ulceration, or arm edema
• Menstrual and obstetric history
• Current pregnancy or lactation
• Oral contraceptive or hormone use
• Personal history of breast disease or irradiation
• Family history of breast, ovarian, pancreatic, prostate, or male breast cancer
• Constitutional symptoms and symptoms of metastasis:
  • Bone pain
  • Breathlessness/cough
  • Headache/seizures
  • Jaundice or abdominal pain
  • Weight loss

Examination

• Examine both breasts, including size, site, quadrant, surface, margins, mobility, fixation, and relation to skin and chest wall.
• Look for nipple distortion, discharge, peau d'orange, ulceration, satellite nodules, or inflammatory changes.
• Examine both axillae, supraclavicular and infraclavicular nodes.
• Examine liver, spine, chest, and neurological system for metastases.

B. Imaging

1. Bilateral diagnostic mammography
   • Include standard and additional views as needed.
   • Looks for mass, spiculation, microcalcifications, multifocality, and contralateral disease.
2. Breast and axillary ultrasound
   • Particularly important in this young woman with dense breasts.
   • Distinguishes cystic from solid lesions.
   • Evaluates the axilla and guides biopsy of suspicious axillary nodes.
3. Breast MRI with contrast Consider when:
   • Dense breasts or uncertainty regarding extent of disease
   • Suspected multifocal/multicentric disease
   • Discordance between clinical examination, imaging, and pathology
   • Assessment of response to neoadjuvant therapy
   • Possible hereditary breast cancer

C. Tissue diagnosis

• Histological type and grade
• Estrogen receptor (ER) status
• Progesterone receptor (PR) status
• HER2 status, with confirmatory testing when equivocal
• Ki-67 proliferation index where locally used

D. Staging and baseline tests

• CBC
• Renal function, liver function tests, serum calcium, alkaline phosphatase
• Pregnancy test before imaging, chemotherapy, endocrine treatment, or radiotherapy
• Chest imaging and abdominal imaging, commonly CT chest/abdomen/pelvis
• Bone scan or FDG PET-CT if symptoms, abnormal alkaline phosphatase, high-risk disease, or according to institutional staging protocol
• Baseline echocardiography or MUGA scan if anthracycline or HER2-targeted therapy is planned
• Fertility counselling and discussion of oocyte/embryo cryopreservation before chemotherapy

II. Management

• Histology and grade
• ER, PR, HER2 status
• Tumour size and location
• Nodal status
• Presence of distant metastasis
• Breast size and feasibility of breast conservation
• Patient preference, genetic risk, fertility plans, and general fitness

1. Neoadjuvant systemic therapy

• Shrinks tumour and may permit breast-conserving surgery
• Treats occult micrometastatic disease early
• Provides information on treatment response
• Helps tailor postoperative systemic treatment

Type of neoadjuvant treatment

2. Surgery

A. Breast-conserving surgery

• Tumour-to-breast size ratio is acceptable
• Adequate cosmetic result is feasible
• Disease is unifocal
• The patient can receive radiotherapy afterward

B. Mastectomy

• Tumour remains too large relative to breast size
• Multifocal or multicentric disease is present
• Clear margins cannot be achieved with conservation
• Radiotherapy is contraindicated
• The patient prefers mastectomy
• A high-risk genetic mutation makes risk-reducing contralateral surgery relevant after counselling

C. Axillary management

• Perform sentinel lymph-node biopsy (SLNB) at surgery if axillary imaging and biopsy are negative.
• If a node is proven positive before neoadjuvant therapy, management after treatment depends on response, clip retrieval, sentinel-node findings, and local protocols.
• Axillary lymph-node dissection is performed for significant residual nodal disease or when indicated by nodal burden.

3. Adjuvant treatment

Radiotherapy

• Mandatory after breast-conserving surgery.
• After mastectomy, indicated according to tumour size, margins, nodal status, response to neoadjuvant therapy, and other risk factors.
• A T3 tumour may require chest-wall radiotherapy even with negative nodes, depending on final pathology and multidisciplinary decision.

Endocrine therapy

• Premenopausal woman: tamoxifen, with or without ovarian function suppression depending on recurrence risk.
• Higher-risk patients may receive ovarian suppression plus an aromatase inhibitor under oncology supervision.

HER2-targeted therapy

Additional systemic therapy

• Tumour subtype
• Final pathological stage
• Nodal status
• Response to neoadjuvant treatment
• Presence of residual disease

Patient-specific plan

1. Refer urgently to a breast unit.
2. Perform triple assessment.
3. Obtain ultrasound-guided core biopsy of the mass.
4. Perform bilateral imaging and axillary ultrasound.
5. Test tumour for ER, PR, HER2, grade, and Ki-67.
6. Stage for distant metastases if malignancy is confirmed.
7. Offer genetic counselling/testing because of diagnosis at age 31.
8. Discuss fertility preservation before chemotherapy.
9. If invasive T3 carcinoma is confirmed, treat with subtype-guided neoadjuvant systemic therapy in most cases, followed by breast surgery with sentinel-node staging or indicated axillary surgery, radiotherapy, and subtype-specific adjuvant systemic treatment.