Synchronous colorectal and renal carcinomas. Is it a definite clinical entity?

The aim of the study was to assess the frequency of synchronous colorectal and renal cancers among our patients. To this end we reviewed 781 consecutive patients operated on for colorectal carcinoma in our institution. Three patients (0.4%) had diagnosis of synchronous renal-cell cancer during the work-up for their colorectal primary tumours. The colon and rectum are frequently affected by multiple malignant tumours. Second primaries are not frequently associated with colorectal cancer. On the other hand, renal cell carcinoma has been described as being associated with other synchronous malignancies in up to 27.4% of cases. A recent report has described a 4.8% incidence of synchronous colorectal and renal carcinomas, which is much higher than that previously reported in the literature (0.03-0.5%). We found a 0.4% incidence of simultaneous colorectal cancer and renal cell carcinoma. The latter was invariably asymptomatic and diagnosed during the work-up for the colorectal cancer. We are unable to confirm the observation of a higher than expected incidence of synchronous colorectal and renal neoplasms. Nevertheless, the surgeon should be conscious of this association, when considering renal lesions detected during the work-up for colorectal cancer.     

The changing natural history of renal cell carcinoma

PURPOSE: Our understanding of the natural history of renal cell carcinoma, the role of nephrectomy, the benefits of immunotherapy and the possibilities of new technologies are evolving and being integrated with advances in classification and staging. We reviewed the relevant literature to clarify these pertinent questions and provide a current review of the changes in the epidemiology, treatment and prognosis of patients with renal cell carcinoma. MATERIALS AND METHODS: We comprehensively reviewed the peer reviewed literature on the current management of and results of treatment for renal cell carcinoma. RESULTS: The incidence of and mortality from renal cell carcinoma have continuously increased during the last 50 years. Despite this increase in the number of new patients and consequently the number of deaths yearly the percent of those surviving for 5 years has notably improved. Factors related to improved survival include advances in renal imaging, earlier diagnosis, improved staging, better understanding of prognostic indicators, refinement in surgical technique and the introduction of immunotherapy approaches for advanced disease. CONCLUSIONS: Currently patients with localized and metastatic renal cell carcinoma have had improvements in outlook and the therapeutic options available have expanded.     

The effect of bilaterality,pathological features and surgical outcome in nonhereditary renal cell carcinoma

PURPOSE: We evaluated the differences in cancer specific, distant metastasis-free and local recurrence-free survival in patients with sporadic subtype concordant bilateral synchronous renal cell carcinoma and those with unilateral renal cell carcinoma, controlling for the covariates of subtype, stage, tumor size, grade and necrosis. We also analyzed early surgical complications and long-term renal function in patients who underwent staged surgery and those who underwent a single operation for bilateral synchronous renal cell carcinoma. MATERIALS AND METHODS: We retrospectively evaluated 44 patients with sporadic subtype concordant bilateral synchronous renal cell carcinoma treated at our institution between 1970 and 1998. There were 32 patients with bilateral synchronous clear cell renal cell carcinoma and 12 with bilateral synchronous papillary renal cell carcinoma. These patients were compared with 1,714 with sporadic unilateral clear cell renal cell carcinoma and 322 with sporadic unilateral papillary renal cell carcinoma treated with partial or radical nephrectomy during that period. Outcomes were estimated using the Kaplan-Meier method and Cox proportional hazard models were used to test associations with outcome. RESULTS: Clinicopathological features were similar for patients with bilateral synchronous and unilateral renal cell carcinoma except for the incidence of multifocality, which was 28% and 33% for bilateral synchronous clear cell and papillary renal cell carcinoma compared with 2% and 7% for unilateral clear cell and papillary renal cell carcinoma, respectively. Cancer specific survival and distant metastasis-free survival in patients with bilateral synchronous disease was similar to that in those with unilateral disease when controlling for subtype, stage, tumor size, grade and tumor necrosis. However, patients with bilateral synchronous clear cell renal cell carcinoma were more likely to experience local recurrence even after controlling for these covariates. The majority of patients (84%) with bilateral synchronous disease underwent bilateral surgery at a single operation. The incidence of early surgical complications was low, in that only 2 patients had urinary extravasation, 3 had acute renal failure and 1 was ultimately rendered anephric and required hemodialysis. CONCLUSIONS: The incidence of multifocality was greater in patients with bilateral synchronous renal cell carcinoma than in those with unilateral renal cell carcinoma. There were no statistically significant differences in cancer specific and distant metastasis-free survival in patients with bilateral synchronous renal cell carcinoma and unilateral renal cell carcinoma of the same histological subtype. These results suggest that subtype concordant bilateral renal cell carcinoma is a result of multiple de novo primary events rather than primary renal cell carcinoma with contralateral renal metastasis. A surgical approach is appropriate for bilateral synchronous renal cell carcinoma and most cases can be approached at a single surgical procedure with acceptable morbidity.     

Renal tumors in end‐stage renal disease: A comprehensive review

The incidence of end‐stage renal disease has increased owing to the greater prevalence of patients with chronic kidney disease and diabetes mellitus. End‐stage renal disease is usually accompanied by acquired cystic disease and is a risk factor for renal cell carcinoma. The present review discusses the etiology of renal cell carcinoma in end‐stage renal disease patients, focusing on two unique renal cell carcinoma histological subtypes: acquired cystic disease‐associated renal cell carcinoma and clear cell papillary renal cell carcinoma. Acquired cystic disease‐associated renal cell carcinoma occurs almost exclusively in patients who underwent hemodialysis, especially long‐term (>10 years) hemodialysis. Its histology is distinctive: a cribriform or sieve‐like architecture with intra‐ or intracystic lumina; tumor cells containing abundant eosinophilic cytoplasm and large nuclei with prominent nucleoli; and most notably, calcium oxalate crystal deposition. Recognition of the crystals is critical for diagnosing acquired cystic disease‐associated renal cell carcinoma. Acquired cystic disease‐associated renal cell carcinoma typically has an indolent clinical course, except in cases with sarcomatoid components. Clear cell papillary renal cell carcinoma also has an indolent course (no cases involving metastasis have been reported to date), and its features resemble those of both clear cell renal cell carcinoma and papillary renal cell carcinoma. Unlike acquired cystic disease‐associated renal cell carcinoma, which occurs only in end‐stage renal disease patients, clear cell papillary renal cell carcinoma occurs in non‐end‐stage renal disease patients as well. Additional renal tumors in end‐stage renal disease patients include anastomosing hemangiomas. Long‐term hemodialysis worsens the prognosis of end‐stage renal disease patients with renal cell carcinoma, regardless of its original histological subtype, presumably by inducing oxidative stress and sarcomatoid transformation.     

Cytoreductive nephrectomy for metastatic renal cell carcinoma with nonclear cell histology

PURPOSE: To our knowledge the benefit of cytoreductive surgery for patients with metastatic renal cell carcinoma with nonclear cell histology is unknown. In this retrospective study we report our experience with cytoreductive nephrectomy for nonclear cell metastatic renal cell carcinoma at M. D. Anderson Cancer Center. We compared the outcomes with those in patients with clear cell metastatic renal cell carcinoma. MATERIALS AND METHODS: From 1991 to 2006, 606 patients with metastatic renal cell carcinoma underwent cytoreductive nephrectomy and they formed the basis of this report. Of these patients 92 had nonclear cell metastatic renal cell carcinoma. The remaining 514 patients had clear cell metastatic renal cell carcinoma and they formed a comparative group. Multivariate Cox regression analysis was performed to evaluate the relationship between clinical variables and histology (clear cell vs nonclear cell) on disease specific survival. RESULTS: Compared with patients with clear cell histology those with nonclear cell metastatic renal cell carcinoma were younger (p = 0.0001), and more likely to have nodal metastases (p <0.0001) and sarcomatoid features (23% vs 13%, p = 0.026). On multivariate analysis median disease specific survival in patients with nonclear cell histology was significantly worse than that in patients with clear cell metastatic renal cell carcinoma (9.7 vs 20.3 months, p = 0.0003) even after adjusting for T stage, grade, performance status, age and sarcomatoid features. Sarcomatoid features were a predictor of poor outcome in cases of clear and nonclear cell histology, although even in the absence of sarcomatoid features nonclear cell histology was associated with worse disease specific survival (p = 0.017). Interestingly although there was a significantly higher incidence of positive nodes in patients with nonclear histology (p <0.0001), this phenotype was not associated with a worse disease specific survival, as it was in those with clear cell histology (p = 0.0001). In fact, patients with node negative disease with nonclear cell histology had the worst prognosis overall in the entire group. CONCLUSIONS: Patients with nonclear cell metastatic renal cell carcinoma were younger and had a higher incidence of nodal metastases, a higher incidence of sarcomatoid features and a worse prognosis than those with clear cell histology who underwent cytoreductive surgery.     

Transitional carcinoma of the ureter and ipsilateral synchronous renal cell carcinoma in hydronephrotic atrophic kidney: infrequent association

We report a new case of simultaneous occurrence of renal cell carcinoma and transitional cell carcinoma into ipsilateral ureter. A review of the literature to date indicates this is the 45 world-wide case and the 8 in the Spanish publications.     

RENAL MEDULLARY CARCINOMA

Purpose

Renal medullary carcinoma is a rare and extremely aggressive neoplasm that almost always develops in young patients with sickle cell trait. To our knowledge all cases to date have been metastatic at surgical resection. Pathological examination reveals an aggressive tumor mainly involving the renal medulla with a varied morphology. The prognosis is dismal. Mean survival from the time of resection is 15 weeks (range 2 to 52). The disease course has not been altered by surgery, radiotherapy or various regimens of chemotherapeutic agents.

Materials and Methods

We add to the literature our experience treating renal medullary carcinoma in 2 cases and review the existing literature on this disease.

Results

Both patients whom we treated died of the disease, as have the other 35 patients described in the literature.

Conclusions

A high index of suspicion may lead to earlier diagnosis and treatment, and survival of patients with renal medullary carcinoma.     

Acquired cystic disease of kidney associated with renal cell carcinoma in chronic dialysis patients.

We describe 2 cases of acquired cystic disease of the kidney (ACDK) associated with renal cell carcinoma in patients treated with long-term hemodialysis. Both patients have had dialysis for five and eight years, respectively. Renal cell carcinomas of these patients are small, averaging 2 cm in diameter. They are clear cell type. Atypical epithelial hyperplasia arising from cystic areas can be seen intermingling with carcinoma. This confirms that atypical epithelial hyperplasia is a precursor of renal cell carcinoma. Although the incidence of renal cell carcinoma arising in ACDK is on the rise, the issue of how to manage patients with ACDK remained unsettled and required further study.     

The role of arterial embolization in renal cell carcinoma.

Twenty-five years ago arterial embolization was introduced to facilitate the surgical excision of the carcinomatous kidney or to palliate symptoms, such as haemorrhage from non-resectable tumours. The role of this technique in the therapeutic armamentarium has been a source of debate in the literature. We reviewed all the available literature. A total of 389 papers were evaluated. Fifty-one publications and 3225 case histories met explicit entry criteria for inclusion. Until now no prospective randomized study of this approach to the management of renal carcinoma has been published. In the majority of studies the patients are grouped together irrespective of indication, i.e. pre-operative or palliative. Few articles are prospective or contain clear information regarding tumour stage, indication and adequate follow-up. Although we are not able to distinguish with certainty the effect of embolization on the course of the disease, it seems that complete pre-operative renal artery embolization facilitates the excision of large vein-invading tumours. The optimal delay between embolization and operation is probably one day. The embolization material of choice is ethanol. Palliative embolization in non-operable tumours with serious haemorrhage seems to have been successful in most cases. The scientific basis for the implementation of renal artery embolization in renal cell carcinoma is weak. We believe that either controlled trials or parallel prospective cohort studies should be undertaken to compare treatment of selected locally advanced renal carcinomas with and without embolization.     

Primary malignant tumours associated with renal cell carcinoma.

Of 360 patients with primary renal cell carcinoma seen at the Vancouver General Hospital between 1957 and 1976, 33 had associated primary malignant lesions. A review of the 166 patients who had ablative surgery revealed that they were four times more likely to have a synchronous primary malignant tumour than the other patients. The incidence of asynchronous primary malignant tumours was not increased. This may be related to the fact that the patients' full life charts were not available. In 18 patients dying of other causes in whom an incidental renal cell carcinoma was found, 5 (28%) died of other malignant tumours. In a comparable age group from the general population, 19% are at risk of death from malignant disease. The frequency of synchronous contralateral renal cell carcinoma in our series was 50 times greater than the frequency of primary renal cell carcinoma in a corresponding sector of the general population.     

How accurate is diagnostic imaging in determination of size and multifocality of renal cell carcinoma as a prerequisite for nephron-sparing surgery?

Background: The indication for elective nephron-sparing surgery (NSS) in renal cell carcinoma (RCC) is under discussion in the urological literature. The main problem of NSS is the multifocality of RCC. The presented study was preformed to assess the accuracy of pre-and intraoperative ultrasound (US), and computerized tomography (CT) in determination of tumor size and detection of multifocal lesions.Materials and methods: Tumor size was measured by preoperative US and CT and compared with the tumor diameters in gross sections of the neoplastic kidneys. Multifocality was determined by 3-mm step sectioning of the nephrectomy specimen, and the results were correlated with preoperative US and CT on the one hand, and the ex situ sonography of the nephrectomized kidney on the other hand.Results: US and CT show similar results in the determination of the tumor size. In only 22.9%, preoperative US and CT were able to detect multifocal tumors. Ex situ sonography had a sensitivity of 40.0% and a specificity of 87.2% in this regard.Conclusions: In preparation for nephron-sparing surgery of renal cell carcinoma, neither preoperative routine imaging, nor intraoperative ultrasound can safely predict multifocal lesions of renal cell carcinoma.CommentaryLocal tumor recurrence following nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) may be due to incomplete resection of the primary tumor, occult multicentric disease or the development of a new primary or metastatic focus of RCC in the renal remnant. The risk of multicentric disease in RCC has been evaluated and debated extensively in the literature. RCC generally occurs as a discrete focal lesion rather than an infiltrative process which is seen in carcinoma of the prostate. At issue is whether the molecular events that give rise to malignant transformation affect a discrete segment of the kidney or a broader segment of the renal tubular epithelium. A high incidence of multicentric RCC has been reported in patients with germ line mutations such as those that exist in von Hippel Lindau disease and other forms of hereditary RCC suggesting a global predisposition to malignant degeneration throughout the entire renal parenchyma.The incidence of multicentricity in sporadic RCC has been less clear. Emerging cytogenetic and molecular data suggest that satellite lesions may occasionally arise from the same malignant clone as their corresponding primary lesion and may therefore represent biologically significant intra-renal metastasises. A recent review of published studies comprising over 1100 cases of sporadic RCC indicated an aggregate incidence of 15.2% of tumor multifocality (range 6.5%–28%)[1]. It is important to remember that these studies represent a diverse group of patients and that RCC is in fact a heterogenous group of tumors. The risk of multicentricity is not equal in all patients and appears to be related to other prognostic variables such as tumor histology, stage and grade. For example, papillary RCC is known to be associated with a higher incidence of multifocality than the more common clear cell variant. The risk of multifocal disease also increases with larger tumors, particularly those that extend beyond the renal capsule (pT3+). Finally, some microfocal tumors are of unknown biological significance such as the finding of satellite adenomas. Of importance when considering relative indications for elective NSS is the incidence of multifocality when the primary or index tumor is ⩽ 4 cm. A recent review of the literature indicated that the incidence of multifocality in this setting is approximately 5%.The most worrisome implication of multifocal RCC is that this will predispose to an increased risk of local tumor recurrence following NSS. Although this potential risk must be considered, the relationship between multifocality and local recurrence is neither linear or predictable as suggested by the low overall local recurrence rates reported following NSS in several large series. In nearly 1800 cases of NSS reported in the literature to date, the risk of local tumor recurrence has ranged from 0–10% and is clearly lowest among patients undergoing elective NSS for small (⩽ 4 cm) low stage lesions [1]. The true biologic significance of multicentric renal tumors and their implication for NSS therefore remain to be fully elucidated.[1] Uzzo RG, Novick AC. Nephron-sparing surgery for renal tumors: indications, techniques and outcomes. J Urol 2001;166:6–18.Andrew C. Novick, M.D.     

Renal cell carcinoma detected in a cadaveric donor after orthotopic liver and contralateral renal transplantation in two recipients: four-year follow-up

BACKGROUND: Although rare, renal cell carcinoma has been found during renal recovery for cadaveric organ transplantation. Previously, we reported this incidence to be 0.9%. In one cadaveric donor, the liver and left kidney had been transplanted before the discovery of renal cell carcinoma (T1) in the right kidney. METHODS: We retrospectively reviewed the medical records of two patients who had received cadaveric allografts from a donor with a known renal cell carcinoma. RESULTS: Both patients have been followed for 4 years with blood chemistries and chest x-ray every 3 months for year 1, every 4 months for years 2 and 3, and every 6 months thereafter. They also underwent allograft ultrasound every 6 months and an annual CT scan of the abdomen. Both patients have shown no evidence of metastatic disease throughout their follow-up. DISCUSSION: In the rare instance that a patient receives an organ from a cadaveric donor with a known renal cell carcinoma, it is mandatory to follow these patients closely observing for both allograft recurrence and metastatic disease.     

Hereditary renal cell carcinoma: genetics,clinical features,and surgical considerations

Objectives

Hereditary renal cancer syndromes have been described and have illuminated novel methods to treat sporadic renal cell carcinoma. In this work, we aimed to review the genetic basis, molecular pathology and clinical manifestations of hereditary syndromes, as well as outline principles of surgical management and use of targeted therapy.

Methods

We performed a comprehensive review of selected peer-reviewed publications regarding hereditary renal cancer syndromes, their genetic basis, and recommendations for surgical management.

Results

The major syndromes contributing to hereditary renal cell carcinoma are discussed along with relevant literature guiding their management. The evolving surgical and molecular treatments are discussed.

Conclusions

Identification of genetic basis of hereditary carcinomas provides opportunity for targeted therapy of metastatic sporadic renal cell carcinoma.  Appropriate and timely surgical management of hereditary renal cancers decreases the possibility of development of metastatic disease, and allows for preservation of renal function despite the need for repeat surgical interventions.     

Intrascrotal metastasis of renal cell carcinoma. Case reports and review of the literature

In a series of 235 patients with testicular tumors 2 elderly patients (0.9%) had secondary testicular tumors: 1 from a renal cell carcinoma and 1 from an unclassified anaplastic neoplasm. The pathogenesis of intrascrotal metastases of renal carcinoma is demonstrated by angiography of the dilated spermatic vein. In a literature survey the incidence rate of secondary testicular tumors is found to range from 0.3 to 3.6%. 30 cases of intrascrotal secondaries of renal cell carcinoma have been identified in the literature.     

Multiloculated renal cell carcinoma

Multiloculated renal cell carcinoma and multilocular renal cyst with renal cell carcinoma are uncommon diseases. We report on 2 cases of multiloculated renal cell carcinoma. To our knowledge 16 cases of multiloculated renal cell carcinoma and multilocular renal cyst with renal cell carcinoma have been previously described in detail. The authors review the literature and discuss the aetiology and diagnosis of the disease.     

Collecting duct carcinoma of the kidney: a case report and review of the literature.

Collecting duct carcinoma of the kidney is unique and rarely reported. The histological and ultrastructural characteristics of this tumor are well described in the pathological literature. However, there are few reports documenting the clinical presentation and long-term prognosis in patients with this unusual malignancy. Collecting duct carcinoma arises from the epithelium of the collecting tubules within the medulla and secondarily invades the renal cortex. The tumor occurs in a younger age group than is typical for renal cell carcinoma and most patients appear to have metastatic disease at presentation. We describe a case of this uncommon tumor and review the literature.     

In vitro assessment of cell-mediated immunity in patients with renal cell carcinoma.

We evaluated 25 patients with renal cell carcinoma for cell-mediated immunity using the microtoxicity assay. Normal controls frequently exhibited significant cell inhibition. The mean percentage cell inhibition in patients after nephrectomy was significantly higher than in patients before nephrectomy and significantly higher than normal male subjects. No other correlation was found with respect to the stage of the disease. The incidence of significant autoblocking activity was noted more commonly in patients after nephrectomy than in patients before nephrectomy.     

Management of locally recurrent renal cell carcinoma after partial nephrectomy

While partial nephrectomy can provide effective treatment for selected patients with renal cell carcinoma, postoperative local tumor recurs in approximately 10 per cent of the cases. We describe 4 patients in whom tumor recurred in a solitary renal remnant after partial nephrectomy for renal cell carcinoma 1 to 6 years previously. The original tumor was pathological stage I in 2 patients and stage III in 2. Neither of the patients with stage I renal cell carcinoma had metastatic disease when locally recurrent carcinoma was noted. A second partial nephrectomy was done in these patients and they are alive 1 and 10 years later. Both patients with stage III renal cell carcinoma also had metastatic disease when locally recurrent carcinoma was noted. One patient died 1 year later and the other is alive 1 year later. Patients who undergo partial nephrectomy for renal cell carcinoma should be followed closely to allow for early detection of local tumor recurrence. When this occurs, secondary surgical treatment may be possible with complete tumor excision and the opportunity for extended survival.     

Unclassified renal cell carcinoma: clinical features and prognostic impact of a new histological subtype

PURPOSE: We characterized the histopathological features and clinical behavior of unclassified renal cell carcinoma and compared the prognostic outcome in patients with unclassified and conventional (clear cell) renal cell carcinoma. MATERIALS AND METHODS: A total of 31 patients with unclassified renal cell carcinoma are included in the kidney cancer database at our institution. Another 317 matched patients with clear cell carcinoma were used for comparing demographic, clinical, pathological and survival data. RESULTS: The incidence of unclassified renal cell carcinoma was 2.9%. At initial diagnosis 29 patients (94%) with unclassified and 264 (83%) with clear cell renal cell carcinoma had metastatic disease (p = 0.143). Compared with the clear cell variety unclassified disease was associated with larger tumors (p = 0.005), increased risk of adrenal gland involvement (25% of cases, p = 0.0001), direct invasion to adjacent organs (42%, p = 0.00001), bone (52%, p = 0.022), regional (52%, p = 0.0042) and nonregional lymph node (41%, p = 0.03) metastases. Nephrectomy was less likely to be attempted or completed in unclassified renal cell carcinoma cases (61%, p = 0.00007). Unclassified histology was a significant indicator for poor prognosis on multivariate analysis (p <0.0001). Median survival in patients with unclassified renal cell carcinoma was 4.3 months. Nephrectomy alone did not confer any survival advantage in these cases (p = 0.1086), while immunotherapy did (p = 0.008). The combination of nephrectomy and immunotherapy yielded improved survival over immunotherapy alone (p = 0.0356) but patients with unclassified renal cell carcinoma were significantly less likely than those with clear cell disease to be eligible for immunotherapy regimens (p = 0.05). CONCLUSIONS: Unclassified renal cell carcinoma is associated with distinct and highly aggressive biological behavior, and poor clinical outcome. Whenever feasible, immunotherapy with nephrectomy is warranted.