Genitourinary cancer Urachal cancer part 3

Proper management of urachal carcinoma surgical requires that the diagnosis was made preoperatively on the basis of recognition of this possibility in the appropriate clinical setting. Before read this part, please read Genitourinary cancer Urachal cancer part 2 . Cross-sectional images are the key to recognize the diagnosis. On CT, urachal carcinoma usually appears as a mass of low attenuation in the dome of the bladder, usually in the midline or slightly to one side. Due to the relatively high rate of recurrence after treatment of this disease, the resection of the umbilicus, urachus, covering the peritoneum and posterior rectus fascia lateral to the medial umbilical ligament, bladder, and lymph nodes of the pelvis is now normal. The recognition that urachal tumors are predominantly extravesical and is not associated with a defect in the camp suggested to surgeons that in most cases, even bulky tumors could be completely resected with adequate margins and en bloc dissection only a partial cystectomy. Contemporary series report that neither local recurrence nor result threatened by this approach. On the contrary, survival is rather linked to the stage of presentation, presence of metastases in lymph nodes, and the ability to achieve a negative surgical margin with the completion of a partial or total cystectomy. Radical cystectomy is indicated for salvage surgery to treat a positive surgical margin, or delete a ligament from inadequate control of urachus - which occurs when the diagnosis was made before the operation. In a series of patients referred to MD Anderson Cancer Center is remarkable that only 19 of 35 patients undergoing primary surgical treatment was resection of the urachal ligament and umbilicus. The importance of adequate surgical treatment was reinforced by the finding that 13 of the 16 long-term survivors referred to in this series were treated with en bloc resection including umbilectomy.

Unfortunately, patients with lymph node or peritoneal discovered in surgery have a median survival of about 25 months, and demonstrate a clinical course that is virtually indistinguishable from that of patients with clinically evident metastases at diagnosis. In view of this finding, and demonstrated benefit of perioperative chemotherapy for colorectal cancer, the use of adjuvant or neoadjuvant chemotherapy for urachal cancer appears to be a reasonable consideration. Unfortunately, there are essentially not affect the data on this point directly, so we were left to extrapolate from our experience with other intestinal adenocarcinomas. Since we have some systemic therapies with clinically relevant response rates (see below), it seems appropriate to discuss adjuvant therapy in patients at high risk of recurrence, even those with tumors in the lymph nodes or peritoneal surface, or in the environment of inadequate surgery, including the presence of positive margins and in the scenario where the urachal ligament was not controlled.

As expected, few long-term survivors were observed after developing metastases. The sites most frequently involved are the bones, lungs, liver, lymph nodes and brain. Peritoneal carcinomatosis is common, especially in the context of positive surgical margins and when the peritoneal implants are present in the cystectomy.

Historically, chemotherapy has had little impact on the treatment of urachal cancer. This is particularly true in the context of traditionally used chemotherapy regimens for TCC. More recently, the responses have been reported in the establishment of schemes of 5-fluorouracil-based chemotherapy. Today, they are enrolling patients in a Phase II trial of combination chemotherapy with 5-fluorouracil, leucovorin, gemcitabine and cisplatin. The results in the first 20 patients showed an objective response in just over a third of patients. According to the clinical manifestations of this disease is so closely related to colorectal cancer, anecdotal responses have been observed in patients treated with capecitabine and irinotecan-based regimens, and the antibody cetuximab antiepidermal growth factor.

Genitourinary cancer Urachal cancer part 1

It is estimated that one case of urachal carcinoma for every 600 patients treated for bladder cancer. The urachus is a vestigial structure, which while important in some species, has no role in the development of human beings. The precursor initially urachal ligament arises from the cloaca at the end of the large intestine. During embryogenesis, the cloaca is divided to form the urogenital sinus, which develops in the bladder and sexual organs, and the anorectal canal, which becomes the rectum. The bladder is formed from the medial part of the urogenital sinus. Superior to this, in light of the allantois is obliterated to form the urachus. In adulthood, the urachus is attached to the obliterated umbilical arteries to form the commune of ligament. Although urachal ligament is most often connected with the dome of the bladder, can also attach to the back wall of the bladder or earlier, usually in the midline. A light remnant may persist in the bladder wall in the form of small tubular or cystic structures, and can communicate with the light of the bladder in up to one third of adults. Columnar cells, glandular islands, and the transitional cell epithelium may be present in a urachal remnant. When the malignancy is found to arise from this remnant, histology is the overwhelming intestinal adenocarcinoma.

Two theories have been proposed for the development of tumors of the urachus. One of them is that they come from intestinal adenocarcinomas is based on the left behind the cloaca during embryological development. This explains the histological similarity to adenocarcinomas of the rectum. An alternative hypothesis is that these tumors arise from metaplasia. Supportive evidence includes the occurrence of adenocarcinomas of the bladder epithelium despite exstrophic transition at birth, the occasional development of other tumors of intestinal type in the ureter and renal pelvis, which are not of sewage, and observation of adenocarcinoma arising from glandular cystitis.

What the details of its origin, it is clear that these types of cancer have a clinical manifestation that is very different from typical urothelial cancer. No risk factors have been identified, and in particular, smoking and other environmental factors figure prominently in the typical CTP do not seem relevant. Patients with cancer of the urachus are usually much younger, with a mean age of 47 to 57 years reported at diagnosis, with many cases reported in the third and fourth decades. In addition, these cancers occur equally in men and women (male / female ratio of TCC is approximately 3: 1), and show less susceptibility to cisplatin-based chemotherapy.

Most urachal tumors intestinal histology type display, similar to adenocarcinomas of the colon and rectum. These tumors are usually glandular structures with mucin production, colloid and / or histology of signet ring cells can be present.More rarely sarcomatoid carcinoma, and transitional cell histology have been reported. The epithelium remains normal to the surface or focally ulcerative tumor may overlap. Normal epithelium overlying the tumor strongly supports the diagnosis of urachal carcinoma. However, the destruction of this layer by the tumor can make the distinction between adenocarcinoma of the urachus and urachal bladder difficult. The presence of cystic glandular cystitis or cystitis transition to malignancy favors the diagnosis of adenocarcinoma of the bladder proper, as opposed to that of urachal origin.

To be continue.....

Carcinoma is Uncommon Cancer Of The Bladder

Predominantly squamous cell carcinoma of the bladder is most commonly found in the environment of schistosomiasis in the Middle East, a context that is outside the scope of this chapter.

In the western, central squamous differentiation are commonly found in patients with invasive, non-papillary TCC. As is the case with focal glandular differentiation, we know you do not have clinical significance of this finding. By contrast, pure squamous cell carcinomas are rare, and show a very particular clinical expression. The most common scenario for (non-schistosomiasis) is that the chronic irritation squamous cell cancer, usually either urolithiasis (particularly staghorn calculi) or chronic catheters in patients with paraplegia and neurogenic bladder diseases such as MS. It is typical to see keratinizing squamous metaplasia, dysplasia often in areas adjacent to these cancers.

Surgery is the mainstay of therapy for squamous cell cancer. Local control is often a bigger problem than the progression from a distance, marked difference to the situation with conventional TCC. The sensitivity to chemotherapy is universally reported to be lower for the conventional squamous cell cancer of the CTP, which further reinforces the importance of primary surgical management. Unfortunately, when these cancers are recurrent or metastatic chemotherapy expectations are limited. However, there are certainly patients have excellent responses, and there is therefore difficult to assess the risk-benefit of a trial of chemotherapy. In our limited experience, we find the combination of gemcitabine (900mgm-2 for 90 minutes), cisplatin (50mgm-2), and ifosfamide (1000mgm-2) given every 14 days to be the most attractive pattern no a clinical trial.

Interestingly, lung metastases of carcinoma of the bladder tend to cavitation, the behavior is not typical of other histologies. Our experience in trying to administer chemotherapy in the special context of patients with paraplegia (or other diseases causing neurogenic bladder) is uniformly unsatisfactory, and we can not support the use of conventional treatments such as MVAC in this context.

Small cell carcinoma

As the spindle morphology, reminiscent of the histologic features of neuroendocrine carcinomas are commonly found in patients with high grade TCC, especially as it evolves over time. At present, there is no exact consensus on diagnostic criteria for declaring a "small cell" or a subset of "neuroendocrine". Some authorities put more emphasis on the histomorphology and others in the expression of neuroendocrine markers. In the MD Anderson Cancer Center, has been our understanding that the morphology is more predictive of clinical outcome of a particular pattern of immunohistochemical markers, and so still prefer the term "small cell carcinoma" and do not require immunohistochemistry "confirmation" to apply the term. As can be deduced from clinical observation, LOH studies of the coexistence of small and TCC cells suggest descent from a common precursor, as has been shown that sarcomatoid carcinoma. In part because of the lack of well defined diagnostic criteria, incidence of small cell carcinoma is very difficult to estimate. To record the MD Anderson (which obviously reflects the referral bias), we find small cell carcinoma has an incidence of 3% (115 of 3833). Other researchers have suggested 0.5 to 0.7%.

One occasionally encounters patients with small cell carcinoma found in the prostate and it is unclear whether this is interpreted as prostate or urothelial origin. In general, there is no urothelial dysplasia in the prostatic urethra (in favor of a urothelial origin), or signs of dysplasia in the prostatic acini (in favor of a prostatic origin.)Indeed, the distinction hardly matters, as the cornerstone of therapy for either primary site is the early exposure to systemic chemotherapy (eg, etoposide and cisplatin) followed by local concentration (which would be radical surgery in our center).

As is well established for other sites, small cell carcinoma of the urothelium is an aggressive cancer characterized by early development of micrometastases, a high incidence of liver disease, and significantly, for the brain as a "sanctuary" site metastasis. The rapid growth within the bladder is also typical. Indeed, it is not uncommon for patients with large tumors that had been "completely excised" only 2 to 3 weeks earlier. This may be the basis of the relatively poor results (detailed below) with the surgical treatment of this variant.

Once a small cell component has been identified, it is important to free up a little rehearsal studios. Even for patients with minimal invasion into the bladder, the possibility of metastasis is important, and therefore all patients should have a computed tomography (CT) scan of abdomen and pelvis in search of lymph node and liver. It is also very important to maintain surveillance for the development of brain metastases at any point in the clinical course of the disease. As more effective systemic therapy is available, the issue of prophylactic cranial irradiation (as is done for some patients with small cell carcinoma of the lung) will probably have to be studied. We have recently seen two patients treated with neoadjuvant chemotherapy and surgery who later succumbed to brain metastases without any evidence of other sites of involvement. It has long been recognized that cystectomy, in this context is associated with a cure rate much lower than obtained with conventional TCC. , existing clinic has been the rule, with a maximum of 76% of patients with small cell tumors metastatic to cystectomy.

In a recent study by MD Anderson Cancer Center in experience found that pathological stage was higher than expected in 56% of patients treated with initial cystectomy. Furthermore, 20% of patients in whom cystectomy is planned initial found that surgically unresectable during surgery, despite an average of 24 days from diagnosis to surgery. In light of this experience, many institutions have reported the addition of multimodal systemic therapy approaches with radiation and / or surgery. In a review of the literature since 1995, Abbas said that the best disease-free survival was observed when cystectomy was followed by adjuvant chemotherapy with a median survival of 21.1 months.

Of the 19 patients studied by Grignon, 12 four of the five survivors were treated with adjuvant chemotherapy after cystectomy. The University of Southern California-Norris Cancer Center reported an improvement in overall survival and relapse free for patients receiving multimodal therapy, most of whom received adjuvant chemotherapy.

However, the median survival in these patients was only 13 months with a 5-year survival of 10%. Initial chemotherapy (ie, neoadjuvant systemic therapy) has also been investigated, and with more promising results. Walther reported that five of the seven patients were alive and free of the disease in more than 36 months after combined modality treatment, and indeed, the five who were alive were treated with preoperative chemotherapy. A retrospective analysis of our own experience10 in 46 patients, who were the two candidates for surgery and had potentially resectable disease, found a statistically improved survival of patients treated with preoperative chemotherapy. Patients treated with initial cystectomy had median cancer-specific survival (CSS) of 23 months, and 36% CSS at 5 years (see Figure 2). By contrast, for those treated with preoperative chemotherapy median CSS has not been reached, and 5 years was 78% of CSS. There were only four cancer-related deaths among 21 patients treated with initial chemotherapy, and none in the subset, a lower stage "for pT2N0M0 or less. It is interesting note that 7 of 25 patients treated with initial cystectomy received adjuvant chemotherapy, however, survival was no better than those treated with cystectomy alone. Given these results, the view that all patients with small cell component should be treated first (and promptly), with three or four cycles of chemotherapy incorporating etoposide and cisplatin. After chemotherapy, we favor surgical consolidation. This is based on observations that most of these patients have generalized dysplasia often show glandular elements after chemotherapy. Therefore, we can infer that a significant fraction of patients do not have a good long-term control in the bladder through the radio-therapy. Limited data from case series suggest that this radiation is indeed the case.

Unfortunately, given the rapid progression and metastatic potential of bladder cancer early small cells, many patients have surgically unresectable or metastatic disease at presentation. The most common sites are lymph nodes, liver, bone, lung and brain. With chemotherapy, the median survival ranges from 7.5 months to 15 months. There are few long-term survivors, but about 20% are alive at 3 years, which is more than 2 years longer than untreated natural history of disease. Despite the disappointing outcome in the long term, small cell urothelial tumors are highly sensitive to systemic chemotherapy, and most patients experience marked objective response is associated with rewarding (albeit temporary) palliation of symptoms

Sarcomatoid Carcinoma

The clinical course of advanced urothelial cancer is generally characterized by a more aggressive biological behavior over time. This is typically accompanied by phenotypic evolution patterns is readily recognized to reflect the more aggressive biological behavior. In this context, recognition of areas with spindled histomorphology is fairly common. When this pattern becomes dominant, cancers are often described as sarcomatoid carcinomas. These cases have long recognized, and many series of cases and fixes are available.

There remain several reports of sporadic cases each year. Almost always, recognizable as Highgrade nonspindled TCC areas are also present, suggesting that this pattern of results of evolution from a common ancestor. Indeed, by immunohistochemistry, the spindle areas are generally positive for keratin, epithelial membrane antigen and vimentin. (When the epithelial markers are lost in a significant fraction of tumor cells, the term carcinosarcoma is adequate, but the literature makes no systematic distinction between these two terms.) Clonality analysis based on loss of heterozygosity (LOH) of microsatellite markers5, 6 provides strong evidence that despite the various components can and should evolve independently once they diverge, they do, in fact, derive from a common precursor.

While it is clear that we can define a subset of sarcomatoid appearance, which is more important to know what such an important biological morphology portends. Although there appear to be particular risk factors or clinically distinctive features at initial presentation, a recurrent theme in the clinical experience with sarcomatoid urothelial cancer is having an aggressive natural history and poor outcome in relation to the classics of TCC . This is confirmed by the registration of MD Anderson in both locally advanced and metastatic settings. In view of this, we believe that the presence of a sarcomatoid component in bladder cancer minimally invasive otherwise be a strong indicator of early cystectomy. We know of no data to recommend a specific therapeutic approach of systemic therapy. Although we have investigated more intensive chemotherapy in this subgroup, who have no sense that this is justified by better results and does not endorse this approach in the absence of a clinical trial. It is very important to realize that not everything that appears spindle is dangerous.

In particular, the post-resection of sarcomatous nodules and inflammatory pseudotumor should not be confused with aggressive cancers that have some resemblance. In addition to the clinical context, it is reported that the presence of necrosis at the interface of muscle and nuclear atypia are the most useful features that distinguish true sarcomas or sarcomatoid carcinomas of these benign conditions. Although extremely rare, true sarcomas without an epithelial component occur in the bladder, and listed in the section of "sarcoma".