Essay on Pathophysiology of Lung Cancer

Case Scenario Presentation

Nancy Lerner is a 75-year-old woman who visited the health facility complaining of shortness of breath, fatigue, productive cough, and chest pain. On examination, she also indicated she had experienced a drastic weight loss of about 13 pounds within one month. Her medical history showed she has struggled with hypertension for a prolonged duration. She works as an educator in a technical college. On inquiring about her smoking habits, she reiterated she started smoking at the age of 20, thus having a 55-year history. Despite the length of engaging in this habit, she consumed at least three cigarettes a day. She is a wife and a mother of 4 children. The physical exam indicated a decrease in her breath sounds and dull percussions. Next, she underwent an x-ray scan. This examination showed her 5.2 cm mass in her left upper lobe and a hilar mass as well. To further diagnose the patient, a CT scan was conducted. This test revealed the mass had a mediastinal extension moving bilaterally. The fourth test was a PET scan. From this evaluation, it was deduced that there was activity in the liver lesions and left lobe activity verified by the interventional radiographic assessment, which categorized her PS at one and positive for SCLC.

Definition and Types of Lung Cancer

Lung cancer accounts for 12% of all cancers reported globally. In the global population, it is the second popular form of cancer for both men and women having a higher presentation in the United States of America (Braillon, 2018). This condition can present as small cells lung cancer, which constitutes a wide range of other carcinoma subtypes. Its origination is linked to the lymphatic system due to the similarities observed between lymphoma and SCLC cells (Kastelik, 2020). This form is malignant and consists of minute cells characterized with inconspicuous/absent nuclei, scanty cytoplasm, granular chromatin, and unrefined cell boundaries. The lung is the origin location for 95% of these small cells (Braillon, 2018). However, other sources include the gastrointestinal tract, nasopharynx, and extrapulmonary tract. There is a clear differentiation when comparing lung carcinomas observed from different sources. For instance, when comparing extrapulmonary SC carcinoma with pulmonary alternative, the former does not elicit 3p gene deletions.

Pathophysiology

When reviewing the causative agents contributing to the onset of SCLC, chromosomal abnormalities are presented as primary agents. These biological events are observed in a high percentage of epithelial tumors which point to genome instability. The deletions evident in SCLCs have a damaging impact on the chromosomal sites causing the loss of 3p, 13q, 17p, and 5q (Kastelik, 2020). These deletions are critical in facilitating this disease as the four genes function to prevent tumor formation due to their suppressive nature. Additionally, their removal allows for gene encoding for oncogenes include KRAS and MYC. It is also important to mention the allele loss which occurs and is considered a key event in the onset of SCLC. According to research, this happens on chromosome 3p, with several chromosomal sites affected, such as 3p12, 3p24, and others (Kastelik, 2020). The damage on these genes that possess tumor-suppressive qualities further limits their expression in epigenetic processes. The second abnormality includes the deletion of the fragile histidine triad. They are contained in the 3p14 gene and are subject to deletion in 100% of reported SCLCs cases. Its expression is halted based on its role in regulating death receptor genes therefore considered formidable in eradicating tumor-causing cells. This process involved the RARβ gene methylation catalyzed by SCLC hence destroying its expression.

The third abnormality involves disruption of telomerase activity. In definition, this unit is comprised of recurring sequences placed at chromosome endpoints (Braillon, 2018). The sequencing unit reads (TTAGGG). During the cell division process, there is a partial loss of this unit. However, due to its dependency on RNA, as a DNA polymerase, it can generate new sequences to compensate for the lost units. The newly synthesized repeats occur during replication, with each unit containing a telomerase unit and hTERT subunit. The pathophysiology of SCLC silences the functionality of this unit (Kastelik, 2020). This effect happens when the cells engage in a continued and infinite division, signaling cell immortality (Braillon, 2018). This effect is achieved by reactivation of telomerase activity which focuses on replacing the lost genetic repeats. Studies justify this activity as they show an increased telomerase and hTR activity.

SCLC affects several signaling pathways to reduce any combative effects against tumor growth (Kastelik, 2020). One of the affected pathways includes the phosphoinositide three kinases (PIK3s), constituting lipid proteins kinases (Braillon, 2018). Their primary functions cover cell differentiation, proliferation, motility, adhesion, and survival. The central stimulators that cause a cascade of events within these pathways include two receptors with g protein receptors and tyrosine kinase. However, the PIK3s pathways become defective in an SCLC diseased condition due to its production of PTEN, a tumor suppressor gene whose role is a negative regulator (Braillon, 2018). This silencing is primarily caused to induce the PTEN and PIK3 mutations genes in the SCLC cells to generate phosphorylated AKT and 4E binding protein.

Symptoms

Lung cancer often remains undetected for a prolonged period hence considered asymptomatic in its early stages. However, the condition might be prolonged for a considerable period leading to further degeneration, causing more damage to the affected person. The minimal pain fibers in the parenchyma support this observation; therefore, the condition only becomes noticeable when the tumors grow into considerable size. Studies indicate that 5% of the total population of lung cancer patients do not present symptoms (Kastelik, 2020). Often, this diagnosis is revealed when treating an unrelated condition or when a patient requests a radiograph when undergoing a preoperative assessment. The first symptom is cough in symptomatic cases, seen in 70-90% of cases reported (Kastelik, 2020). It Theion. In addition, it can also emanate from an existing small tumor in symptomatic patients, which causes irritability through bronchial ulceration. In such scenarios, it is a direct indicator of carina invasion by peripheral tumors enlarging.

Hemoptysis occurs when a patient coughs blood either in the form of tainted sputum or a clot. This symptom is associated with bronchial ulceration in the mucosa. In most instances, it is minimal. The automatic period that tainted sputum is first witnessed leads to a probable consideration of necessary action to stem the sudden occurrence on the individual. However, some patients experience significant effects with up to 200 ml of blood observed. This sign shows the individual is experiencing venous rupture in their bronchi. Therefore, it is imperative to monitor this clinical manifestation in terms of duration, frequency, and amount to determine the regimen applicable to manage it (Braillon, 2018). Dyspnea is the third system in 58% of reported lung cancer incidents (Braillon, 2018). It is an early clinical sign which is primarily associated with smoking. Its presentation can either be due to an endobronchial obstruction caused by a tumor or positional (Ott, 2019). Therefore, it is essential to conduct a physical and biochemical assessment to ascertain lung cancer diagnosis. This action is necessary because dyspnea also occurs in pleural effusion, coincidental pneumonia, and bronchopulmonary infections.

Risk Factors

A myriad of risk factors is associated with the onset of lung cancer. They comprise both lifestyle and environmental factors. Cigarette smoking is significantly linked to this condition, with a 90% causative influence in all cases reported globally. According to statistics, a person with smoking cigarettes daily is at a 20% higher risk than a non-smoker (Ott, 20190. The severity of this condition in its manifestation is determined by an individual length of exposure to cigarette smoke and other carcinogenic elements, including asbestos. In patients presenting with other malignancies and on treatment, radiotherapy is perceived as a risk as it can catalyze the onset of secondary primary lung carcinoma (Braillon, 2018). Empirical explorations demonstrate that in patients with mastectomy under treatment, if subjected to RT, the risk of developing lung cancer as a secondary condition is higher. This effect is amplified in individuals diagnosed with Hodgkin lymphoma and pronounced tumors in the ipsilateral lung.

Treatment Types

An integral treatment plan proposed for a patient with small cell lung cancer is the cessation of smoking. Patients who experience difficulty in independently quitting the habit are referred to a specialist who offers assistance in facilities such as smoking clinics. In addition, the thought process behind it is the need to curtail the spread of limited aeration supply to the affected lungs. The primary justification for promoting this strategy is the agitation induced by smoking that affects oral mucositis hence caused reduced sense of taste, weight loss, xerostomia, and lethargy (Ott, 2019). Its effectiveness is observed in patients who complete the treatment. According to studies conducted on this population, they report better moods, sleeping patterns and energy, and minimal dyspnea and fatigue (Braillon, 2018). Another health issue associated with smoking, mainly when an individual is under radiotherapy, is extensive pneumonitis which is likely to develop. Therefore, focusing on integrating healthier habits to replace this detrimental one is elemental in circumventing the likelihood of such ramifications (Ott, 2019). It is important to note that any occurring relapses further complicate the recovery process for the patient as they can cause the onset of second primary tumors. The subsequent effect is a less impressive prognosis compared to those who quit smoking.

Chemotherapy is recommended for patients as an appropriate treatment. One common type is adjuvant chemotherapy, which is applicable for individuals treated via surgical resection. However, in some cases where the patient is in the advanced stages of the disease, chemotherapy is applied singularly. In unique scenarios, radiotherapy is included in those with palliative symptoms (Ott, 2019). Another instance to consider is patients who have developed brain metastases alongside SCLC. For these individuals, whole-brain radiotherapy is recommended on whether the patient is presenting neurological symptoms. Effective types of chemotherapy include combination and single-agent regimens with the application of cisplatin and etoposide in the former (Ott, 2019). For higher efficacy, an anthracycline-based regimen is applicable due to its toxicity and effectiveness in progressive stages. To reduce neuropathy when rendering treatment, replacing the agent is deemed necessary, whereby cisplatin is used instead of the ones mentioned above.

Radiotherapy is the third form of treatment effectual in a select group of patients. Research particularly randomized trials indicate this regimen works well in instances where a patient has achieved progressive results with chemotherapy and exhibits low bulk metastates. Individuals with these characteristics are subjected to hyper-fractionated radiotherapy (Kastelik, 2020). The second regimen is known as PCI. It is applied in patients diagnosed with intracranial metastases. This condition is estimated to occur in 50% of SCLC (Braillon, 2018). The therapy is preferred in cases with such manifestations due to its reductive efficacy on cerebral metastases (Ott, 2019). In addition to this, it also limits the emergence of these tumors. Before administrating this treatment, the physician and the patient must engage in a balanced discussion and reach an agreement on the same (Kastelik, 2020). Also, it is necessary to ensure information sharing is done, such as the toxic aftereffects such as nausea, fatigue, vomiting, and headache.

Palliative care provision is another treatment measure effectual inpatient experience symptomatic manifestation of the disease including obstructive atelectasis, spinal cord pressure, and pain-inflicting lesions (Skrzypski & Jassem, 2018). It is accompanied by orthopedic stabilization in instances where the patient is at the risk of fracturing a bone which might lead to osseous impairment (Kastelik, 2020). Palliative care is also combined with whole-brain radiotherapy in cases where the patient develops multiple metastases despite the resulting probable complications, including neurocognitive incapacitation.

References

Braillon, A. (2018). Second-line therapy and advanced non-small cell lung cancer: What about smoking? Lung Cancer, 122, 257. doi:10.1016/j.lungcan.2018.05.017

Kastelik, J. (2020). Diagnostic approach to lung cancer. Frontiers in Lung Cancer, 3(2), 85-113. doi:10.2174/9789811459566120010007

Ott, P. A. (2019). Immunotherapy in cancer, an issue of hematology/Oncology clinics of North America, Ebook. Elsevier Health Sciences.

Skrzypski, M., & Jassem, J. (2018). Consolidation systemic treatment after radiochemotherapy for unresectable stage III non-small cell lung cancer. Cancer Treatment Reviews, 66, 114-121. doi:10.1016/j.ctrv.2018.04.001