​Kembara Xtra - Medicine - Bladder Cancer

​Kembara Xtra - Medicine - Bladder Cancer 

Introduction
Primary malignant neoplasms of the bladder that are cancerous 
The three forms, transitional cell carcinoma, squamous cell carcinoma, and adenocarcinoma, all start in the cells that line the bladder.
Transitional cell carcinoma makes about 90% of cases.
Rhabdomyosarcoma of the bladder may develop in children. Bladder cancer can be non-muscle invasive, muscle invasive, or metastatic in nature.

Incidence and prevalence in Epidemiology 

Males are more likely to get the condition than females (4:1), while the risk is 1:1 in smokers. Incidence Rises with age (median age at diagnosis is 73 years) Is more frequent in Caucasians than Asians or African Americans.
19.7/100,000 men and women combined per year, 34.2/100,000 men per year, 8.5/100,000 women per year, and
Prevalence
There were 723,745 cases in the US in 2018.

Etiology and Pathophysiology 
Unknown, besides its connection to risk factors:
75% of cases are non-invasive to the muscle (in lamina propria or mucosa): - Most often very differentiated and long-lasting
- In superficial tumors, an oncogene on chromosome 9 appears to be activated as the first event.
At presentation, 25% of tumors are muscle invasive (deeper than lamina propria): - Often high grade and have a poor prognosis - Linked to additional chromosomal losses
Genetics
It's possible that genetic factors directly contribute to the development and spread of bladder cancer. The majority of research revealed a somewhat elevated risk in close relatives of bladder cancer patients.
Up to 20% of patients with Lynch syndrome will get bladder cancer in their lifetime.

Risk Factors Smoking is the single biggest risk factor, increasing risk by four times and having an equal impact on men and women.
Pioglitazone use carries a small but considerable elevated risk, presumably dose- and time-dependent; this risk may also be present with other thiazolidinediones.
Additional risk factors include: - A positive family history, particularly if relatives were diagnosed before the age of 60; Schistosomiasis in Mediterranean (squamous cell) cancer - Occupational carcinogens in dye, rubber, paint, plastics, metal, carbon black dust, petroleum, and vehicular exhaust -
- Well water containing arsenic
- A history of pelvic irradiation, bladder radiation, or the use of certain anticancer medications, such as cyclophosphamide or ifosfamide - A chronic lower urinary tract infection - A chronic urinary catheter - A history of cyclophosphamide exposure

Smokers should have a cystoscopy to check for bladder tumors if they have microscopic or gross hematuria or irritable voiding symptoms like urgency and frequency that aren't definitely caused by a urinary tract infection.


Preventative measures include avoiding risky behaviors like smoking and alcohol consumption.
According to the U.S. Preventive Services Task Force, there is not enough data to weigh the benefits and risks of screening for bladder cancer.

Smoking is an associated condition.

The most frequent symptom is painless hematuria, followed by urinary symptoms (frequency, urgency, and dysuria), and, in cases of severe disease, abdominal or pelvic pain. 
● Exposures

clinical assessment
Early cases are normal, later cases have pelvic or abdominal mass, and systemic disease causes wasting

UTI, nephrolithiasis, interstitial cystitis/nephritis, papillary urothelial hyperplasia, renal cell carcinoma, and other urinary tract neoplasms are among the various diagnoses.


Examinations and diagnostic procedures
Initial examinations (lab, imaging)
The first test performed on individuals who have gross hematuria or urinary symptoms including frequent urination, urgency, or dysuria is a urine analysis.
Cytology of urine (ask your local lab for the volume needed and the right fixative/handling.) 
The gold standard for at-risk patients with painless hematuria is cystoscopy with biopsy.
To ascertain the histologic grade and depth of invasion, transurethral resection of the bladder tumor (TURBT) is necessary. A CT or MRI at the time of TURBT is advised to rule out subsequent main lesions and is useful in staging.

Tests in the Future & Special Considerations
34-55% sensitive, >90% specific urine cytology
Urine-based tumor markers: specificity is between 70% and 90%, and sensitivity is between 50% and 80%.
None of the urine markers, however, are sensitive enough to definitively rule out bladder cancer, thus they are not advised for use in regular testing.
- The efficacy of intravesical Bacillus Calmette-Guérin (BCG) therapy can be predicted and evaluated using the Fluorescence in Situ Hybridization (FISH) assay. 
If metastasis is suspected, liver function tests and alkaline phosphatase should be done. 
Done for staging and assessing the severity of the disease but not for the actual diagnosis: - If there is a suspicion of disease in the upper tracts, a CT urogram should be used instead of an IVP. - Studies are being conducted on the use of diffusion-weighted MRI and multidimensional CT scan for the diagnosis and staging of bladder tumors.
– Metastatic workup for invasive disease should include a chest x-ray and PET scan.
– If the patient experiences bone pain or if their alkaline phosphatase level is elevated, a bone scan should be done.
If metastasis is suspected, a urologic CT scan (abdomen, pelvis, with and without contrast) or MRI (40-98% accurate), with MRI being somewhat more accurate, is advised.
After TURBT and intravenous chemotherapy, routine cystoscopy (started 3 months after the procedure) is advised for superficial bladder malignancies. It is not recommended to routinely employ urinary biomarkers for follow-up.

Test interpretation: Lesions that are superficial (nonmuscle invasive) or invasive (muscle invasive) account for 70–80% of all lesions.
Noninvasive papillary cancer has a propensity to come back.
- This is a flat lesion with a high grade cancer in situ.
- T1: penetrates the lamina propria and submucosa. typically high caliber
Invasive cancer: T2: muscle invasion; pT2a: superficial muscle invasion; pT2b: deep muscle invasion; T3: perivesical fat invasion; pT3a: microscopic; pT3b: macroscopic
T4 causes an invasion of nearby organs; T4a causes an invasion of the prostate, uterus, vagina, or colon; T4b causes an invasion of the abdominal wall, pelvic wall, or other organs.
M: metastases to bone or soft tissue N1 to N3: invades lymph nodes

Management 

Treatment for nonmuscle-invasive bladder cancer consists of a full TURBT and one dose of intravesical chemotherapy; the need for further intravesical chemotherapy will depend on the likelihood of recurrence and progression. A radical cystectomy with pelvic lymphadenectomy is preferable for muscleinvasive cancer. In a recent Cochrane analysis, open radical cystectomy and robotic radical cystectomy were compared, but no discernible changes were found in the rates of serious complications, the quality of life, or the rates of positive margins.

The First Line of Medicine
For low-risk superficial lesions, one quick intravesical chemotherapy installation (such as mitomycin, epirubicin, or gemcitabine) is advised after TURBT.
Chemotherapy is the first-line treatment for metastatic bladder cancer: - Methotrexate, vinblastine, doxorubicin, cisplatin (MVAC) is the preferred regimen. - Six-week induction course of intravesical BCG or Mitomycin C after TURBT in high-risk superficial lesions has been shown to decrease recurrence and delay disease progression.
Next Line
Checkpoint inhibitor immunotherapy is favored for patients who progressed following platinum-based therapy, according to a recent review, which also suggested that gemcitabine with cisplatin would be more tolerable and produce an equal survival rate to MVAC.

Sources of Referral 
Refer patients to a urologist for a cystoscopy if they have microscopic or gross hematuria that cannot be otherwise explained or resolves.

Furthermore Treated 

Patients with muscleinvasive cancer who are not candidates for surgery or who want to retain their native bladder undergo radiotherapy in the United States.
 Preoperative radiation (radical cystectomy) is another choice.

Surgical Techniques 
Surgery is the only effective treatment for both invasive and superficial cancer:  TURBT for superficial cancer
 Cancer that is invasive
- The gold standard is bilateral pelvic lymphadenectomy and radical cystectomy.
- In some circumstances, partial cystectomy may be a possibility.
- Men may need a prostatectomy, while women may need a full hysterectomy and bilateral salpingo-oophorectomy. 

Admission Required for Intensive Therapy or Surgery


Urine cytology has not been proven to be sufficient for follow-up in cases of superficial malignancies.
- Cystoscopy every three months for 18 to 24 months, then every six months for the following two years, and finally once a year.  
How invasive tumors are treated affects the need for follow-up care.
BCG patients need to be monitored for the rest of their lives.
DIET
Continue to drink enough water.
Quitting smoking

The prognosis is determined by the cancer's stage, grade (how the cells appear under a microscope), the existence of carcinoma in situ in other bladder regions, the patient's age, and overall health.
The overall survival percentage was 77.1% after five years.
In-place: 96.0%
69.6% of it is local.
Metastasis in the region: 37.5%
Remote metastasis: 6.4%
The prognosis for superficial bladder cancer varies on the size, number, and location of the tumors as well as if they returned following treatment.
– In comparison to TURBT alone, a single immediate intravesical chemotherapy installation following TURBT reduces tumor recurrence by 10-15%; BCG treatment lowers the risk of recurrence and advancement in high-risk superficial lesions.
Radical cystectomy yields a 60–75% 5-year survival rate for invasive carcinoma with T2 illness.
- Radical cystectomy yields a 20–40% 5-year survival rate for T3 or T4 illness.
- Neoadjuvant chemotherapy combined with cystectomy has increased survival to variable degrees.
- Radiation combined with chemotherapy has increased survival to varied degrees.
The median survival time for MVAC patients with metastatic cancer was 12.5 months.

complications Local symptoms of superficial bladder cancer
Dysuria, frequent urination, nocturia, discomfort, and passing urine with debris are all signs of bacterial cystitis.
A flu-like illness
 Systemic illness
Invasive cancer patients are at risk for azotemia and metabolic acidosis because they have neo bladders, which can cause incontinence and bleeding during therapy.