Umbilical ureteral carcinoma is a rare malignancy, which is less known to urologists because of its low incidence, and this article reviews the relevant domestic and international literature. I. Embryology, anatomy and histology The umbilical ureter is an embryonic structure located between the top of the bladder and the umbilicus. The vast majority of current knowledge on the occurrence, normal and abnormal anatomy of the umbilical ureter comes from the studies of Begg and Cullen. During the fifth embryonic week, the cloaca begins to separate, eventually forming the rectum on its dorsal side and the urogenital sinus and bladder on its ventral side. The bladder swells into an epithelial sac that tapers to a thin top and joins the urinary bladder at the umbilical level. There are two hypotheses to explain the occurrence of the umbilical ureter. One hypothesis suggests that the umbilical ureter originates from the upper part of the urinary bladder, while the lower part constitutes the bladder. However, the widely shared hypothesis is that the umbilical ureter originates in the cloaca, with the upper portion of the bladder joining the urinary bladder at the level of the umbilicus, which becomes narrowed as the lower portion of the bladder descends behind the pubic bone to form the umbilical ureter. In adults, the umbilical ureter passes between the transverse abdominal fascia and the peritoneum in the Retzius space and extends from the anterior top of the bladder toward the umbilicus. The umbilical ureter is approximately 5-5, 5 cm long, and a 3-cm segment of it is buried cephalad to the top of the bladder. The umbilical ureter is divided into an intramucosal segment, an intramuscular segment, and a supravesical segment. When the umbilical ureter is tubular, three subtle layers of tissue can be seen: (1) the cuboidal epithelium, or more typically the migrating epithelium; (2) the submucosal connective tissue layer; and (3) the outer layer of smooth muscle. The internal lumen is irregular, beaded, and filled with detached epithelial debris and epithelial islands. When the upper segment of the umbilical ureter metamorphoses into a fibrous cord, its internal structural components become unrecognizable. The pathogenesis of umbilical ureteral carcinoma is unclear. Some researchers believe that the metastatic epithelium in the umbilical ureter forms adenocarcinoma through metaplasia, and Culp hypothesized that because the bladder and rectum have a common germinal base in the cloaca, the dormant intestinal cells in the umbilical ureter can revert to an undifferentiated state and form mucus-secreting adenoid epithelium. Incidence Umbilical ureteral carcinoma is a rare tumor. Since Hue and Jacquin reported the first case of umbilical ureteral carcinoma in 1863, the number of cases with complete histological and clinical data in English literature does not exceed 150. In Western countries, the annual incidence of umbilical ureteral carcinoma is estimated to be 1 in 5,000,000 in the general population, accounting for 0,01% of all malignancies in adults, 0,17-0,34% of all bladder cancers and 20-39% of primary bladder adenocarcinomas [6]. At the time of presentation, 2/3 (68%) of patients were between 41-70 years of age (April-84 years), 65% of whom were male. Japanese scholars analyzed 157 patients collected in their country and found that the incidence of umbilical ureter accounted for 0,55-1,2% of all bladder cancers in Japan, which is higher than in Western countries, with 72% of men, and the age stage with the highest incidence was 50-60 years [7]. III. Histopathology The vast majority of umbilical ureteral carcinomas are mucinous or non-mucinous adenocarcinomas. Less common histologic types include sarcoma, metastatic cell carcinoma, and squamous cell carcinoma.Sheldon et al [1] counted 117 cases of umbilical ureteral carcinoma with 69% mucinous adenocarcinoma, 15% non-mucinous adenocarcinoma, 8% sarcoma, 3% squamous cell carcinoma, 3% metastatic cell carcinoma, and 2% unknown type. Ghazizadeh M [7] et al. reviewed 157 cases of umbilical ureteral carcinoma reported in the Japanese literature, of which 138 (88%) were adenocarcinoma, 5 (5%) were metastatic cell carcinoma, 3 (3%) were squamous cell carcinoma, 6 (4%) were undifferentiated carcinoma, and 5 (3%) were mixed type carcinoma. Non-mucinous adenocarcinomas include small cell carcinomas and other undifferentiated carcinomas of non-bladder epithelial origin. Mucinous adenocarcinomas are further classified into colonic cell type (the most common), glial type, and indolent cell type. Squamous cell carcinoma sometimes coexists with umbilical ureteral calculi and cysts [9]. The salient feature of umbilical ureteral sarcoma is the young age of onset, with 67% of patients younger than 20 years of age and 75% of patients younger than 20 years of age having sarcoma. There is no universally accepted histologic grading system, and Mostofi et al. have suggested that the pathologic diagnostic criteria for umbilical ureteral carcinoma are 1) tumor confined to the top of the bladder; 2) absence of adenoid cystitis and cystic cystitis changes in the bladder mucosa; 3) the main body of the tumor is located in the muscular layer or deeper tissue with a clear demarcation between it and the superficial bladder epithelium, and there is no glandular or polypoid hyperplasia of the superficial epithelium. 4) the tumor was visible in the residual umbilical ureter; 5) the tumor invaded the bladder wall and invaded the lower abdominal wall or umbilicus through the Retzuis space. Johnson et al. considered the criteria proposed by Mostofi et al. too restrictive, and they believed that as long as the tumor was located in the bladder wall and had a clear demarcation interface with the bladder mucosa, the diagnosis of umbilical ureteral carcinoma could be made when adenocarcinoma of other organs invading the bladder was excluded. Henly analyzed 38 cases of umbilical ureteral carcinoma and suggested that if the tumor is confined to the top or anterior wall of the bladder, the bladder mucosa is free of adenocystitis and cystic cystitis changes, and the tumor is visible in the remaining umbilical ureter, the diagnostic criteria of umbilical ureteral carcinoma are already in place. The prognosis of umbilical ureteral carcinoma is significantly worse than that of primary bladder adenocarcinoma [12]. One of the reasons is that the anatomical location is insidious, which determines that patients are often at an advanced stage when they are diagnosed, and most of them have already spread; the other is that umbilical ureteral carcinoma is often incompletely resected due to misdiagnosis, resulting in local recurrence after surgery. Early reports say that the 5-year survival rate of this disease is only 6.5%, and recent reports say it is 43%. Umbilical ureteral carcinoma is prone to local infiltration, most often invading Retzius space, peritoneum, abdominal wall and bladder. The extent and location of infiltration are related to the histologic type of the tumor, with squamous cell carcinoma and adenocarcinoma most frequently invading the bladder, while sarcoma mainly invades the peritoneum, abdominal wall and umbilicus, and less than half of the sarcomas invade the bladder. Local recurrence of umbilical ureteral carcinoma is particularly common after surgery. The most common sites of recurrence are the pelvis (21%), the bladder (16%), and the surgical incision and abdominal wall (6%). Local recurrence often occurs within 2 years after surgery (81%), and local recurrence is rare more than 4 years after surgery. in a study by David et al [15], of 38 patients with umbilical ureteral cancer, 15 (39%) had local recurrence at a mean of 1,8 years (0,2-5,3 years) after surgery, with a median time of 6 months. However, there are no reports in the literature on local recurrence in the bladder after partial cystectomy for umbilical ureteric sarcoma. Distant metastasis from umbilical ureteral carcinoma is usually a late manifestation. The most common sites of metastasis are lung, omentum, liver, bone, and iliac inguinal lymph nodes. Nakanishi et al. applied multivariate analysis on the prognostic factors of umbilical ureteral carcinoma, and the results showed that tumor stage and histological differentiation degree were strongly correlated with the prognosis of umbilical ureteral carcinoma and could be used as prognostic factors. V. Symptoms, signs and ancillary examinations The most common symptom of umbilical ureteral cancer is hematuria (64%), but the chance of occurrence is not the same among different histological types, among which the chance of occurrence is 0 for umbilical ureteral sarcoma and 71% for adenocarcinoma. Another common clinical presentation is a suprapubic mass, especially in sarcomas (64%), which may be its only feature. Other manifestations of umbilical ureteral carcinoma include abdominal pain, urinary irritation, and bloody or purulent discharge from the umbilicus, but all are less common. Mucinuria under the naked eye or microscope is a valuable clinical manifestation, which appears earlier than hematuria, but only 25% of patients have this manifestation, and it is not specific. VI. Diagnosis Umbilical ureteral carcinoma lacks specific clinical manifestations and is difficult to diagnose. Currently, it mainly relies on cystoscopy, ultrasound and CT for diagnosis. Although umbilical ureteral carcinoma with hematuria occasionally cannot be seen as any lesion under cystoscopy, in 88% of patients, tumors can still be found under cystoscopy, usually as localized bulges, flattened epithelial tumors, papillary or polyp-like masses, and sometimes streaky or bloody fluid can be seen spilling from the umbilical ureteral orifice. Therefore, any lesion presenting on the anterior or apical wall of the bladder should be of great concern to the cystoscopist. In contrast, a duplex examination under anesthesia is helpful in estimating the size and activity of the lesion. Transurethral biopsy usually confirms the diagnosis, but if this is not possible, an open biopsy with a rapid intraoperative frozen section is recommended to confirm the diagnosis. The most common imaging presentation of umbilical ureteral carcinoma is a filling defect and punctate calcification visible at the top of the bladder, which is one of the typical features of the disease. CT is useful to determine the size, degree of extravesical invasion and clinical stage of umbilical ureteral carcinoma, as well as to understand whether the tumor has recurred, which can compensate for the inadequacy of cystoscopy. This is because when the umbilical ureteral cancer has not yet invaded the bladder mucosa, cystoscopy can have no abnormal findings; secondly, the tumor on the top of the bladder seen by cystoscopy is often smaller than the size of the tumor on ultrasound or CT scan. On CT, the tumor consists of two parts: the intra-vesical portion and the supra-vesical portion. The supravesical portion has a cystic appearance with a vesicle encapsulating the tumor visible in the Retzius space; the intravesical portion that invades the top of the bladder is leech-like and not encapsulated by a vesicle. Some scholars also believe that MRI is superior to CT in early diagnosis and tumor staging of umbilical ureteral carcinoma because of its multiplanar imaging function and clear visualization of soft tissues in the tumor area. ultrasound is less accurate than CT and MRI, but intravesical ultrasound can make accurate judgment of lesion characteristics and infiltration extent of umbilical ureteral carcinoma, and this method is simple, economical and safe, which is recommended. It is important to distinguish primary bladder adenocarcinoma from umbilical ureteral carcinoma, which is difficult to do solely by cystoscopy and clinical presentation because about 15% of primary bladder adenocarcinoma occurs at the top of the bladder. It needs to be differentiated with the help of imaging techniques such as ultrasound and CT and tissue biopsy. In addition, adenocarcinoma of the primary rectum, stomach, endometrium, cervix, prostate and ovary can also present as a mass on the top of the bladder when local infiltration or metastasis occurs. However, this often occurs in the late stage of the primary disease, and the patient often has obvious symptoms of the primary disease, or has been diagnosed clearly by rectopelvic examination, sigmoidoscopy or barium enema examination. There are various clinical staging systems for umbilical ureteral cancer, and the most standard staging system is the one proposed by Sheldon et al. in 1984. Because of the insidious onset and local infiltrative growth of umbilical ureteral cancer in the early stage and the ease of metastasis in the late stage, about 83% of the patients have reached stage III when they are diagnosed. Treatment: The treatment methods of umbilical ureteral cancer include surgery, radiotherapy and chemotherapy. Among them, surgery is the main treatment. (1) Surgery: Ureteral cancer is prone to local recurrence, so the focus of surgical treatment is to control local lesions. However, the choice of surgical procedure is still controversial. Many authors advocate that all patients with umbilical ureteral carcinoma should undergo radical total cystectomy, which includes total cystectomy + umbilical ureteral tumor, anterior rectus fascia, part of peritoneum and umbilical whole resection + pelvic lymph node dissection; other authors believe that only some cases need radical surgery; recently, most scholars suggest that all cases should undergo extended partial cystectomy, which includes bladder Most recent authors recommend an extended partial cystectomy in all cases, including the top of the bladder, the transverse abdominal fascia, the umbilical ureter and part of the peritoneum along with the tumor. In the past, radical total cystectomy has been the procedure of choice, but in recent years there has been a preference for extended partial cystectomy, as the literature shows that radical surgery does not improve patient survival. Kakizoe et al. concluded that radical total cystectomy should be performed in all patients with umbilical ureteral carcinoma. They found a high rate of local recurrence after partial cystectomy for umbilical ureteral adenocarcinoma, with 37 out of 72 cases of umbilical ureteral adenocarcinoma recurring after surgery, a recurrence rate of 51%. However, in this group of cases, there was no significant difference in survival between patients who underwent total cystectomy and those who underwent partial cystectomy. Sheldon et al. concluded that most patients with umbilical ureteral carcinoma require radical total cystectomy, and only stage I tumors and umbilical ureteral sarcomas are suitable for partial cystectomy + umbilical ureterectomy. The rationale was that (1) the overall recurrence rate of umbilical ureteral cancer is 38%, of which 18% of patients who underwent partial cystectomy had intravesical recurrence, and this recurrence was ineffective by reoperation and radiotherapy, so the first operation must be complete; (2) intravesical recurrence after partial cystectomy for umbilical ureteral sarcoma has not been reported. However, two of the five patients they reported who underwent radical total cystectomy died postoperatively, whereas all three patients who underwent partial cystectomy survived. Most of the recent literature advocates the use of extended partial cystectomy with similarly good results. For example, Herr advocates partial cystectomy for all patients with umbilical ureteral carcinoma. In a group of 12 patients with adenocarcinoma of the umbilical ureter who underwent an extended partial cystectomy, 8 survived tumor-free for more than 2 years and up to 13 years. Patients who underwent partial cystectomy had longer tumor-free survival and higher 5-year survival rates than those who underwent radical total cystectomy. Ma et al. reported 12 cases of umbilical ureteral carcinoma, 7 of which underwent extended partial cystectomy and none of which had local recurrence after surgery. It is believed that extended partial cystectomy can be the first choice for umbilical ureteral adenocarcinoma, which improves patients’ quality of life without affecting their survival rate, and at the same time, the thoroughness of the first surgical treatment is especially emphasized, and the tumor in the bladder cavity should not be used as the standard for partial cystectomy, otherwise it is very likely to cause postoperative recurrence due to inadequate tumor resection. (ii) Radiotherapy: At present, the role of adjuvant radiotherapy is still unclear. Henly et al [15] gave adjuvant radiotherapy to the pelvis in 12 patients, and the survival rate did not improve significantly. sheldon [1] et al reviewed 8 patients who had radiotherapy in the literature and found that all patients died of cancer. They concluded that radiotherapy may have some efficacy in patients with advanced disease, for example, one patient with undifferentiated stage IVB survived 8 years after radiotherapy and another survived tumor-free for up to 6 years after radiotherapy for recurrent umbilical ureteral adenocarcinoma. In 1/3 of the patients, recurrence occurred within 3 years after partial cystectomy + adjuvant radiotherapy and survival was possible for another 2 or 5 years after continued radiotherapy. Nevertheless, they still believe that most patients with umbilical ureteral cancer are not sensitive to radiotherapy. (iii) Chemotherapy: chemotherapy has a certain effect on metastatic umbilical ureteral carcinoma. Ma Jianhui et al. performed chemotherapy on 6 patients with postoperative recurrence or metastasis, and 2 cases were in partial remission with an effective rate of 33%. They believed that combined chemotherapy with 5-fluorouracil, mitomycin, cisplatin and adriamycin mainly has certain efficacy on umbilical ureteral adenocarcinoma. However, seven cases reported by Henly et al. did not show significant effects after receiving a 5-fluorouracil-based chemotherapy regimen. To date, the exact value of chemotherapy is not certain and further information needs to be accumulated. IX. Summary: Umbilical ureteral carcinoma is a rare malignant tumor. It has a poor prognosis because of its insidious location, long latent period, easy extra-vesical infiltration and local recurrence. The most common histological type is adenocarcinoma, most of which can secrete mucus, which is helpful for diagnosis. Common symptoms include hematuria, abdominal pain, urinary irritation and abdominal masses, but are not specific. Diagnosis relies mainly on cystoscopy and imaging. The most typical imaging features are filling defects and punctate calcifications visible at the top of the bladder. The tumor can often be seen on cystoscopy at the top of the bladder or in the anterior wall, and a biopsy can confirm the diagnosis. As long as the tumor is confined to the top or anterior wall of the bladder, the bladder mucosa is free of adenoid cystitis and cystic cystitis changes, and the tumor is visible in the residual umbilical canal, the diagnostic criteria for umbilical ureteral carcinoma have been met. It is very difficult to distinguish primary bladder cancer from umbilical ureteral cancer, which is difficult to be done solely by cystoscopy and clinical manifestations. There are various clinical staging systems for umbilical ureteral cancer, and the current accepted staging system was proposed by Sheldon in 1984. The main point of treatment for umbilical ureteral carcinoma is to control local lesions, and surgery is the main treatment. The choice of the surgical procedure is controversial, and since the literature shows that radical total cystectomy does not improve the survival rate of patients, extended partial cystectomy is increasingly being advocated. As for radiotherapy and chemotherapy, the exact value is not certain as little experience has been accumulated. The results of multivariate analysis showed that tumor stage and histological differentiation degree were closely correlated with the prognosis of umbilical ureteral carcinoma and could be used as prognostic factors.