Investigation And Interpretation Notes

Investigation And Interpetion  Introduction

• When a surgical patient is investigated for a disease, many investigations are done. Often many of them may not help either in the diagnosis or in the treatment. Ultrasound examination is the most common non-invasive and simple preliminary investigation in abdominal conditions, breast, thyroid or any cystic swellings. It has been called extension of surgeon’s hand or extension of clinical examination.

Read And Learn More: Basic Principles Of Surgery Notes

• To avoid unnecessary investigations, proper history taking including co-existing diseases such as diabetes, hypertension, allergy, etc. followed by a thorough clinical examination must be done first. Once a working diagnosis is made, relevant investigations are ordered. One should then see the results, interpret and give appropriate treatment.
• As you read further lines, you will get a better understanding. This topic deals with only a few examples, but students are expected to apply these principles to every disease. I have given four examples to highlight the importance of the investigations.

Examples

Example 1. Carbuncle (multiple hair follicle infections) over the nape of the neck

This is a common problem in diabetic patients. Firstly, haematological investigations are ordered. Normal white cell count ranges between 4500 and 11000 cells per microliter. If white cell count is elevated, it indicates significant infection.

Important Points to Remember:

1. Investigations can be broadly classified as investigations that help in the diagnosis (to be done first), investigations that help in detecting spread of the disease (metastatic work-up in malignancies), and investigations to assess the fitness of the patient for surgery.
2. When you order investigations, ask yourself whether this investigation is necessary and will this patient benefit from this investigation?
3. Think twice before you order any invasive investigations that can be associated with serious complications. One example: Colonic perforation during colonoscopy. If you need to establish the diagnosis to prove tuberculosis/carcinoma, colonoscopy is certainly indicated. However, colonoscopy is not recommended for a patient with a 7-days history of constipation.
4. Need to know the side effects: Example: CECT scan. Exposure of the patient to CECT scan is equivalent to 200 chest X-rays and contrast used can give rise to renal failure.
5. Junior surgeons and postgraduates especially, who order investigations must also see the reports and try interpretation. If you have requested for MRI foot for diabetic foot, there is no need to obtain X-rays of the foot.
6. Two important biochemical investigations which are obtained in a diabetic patient are fasting blood sugar—FBS, and post-prandial blood sugar—PPBS and creatinine.
7. If blood sugars are high (FBS more than 150 mg/dl and PPBS more than 200 mg/dl), the patient has to be treated for diabetes. If serum creatinine is high, it indicates renal damage, and one has to be careful in selecting antibiotics—better to avoid gentamicin, amikacin, etc.
8. If doubtful of the diagnosis, ultrasound imaging can be requested to confirm the diagnosis. An abscess will appear hypoechoic.
9. Aspiration of pus seen at the ultrasound imaging is sent for culture and sensitivity.
10. It is usually caused by Staphylococcus aureus, and it responds to cloxacillin or clindamycin. If patient has toxicity, we may have to start vancomycin.
11. Once abscess is drained, the tissue is sent for microbiological examination again. The wall of the abscess cavity or tissue can also be sent to pathology depending upon the nature of the abscess. Then look at the histopathology report and plan further treatment, if necessary.
12. Thus, in this patient haematological investigations such as haemoglobin, total count including differential count of neutrophils, blood sugar and creatinine, imaging (may not be required in all), pus culture sensitivity are important.

Example 2. Toxic multinodular goitre:

• Haematological investigations are ordered. 4,500 to 11,000 WBCs per microliter (4.5 to 11.0 × 109/l) is normal white blood cells count or leucocyte count.
• If leucocyte counts are low (4,000 cells/µl), it indicates leukopenia. It may be side effect of drugs used to control toxicity. Example: Carbimazole, in this case.
• Thyroid hormone levels: T3 and T4 levels are elevated suggesting thyrotoxicosis. Usually, T4 toxicosis is common. When these hormones are elevated, thyroid-stimulating hormone (TSH) is very low due to feedback mechanism. In Hashimoto’s thyroiditis or in cases of hypothyroidism, TSH is elevated but T3 and T 4 are usually low. Hence, they need thyroid hormone supplementation.
• Ultrasound imaging is the first investigation. Look for nodules, nature of nodules, suggestion of malignancy (details are given in thyroid chapter).
• Ultrasound-guided FNAC is not done in toxic nodules but is routine in all thyroid swellings to rule out malignancy. If any mitotic figures or microcalcifications are present it will suggest malignancy.
• In large goitres, vital structrues such as trachea, esophagus, internal jugular vein and common carotid arteries are displaced or infiltrated as in malignant goitres. To identify these anatomical structures and to avoid injuries to these strictures, CECT scan can also be done.
• A few other investigations are done to assess fitness of the patient, to control comorbidity, if any, in this patient. Cardiac status—echocardiogram to know the ejection fraction, and if necessary, coronary angiogram in cases of myocardial ischemia.

Example 3. Obstructive jaundice:

As you can see here, sclera are stained with bilirubin—deep yellow coloured almost with greenish tinge due to biliverdin deposition. Following investigations are done and interpretations are given below. The patient had carcinoma head of the pancreas with palpable gallbladder.

1. Liver function test: Bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), albumin and total protein, gamma-glutamyl transferase (GGT), L-lactate dehydrogenase (LD), prothrombin time (PT).
2. Normal bilirubin levels are 0.2 to 0.6 mg/dl. Elevation beyond 2 mg/dl will be visible in the sclera. Very high values are often found in obstructive jaundice. If more than 50% of the total bilirubin is direct bilirubin, it is obstructive in origin. If more than 50% is indirect, it could be hemolytic jaundice.
3. ALT and AST levels are elevated in hepatitis because they represent hepatocellular damage.
4. ALP is elevated when there is obstruction to the biliary tree—classically in a patient with obstructive jaundice.
5. Albumin is synthesised only in the liver. Hence low levels of albumin is a feature of chronic liver disease or chronic malnutrition.
6. GGT: The main role of GGT is helping the liver in metabolising drugs or toxins. High levels of GGT are seen in liver diseases including chronic alcoholic liver damage and fatty liver.
7. LDH: Normal levels: 140 units per litre (U/L) to 280 U/L. Increased levels are seen in high tumour burden cases which means tumour is spreading. It can also be seen in benign conditions with increased tissue breakdown.
8. INR and prothrombin time will be prolonged.

• Culture and sensitivity: If patient has high grade fever with chills and rigors, it indicates cholangitis— send blood for culture and sensitivity. Invariably gramnegative organisms dominate along with other organisms.
• Imaging: When ultrasound probe is kept in the right hypochondrium, one can see dilated biliary radicles— which is the first indication of distal obstruction. If gallbladder is also enlarged, it will suggest lower bile duct obstruction.
• CT scan is done not only to confirm ultrasound findings but also to know the resectability by demonstrating plane between superior mesenteric vein/superior mesenteric artery—if it shows hypodense lesions, they suggest secondaries in the liver.
• Tumour markers such as CEA (carcinoembryonic antigen) and CA 19-9 were normal. Details about tumour markers are given in the respective topics such as gallbladder cancer, pancreatic head cancer and carcinoma colon, etc.
• One example of a typical patient with obstructive jaundice has been given here.
  • Total bilirubin (serum) (H) 20.94 mg/dl
  • Direct bilirubin (serum) (H) >17 mg/dl
  • Total protein (serum) 6.40 g/dl
  • Albumin (serum) 3.50 g/dl
  • Globulin 2.90 g/dl
  • Aspartate transaminase (AST) (serum) (H) 51 IU/L
  • Alanine transaminase (ALT) (serum) 32.0 IU/L
  • Alkaline phosphatase (ALP) (serum) (H) 568 U/L
• If you see this report of a jaundice patient, direct bilirubin is more than 50% of total bilirubin with very high values of alkaline phosphatase—it suggests obstructive jaundice.
• Tumour markers in this patient done were: CEA: 3.0 ng/ml and CA 19-9: 21 U/ml. These are done to find out or to get the clue about possibility of gallbladder cancer or carcinoma head of the pancreas.

Example 4. Carcinoma breast

• Initial triple assessment is done: Clinical examination, mammogram and tru-cut biopsy are done and carcinoma is confirmed.
• Then metastatic work-up: If chest X-ray shows cannon ball metastasis, it is a stage 4 disease.
• CT-PET scan is done to look for metastasis all over the body depending upon staging and grading of the tumours, etc. (details are given later).
• Core needle biopsy is subjected for immunohistochemistry. It is required to plan appropriate chemotherapy or hormonal therapy or therapy with newer agents including trastuzumab. Details of IHC are given below.

Immunohistochemistry (IHC)

Immunohistochemistry, also known as IHC, is an important diagnostic modality in the work-up of cancers. It is widely applied in the field of oncopathology to detect the presence of specific antigens on the tumour cell, that help in confirmation of cancers and their subtyping.

1. It is useful in identifying the cell type and origin of a metastasis to find the site of the primary tumour. IHC is also widely used to predict the response to therapy in various tumours, i.e. carcinoma of breast.
2. The technique involves fixing tumour tissue using a chemical such as formaldehyde which stabilises the structural properties of tissue.
3. The tissue is then incubated with an appropriate primary antibody against specific tumour antigens/proteins, followed by a secondary antibody that is conjugated with a dye or enzyme.
4. The binding of antigen on tumour with the antibody brings about a color reaction which is then visualized under microscope.
5. The panel of immunohistochemical antibodies available is substantial that are used as diagnostic, prognostic and predictive biomarkers. Following are some examples of commonly used IHC antibodies:

• Estrogen receptor (ER), progesterone receptor (PR), Her 2 and Ki 67 (proliferation marker) in breast cancers for subtyping and predicting response to therapy.
• Cytokeratin 7 and cytokeratin 20 in the work-up of metastasis of unknown origin.
• CD15 and CD30 in Hodgkin’s lymphoma (Fig. 9.5).
• CD19, 20 for B cell lymphomas, CD3 for T cell lymphoma.
• CD117 for gastrointestinal stromal tumours.
• CD99 and FLI 1 for Ewing’s sarcoma.
• Melanoma: S100
• Vascular: CD31, CD34
• Colorectum: Cytokeratin

• Ovary: CA125, CK20
• Prostate: PSA
• GIST: CD117
• Thus, immunohistochemical stains can detect all types of tumours and can confirm malignancy. S100 and actin stains can be used to identify the myoepithelial cell layer in a duct or gland.
• IHC may also help in selecting a treatment and making prognostic predictions. Examples: Carcinoma of the breast is assessed for oestrogen receptor, progesterone receptor, and HER2 status.
• IHC can also detect infections such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), etc. and detect an abnormal accumulation of proteins or amyloid.
• Please note: Abdominal investigations and interpretations require theoretical knowledge of both surgical and radiological investigations. One example of how to arrive at the diagnosis is given below. As you read the entire textbook you will be in a better position to understand this aspect.