Neutropenic enterocolitis
Major Criteria:
- Neutropaenia, < 500 x 109 cell/L
- Bowel wall thickening on CT exam or US exam
- Fever, > 38.3c oral or rectal
- > 4 mm (transverse scan) thickening in any segment of the bowel for at least 30 mm length (longitudinal scan)
Minor Criteria
- non-specific Abdominal pain > 5/10
- Abdominal distention
- Abdominal cramping
- Diarrhoea
- Lower GI bleeding
R-CHOP chemo Regimen
- Rituximab,
- Cyclophosphamide,
- Doxorubicin,
- Vincristine, and Prednisone
Anti-Neoplastic drugs and Skin Extravasation
- Irritant Antineoplastics:
- alkylating agents, platinum drugs, topoisomerase I inhibitors and 5-FU - Vessicant Antineoplastics:
tissue damage, blistering, gangrene
- Vinca alkaloids, anthracyclines, and taxanes - Non-vessicants are responsible for temporary erythema and oedema upon extravasation. Examples include cytarabine, gemcitabine and asparaginase.
Managing Chemo Extravasation
General treatment measures include discontinuation of the infusion, aspiration of fluid from the IV line, and elevation of the limb. Cold compressions are used for almost all drug extravasations; however, the management of vinca alkaloid extravasation is unique in requiring warm compressions to dissipate the drug from the affected site. Hyaluronidase helps reduce discomfort and latent cellulitis. Dexrazoxane and sodium thiosulfate are used for the extravasation of anthracyclines and cisplatin respectively.
Ultrasound features of Malignant Thyroid Nodule
Ultra-sound features suggestive of thyroid malignancy:
> 1cm sized nodule which is taller than it is wide
Microcalcification
Local invasion and lymph node metastases
Ill-defined and irregular margin and contour
Intrinsic hypervascularity
Solid and hypoechoic
Absence of a completely uniform halo around the nodule
Risk of Thyroid cancer
History of neck irradiation in childhood
Endemic goitre
Hashimoto’s thyroiditis (increased risk of lymphoma)
Family or personal history of thyroid adenoma
Cowden`s syndrome
Familial adenomatous polyposis
Familial thyroid cancer
Radio-iodine Recommendations
RAI is typically recommended if any of the following is present:
* Significant N1b disease
* Gross extrathyroidal extension
* Postoperative unstimulated Tg >10 ng/mL
* Bulky or >5 positive lymph nodes
* Vascular invasion
* Differentiated high-grade carcinoma
Actions to take if Thyroglobulin High/Rising (post total Thyroidectomy)
- Check Tg heterophile antibody levels to rule out interference in assay
- Check if the TSH is completely suppressed
- Did the patient undergo complete surgical resection
- Rule out any possible iodine contamination (e.g. amiodarone therapy or recent contrast injection) in cases where Tg is detectable and uptake scan negative
- Arrange a neck ultrasound to look for any thyroid remnant or lymph node enlargement
If neck ultrasound negative arrange for CT thorax - If both the above-mentioned investigations are negative arrange for a 99mTc MIBI to rule out bony deposits
- If all above-mentioned investigations are negative consider a PET scan, if that too is negative consider therapeutic 131I ablation
Acute Lymphoblastic Leukemia (ALL) Chemotherapy Regimens
Induction:
This initial phase aims to achieve remission (no detectable leukemia cells) and usually involves a short, intensive course of chemotherapy, including drugs like vincristine, daunorubicin (or doxorubicin), cyclophosphamide, pegaspargase, and corticosteroids.
Consolidation (Intensification):
This phase builds on the remission achieved in induction and includes more intensive chemotherapy, often with drugs like methotrexate and mercaptopurine.
Maintenance:
This phase helps to keep the leukemia in remission for a longer period and may involve lower doses of chemotherapy drugs like methotrexate and mercaptopurine, sometimes with vincristine and steroids.
Acute Myeloid Leukemia (AML) Chemotherapy Regimens
Remission Induction:
The most common approach is the “7+3” regimen, which combines cytarabine (given for 7 days) with an anthracycline drug like daunorubicin or idarubicin (given for 3 days).
Intensive Chemotherapy:
Other intensive chemotherapy regimens may include FLAG-Ida (fludarabine, cytarabine, idarubicin) or combinations with high-dose cytarabine.
Targeted Therapy:
Targeted therapies like midostaurin or quizartinib may be added if the leukemia cells have FLT3 mutations. Gemtuzumab ozogamicin (Mylotarg) is another targeted therapy drug used in AML.
Supportive care:
Supportive care is also crucial in AML treatment, including monitoring blood counts, managing infections, and providing blood transfusions as needed.
RECIST Criteria for Chemotherapy response in clinical trials
Measurable Lesions (Target Lesions):
These are lesions that can be accurately measured and tracked over time. RECIST 1.1 limits the number of target lesions to a maximum of five total, with a maximum of two per organ.
Non-Measurable Lesions (Non-Target Lesions):
These are lesions that cannot be reliably measured or tracked, or lesions that are followed qualitatively.
Target Lesion Measurement:
The longest diameter of each target lesion is measured in millimeters. The sum of these diameters represents the “tumor burden”.
Categorization of Response:
Complete Response (CR): Disappearance of all target lesions and reduction of pathological lymph nodes to <10mm short axis, according to the National Institutes of Health (NIH) | (.gov).
Partial Response (PR): A decrease of at least 30% in the sum of the longest diameters of target lesions.
Stable Disease (SD): Tumor burden does not meet the criteria for PR or PD.
Progressive Disease (PD): An increase of at least 20% in the sum of the longest diameters of target lesions, with a minimum increase of 5mm, or the appearance of one or more new lesions.
Confirmation of Response:
A response (CR or PR) must be confirmed by repeat imaging, typically 4 weeks or more after the initial response assessment.
Progression:
The appearance of new lesions or a 20% increase in the sum of the target lesion diameters, with a minimum increase of 5mm from the smallest recorded sum, indicates disease progression.
Non-Target Lesions:
These are assessed qualitatively, with any unequivocal progression leading to a PD designation.
Osteoporosis Therapies
Denosumab is a fully human monoclonal antibody that binds RANKL cytokine preventing RANKL from activating its receptor RANK on the osteoclast surface. With reduced RANKL-RANK binding, osteoclast recruitment, maturation and function are inhibited resulting in a decrease in bone resorption and an increase in bone mass.
Nitrogen-containing bisphosphonates (alendronate, ibandronate, pamidronate, zoledronic acid) all induce osteoclast apoptosis via inhibition of farnesyl pyrophosphate synthase (FPPS).
Raloxifene exerts anti-resorptive effects via modulating osteoprotegerin (OPG) expression in osteoblasts.
SMARCB1 marker
What is SMARCB1/INI1?
SMARCB1 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily B, member 1) is a gene located on chromosome 22q11.2.
It’s a component of the SWI/SNF chromatin remodeling complex, which plays a role in regulating gene expression by modifying chromatin structure.
Loss of SMARCB1 function can disrupt this complex and affect gene expression, potentially leading to uncontrolled cell growth and tumor development.
Tumors Associated with SMARCB1 Loss/inactivation
Rhabdoid Tumors:
These are highly aggressive tumors, both in the kidney (malignant rhabdoid tumor) and outside the kidney (extrarenal malignant rhabdoid tumor).
Atypical Teratoid/Rhabdoid Tumors (AT/RT):
These are rare, malignant brain tumors, often affecting infants and young children.
Other Tumors:
SMARCB1 loss is also observed in other cancers, including:
1. Sinonasal carcinomas: Specifically, basaloid carcinomas.
2. Gastrointestinal tract tumors: Including those in the pancreas and uterus.
3. Epithelioid sarcomas .
Some carcinomas of the lung and pleura .
Sellar tumors in adults .
Pancreatic undifferentiated rhabdoid carcinomas .
How is SMARCB1 Loss Detected?
Immunohistochemistry (IHC): This technique uses antibodies to detect the presence or absence of the SMARCB1 protein in tumor cells. Loss of staining indicates SMARCB1 loss.
Genetic Testing: This can be used to identify mutations or deletions in the SMARCB1 gene.
Clinical Significance:
Loss of SMARCB1 is associated with aggressive tumor behavior and poor prognosis in many cases.
It can be a useful diagnostic marker, helping to identify tumors that may be more aggressive or respond differently to treatment.
Research is ongoing to understand the specific mechanisms by which SMARCB1 loss contributes to tumor development and to identify potential therapeutic targets.
Birt-Hogg-Dube Syndrome
Birt–Hogg–Dubé syndrome is an autosomal dominant disorder caused by germline mutations in the tumour suppressor gene FLCN. It is associated with multiple bilateral pulmonary cysts, fibrofolliculomas, and multifocal and/or bilateral renal tumours of mixed histological types
Karnofsky Performance Scale
Karnofsky performance status
100% – normal, no complaints, no signs of disease
90% – capable of normal activity, few symptoms or signs of disease
80% – normal activity with some difficulty, some symptoms or signs
70% – caring for self, not capable of normal activity or work
60% – requiring some help, can take care of most personal requirements
50% – requires help often, requires frequent medical care
40% – disabled, requires special care and help
30% – severely disabled, hospital admission indicated but no risk of death
20% – very ill, urgently requiring admission, requires supportive measures or treatment
10% – moribund, rapidly progressive fatal disease processes
0% – death.
WHO Performance Scale
WHO performance status scores
0 –Asymptomatic (fully active, able to carry on all pre-disease activities without restriction).
1 – Symptomatic but completely ambulatory (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; for example, light housework, office work).
2 – Symptomatic, < 50% in bed during the day (ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours).
3 – Symptomatic, > 50% in bed, but not bedbound (capable of only limited self-care, confined to bed or chair 50% or more of waking hours).
4 – Bedbound (completely disabled, cannot carry on any self-care, totally confined to bed or chair).
5 – Death.
ECOG Performance Scale
ECOG Performance Status Scale
0 Grade - Fully active, able to carry on all pre-disease performance without restriction
1 Grade - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2 Grade - Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3 Grade - Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4 Grade - Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5 Grade - Dead
Mesna Drug
2-mercaptoethane sulfonate Na
Mesna is used therapeutically to reduce the incidence of haemorrhagic cystitis and haematuria when a patient receives ifosfamide or cyclophosphamide for cancer chemotherapy. These two anticancer agents, in vivo, may be converted to urotoxic metabolites, such as acrolein.
Mesna assists to detoxify these metabolites by reaction of its sulfhydryl group with α,β-unsaturated carbonyl containing compounds such as acrolein.[5] This reaction is known as a Michael addition. Mesna also increases urinary excretion of cysteine.
Hodgkin’s Lymphoma: Favourable Features
Age <50;
non-bulky disease (mediastinal to thoracic ratio less than 1/3);
absence of B symptoms;
3 or fewer lymph node regions involved;
and
normal ESR.
International Prognostic index for DLBCL
Risk factors:
- Age > 60 years
- Serum LDH > normal
- Stage III-IV
- Performance Status 2-4
- Extranodal sites > 1
Risk categories=Risk factors= Estimated 3 year overall survival (95%CI)
Low-risk = 0 - 1 = 91 (89 - 94)
Low-intermediate
risk = 2 = 81 (73 - 86)
High-intermediate = 3 = 65 (58 - 73)
High = 4 - 5 = 59 (49 - 69)
Lymphoma Tumor markers
A scoring system to distinguish CLL/SLL from other lymphoproliferative disorders is widely used based on CD5, CD23, CD79b, FMC7 and SmIg expression with 96.8% of patients with CLL/SLL scoring 4 or higher.
Diffuse large B cell lymphoma will be positive for CD3, CD10, BCL2 and BCL6.
Follicular NHL is CD10 positive.
Mantle cell lymphoma will be positive for CD3, CD10, cyclin D1, SOX11, BCL2 and BCL6. translocation of t(11;14) suggests the diagnosis is Mantle Cell Lymphoma
Marginal zone NHL will be positive for CD3, CD10 and cyclin D1.
Burkitt’s Lymphoma Markers
In Burkitt’s Lymphoma tumor cells express surface Ig of the IgM type and Ig light chains (kappa much more often than lambda), B cell-associated antigens (CD19, CD20, CD22, CD79a), germinal center-associated markers (CD10 and BCL6), as well as HLA-DR and MYC. They lack expression of CD5 and B cell leukaemia/lymphoma 2 (BCL2) and typically lack expression of CD23 and TdT.
Risk of Secondary Cerebral Lymphoma
The estimated incidence of secondary cerebral lymphoma is 5-8% although the introduction of rituximab into induction regimens appears to have reduced the incidence. However, it is estimated that ~20% of patients with:
i) A raised serum LDH AND more than one extranodal site (noting that the spleen is not regarded as an extranodal site and also, two lesions within the same system (e.g. bilateral lung lesions) are regarded as a single extranodal localisation).
OR
ii) Primary testicular, breast or epidural lymphoma will develop secondary cerebral lymphoma.
The present BCSH guidelines recommend primary prophylaxis with intrathecal methotrexate (IT MTX) despite the paucity of a randomised study confirming the efficacy of IT MTX in these patient groups.
Follicular Lymphoma International Prognostic Index (FLIPI)
Follicular lymphoma is the second most common subtype of non-Hodgkin’s lymphoma. It is generally recognised as being incurable but can remain indolent for periods.
The Follicular Lymphoma International Prognostic Index (FLIPI) was devised using data from a large number of patients with Follicular Lymphoma for 7 years and assesses patients using the following criteria:
= Age >60 years
= Stage III or IV
= Hemoglobin level <12.0>
= Number of involved nodal areas >4
= Serum LDH > than the upper limit of normal
High-risk FLIPI (three or more adverse factors) has a median PFS of 42 months, and a two-year OS of 87%, whereas, intermediate-risk FLIPI (two adverse factors) has a median PFS of 70 months, a two-year OS of 94% and low-risk FLIPI (zero to one adverse factor) has a median PFS 84 months, two-year OS 98%.
Reflection: The “remitting and relapsing” process of follicular lymphoma makes it difficult to predict how an individual’s disease will progress. Consider how patients with this disease can be psychologically supported through their cancer journey.
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