Editing Upper Urinary Tract Urothelial Cancer (section)

== Risk Factors ==

=== <strong><span style="color:#ff0000">Hereditary (1)</span></strong> ===
# <strong><span style="color:#ff0000">[[Lynch syndrome]] (hereditary nonpolyposis colorectal carcinoma (HNPCC))</span></strong>
#* <strong>Compared with non-hereditary cancers, patients are younger (mean age 55 years) and are more likely to be female</strong>

=== <span style="color:#ff0000">Acquired (8)</span> ===
* '''<span style="color:#ff0000">Risk factors shared with bladder cancer (7)</span>'''
*# '''<span style="color:#ff0000">Cigarette smoking</span>'''
*#* '''<span style="color:#ff0000">Most important modifiable risk factor for UTUC</span>'''
*#* Smoking cessation decreases subsequent risk
*# '''<span style="color:#ff0000">Occupational exposure</span>'''
*#* '''Exposure to aromatic hydrocarbons''', especially those used in the chemical, petrol, and plastic industries; other occupations at risk are those with exposure to coal, asphalt, or tar
*# '''<span style="color:#ff0000">Chronic inflammation, infection, or iatrogenesis</span>'''
*#* Chronic bacterial infection associated with urinary stones and obstruction has been associated with the development of squamous cell cancer (and less commonly adenocarcinoma)
*# '''<span style="color:#ff0000">Alkylating chemotherapy</span>'''
*#* '''Cyclophosphamide''' or ifosfamide
*# '''<span style="color:#ff0000">Analgesic abuse</span>'''
*#* Phenacetin is the most well described causative agent in analgesic nephropathy, others include codeine, acetaminophen, and aspirin.
*#* The number of cases attributed to phenacetin has decreased since phenacetin was replaced by its non-toxigenic metabolite acetaminophen
*#'''<span style="color:#ff0000">Arsenic</span>'''
*#* Exposure can be from drinking water from artesian wells
*#'''<span style="color:#ff0000">History of bladder cancer</span>'''
*#* '''Primary upper urinary tract tumors are uncommon'''
*#**'''Most UTUC occur as secondary tumors that present after NMIBC'''[https://pubmed.ncbi.nlm.nih.gov/11956428/]
*#*'''<span style="color:#ff0000">2-4% patients with bladder cancer will subsequently develop UTUC</span>'''
*#**Interval ranges from 17-170 months
*#**'''Risk factors for subsequent UTUC in patients undergoing cystectomy for bladder cancer[https://pubmed.ncbi.nlm.nih.gov/23083867/]'''
*#***'''Low-grade tumors'''
*#***'''Non–muscle invasive tumors'''
*#***'''N0 status'''
*#***'''Presence of CIS'''
*#***'''Multiple urothelial recurrences'''
*#***'''Multifocal tumors'''
*#***'''History of previous UTUC'''
*#***'''Positive ureteral margin'''
*#***'''Involvement of male prostatic urethra or female urethra'''
*#**** Based on meta-analysis of 27 studies with 13,185 patients (Picozzi et al, 2012)
*#** '''Long-term surveillance of the upper tract is important in bladder cancer patients'''
* '''<span style="color:#ff0000">Unique to UTUC (1):</span>'''
*# '''<span style="color:#ff0000">Aristolochic acid</span>[https://pubmed.ncbi.nlm.nih.gov/23462915/]'''
*#* Found in plants (Aristolochia fangchi and Aristolochia clematitis) and has mutagenic action; the associated mutation is predominant in patients with Balkan endemic nephropathy and Chinese herb nephropathy. These plants are endemic in Balkan countries and grow as weeds in wheat fields. The incidence of Balkan endemic nephropathy is decreasing.