Management of the pancreatic metastases from renal cell carcinoma: report of four resected cases

The pancreas is an uncommon site for metastasis from renal cell carcinoma. In most cases, pancreatic metastases occur as part of widespread nodal and visceral involvement, and there is thus evidence of metastatic disease elsewhere in the body. We present 4 cases with resectable pancreatic metastases arising from renal cell tumors without involvement of the regional lymph nodes at the operation. Three cases out of 4 were asymptomatic and the pancreatic metastases were detected by routine follow-up examination of renal cell carcinoma. Aggressive surgical treatment for the solitary metastatic lesion is advocated. Spread of renal cell carcinoma to the pancreas is, however, via the hematogenous route, and even solitary pancreatic metastasis may be one of the manifestations of the systemic metastasis of renal cell carcinoma. No pancreatic regional lymph nodes metastases were noted. Pancreatectomy should be undertaken to remove the tumor with adequate resection margins while preserving as much of the gland as possible. The prognosis of pancreatic metastases arising from a renal cell carcinoma is discussed with a review of the literature. Adjuvant chemo- and endocrine therapy should also be considered in these cases.     

Clinical and pathological features of thoracic neoplasia in the horse

Thirty-eight horses with confirmed thoracic neoplasia included 28 (37.7%) with lymphosarcoma, 4 (10.5%) with metastatic renal cell carcinoma, 2 (5.3%) with primary lung carcinoma, 2 (5.3%) with secondary squamous cell carcinoma from the stomach, 1 (2.6%) with pleural mesothelioma, and 1 (2.6%) with malignant melanoma. The major clinical features included weight loss, inappetence, dyspnoea and coughing, but in cases of lung metastases, they related more to the primary site of tumour formation. Haematological and serum biochemical abnormalities were non-specific. Specific pre-mortem diagnosis was made in 14 horses; this was most readily achieved when exfoliated neoplastic cells were present in pleural fluid.     

The so-called malignant pleural effusion: a new review of direct data obtained with diagnostic pleuroscopy

We analyze a series of 896 thoracoscopies for pleural effusion, of which 78% (662/896) were due to pleural carcinomatosis, primary or metastatic. Pleural malignancy was observed mainly, in the right hemithorax (65%), arising from tumors within the diaphragm. The likelihood of finding pleural metastasis in lung cancer was 77%. When the pleural effusion is slight (less than 500 ml) the likelihood falls to 22%. We therefore advise thoracoscopy in the former and thoracotomy in the latter. Blood-stained effusion continues to have the worst prognosis (84% stemming from metastasis) and signifies an advanced stage of pleural metastasis. The pleura parietal is involved in 69% of pleural carcinomatosis cases, and in 80% when the lower hemithorax or the area around breast or lung tumors are involved. The cytology yield was 45.9%, though always depending on extent of metastasis. When metastasis was slight, the likelihood of positive cytology was less (19%) and when metastasis was generalized throughout the entire pleura the likelihood increased to 73%. We found no reason to think that the cells in most pleural liquids are able to nest and form tumoral niches. The origin of such cell nests was rather found to be in shedding from the metastases themselves, from lung tumors or from carcinomatous lymphangitis by lymphatic obstruction. The diagnostic yield of thoracoscopy once again proved to be superior to that of pleural biopsy.     

Carcinosarcoma of the adult kidney

Carcinosarcoma of the adult kidney is a very rare tumour and there are only a few well documented cases in the literature. In this report such a tumour is described from a 50-year-old white male, which progressed very rapidly with widespread metastases. Histologically, the tumour consisted of renal cell carcinoma and fibrosarcomatous components. The interesting features in this case were that both the carcinomatous and sarcomatous elements of the tumour exhibited metastases separately to various organs.     

Metastatic RCC arising in a transplant kidney

We report a case of metastatic renal cell carcinoma arising in a cadaver transplant kidney 6 years after transplantation. Due to molecular analysis of the tumor tissue we could prove that the carcinoma originated from the male donor. After tumor resection and interruption of immunotherapy, the concomitant bone and lymph node metastases resolved with alpha-interferon and interleukin-2-based immunotherapy.     

Lymphatogenous spread of renal cell carcinoma: an autopsy study

PURPOSE: We investigated the occurrence and extent of metastatic spread, especially regarding lymph nodes, of renal cell carcinoma. MATERIALS AND METHODS: From 1958 to 1982, 554 cases of renal cell carcinoma were diagnosed at autopsy. Clinical data and autopsy findings were reevaluated, and the occurrence of lymph node metastases was analyzed by histological examination of retroperitoneal, mediastinal, supraclavicular, axillary and inguinal lymph nodes. RESULTS: Distant metastases were revealed in 119 cases (21.5%), including 31 (5.6%) with single metastases. In 88 cases (16%) renal cancer was the cause of death. Lymphatogenous dissemination was detected in 80 cases of which 75 had additional, mostly multifocal metastatic spread. Consequently lymph node metastases restricted to the paracaval and/or para-aortic lymph nodes were noted in only 5 cases (0.9%). CONCLUSIONS: Of the 554 cases of clinically unrecognized renal cell carcinoma almost all with lymphatic spread had additional distant metastases. Therefore, the therapeutic effect of extensive retroperitoneal lymph node dissection in association with radical nephrectomy seems to be low. However, more limited lymph node dissection may be useful, mainly as a staging procedure.     

CT characteristics of metastatic disease of the pancreas

Contrast material-enhanced computed tomographic (CT) scans obtained over a 10-year period in 66 patients with metastases to the pancreas were retrospectively reviewed. The primary tumors most commonly responsible for these metastases were renal cell carcinoma (30.3%) and bronchogenic carcinoma (22.7%). Metastases showed no predilection for any particular part of the pancreas. The majority (75.8%) of metastases appeared as tumors with discrete margins, and most of these tumors were round or ovoid with smooth borders. Over three-fourths of the lesions demonstrated enhancement (usually heterogeneous). Vascular involvement was uncommon. In those patients in whom pancreatic metastases were discovered some time after the primary tumor was identified, the interval ranged from 2 to 295 months, with the longest mean interval (120.2 months) being associated with metastatic tumors from renal cell carcinoma. The appearance of these tumors at CT--predominantly hyperattenuating masses, often with nonenhancing internal components--was similar to that of primary renal cell carcinoma. In most pancreatic metastases, however, clinical information in conjunction with CT characteristics such as multiplicity of tumors or hypervascularity permit differentiation of metastases from primary neoplasm. When diagnosis of a pancreatic neoplasm is uncertain, percutaneous biopsy often permits histologic confirmation of the tumor type.     

Pulmonary infarcts can mimic pulmonary metastases from renal cancer

PURPOSE: Spontaneous regression of pulmonary metastases from renal cell carcinoma is a rare but well documented event. We present 2 recent cases that were radiographically consistent with pulmonary metastases from renal cell carcinoma but were pathologically shown to be pulmonary infarcts with no evidence of metastatic cells. Stable pulmonary infarcts can be misconstrued as metastatic disease in patients with renal cell carcinoma while resolving pulmonary infarcts may represent a subpopulation of patients with apparent spontaneous regression. Clinical implications of these findings are discussed. MATERIALS AND METHODS: Clinical and pathological data from 2 patients with large primary renal tumors, venous thrombi and lung masses were reviewed. Data from these cases, as well as pertinent urological and pathological literature, are presented. RESULTS: Although preoperative assessment was consistent with stage IV renal cell carcinoma, pathological examination of the lung masses in these patients showed no evidence of tumor cells. CONCLUSIONS: Pulmonary infarcts may mimic resolving or stable pulmonary metastasis in patients with renal cell carcinoma. Accurate clinical staging is crucial for the prognosis and treatment of renal cell carcinoma. Mistaking pulmonary infarcts for metastatic lesions can lead to inaccurate prognoses and inappropriate treatment.     

Late metastasis in thyroid gland after nephrectomy for renal clear cell carcinoma

Renal carcinoma natural history is unpredictable. Spontaneous metastases regression after nephrectomy, as well as late recurrence are suggestive of this peculiar human neoplasm. tumor metastases localized to thyroid gland are uncommon in clinical practice; and carcinoma of the kidney, breast, lung, melanoma and gastrointestinal tract tumors are responsible for the majority of them. This paper reports on a patient with metachronous thyroid gland metastases after fourteen years of renal carcinoma nephrectomy, with one year after hemithyroidectomy recurrence on cervical striated muscle followed by surgical excision. Therapeutical aspects are briefly reviewed in literature, emphasizing surgical treatment and the need of all-life follow-up, with more alert attitude toward thyroid gland after renal cell carcinoma nephrectomy.     

Cervical lymph node metastasis disclosing a Grawitz's tumor. Apropos of a case

The authors report a case of advanced renal cell carcinoma presenting in the form of cervical lymph node metastases. In the absence of any specific clinical signs and an ENT portal of entry, this obviously neoplastic subdigastric lymphadenopathy was apparently primary. Histopathological examination of the cervical lymph node dissection revealed metastatic renal cell carcinoma and complementary investigations revealed the primary tumour in the right kidney. The course was fatal within several weeks despite treatment. The various problems raised by this truly metastatic disease are discussed.     

Operative strategy in patients with MRI-identified dual pathology and temporal lobe epilepsy

The liver is the most common site of hematogenous metastases from colorectal carcinoma. Kupffer cells (KC), which line the hepatic sinusoids, may form the first line of defense against circulating tumor cells. The purpose of this study was to determine the effect of hepatic metastases and intra-abdominal tumor growth on KC binding of human colorectal carcinoma (HCRC) cells. MIP-101, a poorly metastatic cell line, and CX-1, a highly metastatic cell line, were injected intrasplenically into nude mice and KC were isolated by collagenase perfusion at varying intervals after injection. Conditioned media were collected from MIP-101, CCL 188 and CX-1 to determine their in vitro effect on KC function. KC from MIP-101 injected mice (14% liver metastases, 100% splenic tumors) bound a significantly greater number of MIP-101 and clone A cells than CX-1 cells in vitro. KC isolated from mice 5 weeks after CX-1 injection (100% liver metastases) also showed increased binding of MIP-101 and clone A cells compared to CX-1 cells. Similar results were obtained when tumor cell binding to normal human liver KC was compared to binding to KC from human livers from patients with hepatic metastasis from colorectal cancer. In contrast KC obtained from mice 3 weeks after CX-1 injection (44% liver metastases) showed significantly decreased binding of MIP-101 and clone A cells. The conditioned medium from CX-1 cells significantly decreased the in vitro binding of both MIP-101 and CX-1 by KC. These results indicate that the ability of KC to bind HCRC cells (which precedes phagocytosis and tumor cell killing) is a dynamic function and affected by concomitant tumor growth. HCRC cells may alter KC function via the production of specific tumor-derived soluble factors. In order to devise new and more effective therapeutic options in the treatment of liver metastases the nature of this tumor cell-KC interaction must be better understood.     

CT diagnosis and differential diagnosis of renal spaca occupying lesions (author's transl)

In 76 patients with space occupying lesions of the kidneys CT scans were performed. Size, shape and localisation of the kidneys could well be demonstrated by this method. Space occupying lesions were clearly seen, and solid tumors could be differentiated from cysts. However differential diagnosis between either primary renal cell carcinoma and metastases or between malignant and benign mass lesions was not possible. There was no problem in the diagnosis of hydronephrosis where as a differentiation between inflammatory changes and solid masses proved to be difficult. CT scanning seems to be usefull in the diagnosis of renal space occupying lesions. As a non invavise method it should be performed previous to renal angiography, which thereby becomes unnecessary in many cases.     

Metastases to the pancreas and their surgical extirpation

BACKGROUND: The pancreas is an unusual but occasionally favored site for metastases, notably from carcinomas of the kidney and lung. The pancreas may be the only identified locus of spread, and therefore may provide an opportunity for significant palliation or even cure using pancreatectomy. OBJECTIVE: To report the treatment and outcome of patients presenting with metastases to the pancreas. DESIGN: Five-year survey. SETTING: Tertiary referral center. PATIENTS: Ten patients with apparently isolated metastases to the pancreas were identified from January 1, 1991, to December 31, 1995. All patients were followed up until death or to September 1997. RESULTS: The patients had been treated previously for carcinoma of the lung (n=4), renal cell carcinoma (n=2), sarcoma (n=2), breast carcinoma (n=1), and endometrial carcinoma (n=1). The interval between primary treatment and presentation of the metastases averaged 70 months (14-24 months for lung cancer, 10 and 22 years for renal cell carcinoma, 4 and 6 years for sarcoma, 8 years for breast cancer, and 36 months for endometrial carcinoma). Metastases were initially misdiagnosed as primary pancreatic cancers in 7 patients. In 4 patients (those with renal cell cancer and sarcomas), the tumor was completely resected using total pancreatectomy (n=3) or Whipple resection (n=1). Survival after diagnosis averaged 22 months. Two of the 4 patients undergoing pancreatic resection remain alive and well 20 and 25 months after pancreatectomy. CONCLUSIONS: The pancreas may be the presenting and perhaps sole locus for metastasis, typically years after treatment for certain extrapancreatic malignant neoplasms. Recognition and surgical treatment can provide worthwhile palliation and long-term survival.     

Fluorotyping of HLA-A by sequence-specific priming and fluorogenic probing

AIMS: To determine the value of immunocytochemistry in differentiation of malignant pleural mesothelioma from carcinoma in a pleural biopsy using commercially available monoclonal antibodies. METHODS AND RESULTS: A panel of monoclonal antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen Ber-EP4, carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), Leu-M1, CD30 (Ber-H2), vimentin and desmin, was applied to 40 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic to the pleura (16 pulmonary and seven extrapulmonary). Positivities for Ber-EP4, CEA, B72.3 and Leu-M1 were found to have the highest nosologic sensitivities (87.0%, 65.2%, 52.5% and 43.5%, respectively) and specificities (97.5%, 97.5%, 100% and 95%, respectively) for carcinoma. Positive staining for vimentin had the highest sensitivity (87.5%) with 95.7% specificity for mesothelioma. Positive staining for desmin was found in 45% of mesotheliomas and 0% of carcinomas. Diagnostic sensitivity and diagnostic specificity (P-values) were calculated for these markers. In respect to the diagnostic power defined by the clinically relevant predictive values of positive and negative tests, we found that a two-marker panel of antibodies including vimentin and Ber-EP4 is most useful for the histopathological distinction between carcinoma (pulmonary or extrapulmonary) and malignant pleural mesothelioma. CONCLUSIONS: A combination of Ber-EP4 and vimentin provides the most sensitive and specific pair of markers for distinguishing between malignant pleural mesothelioma and carcinoma metastatic to the pleura. The prevalence of the tested tumours should be taken into account when evaluating the clinical value of ancillary techniques in pathology.     

Expression of structure-specific recognition protein mRNA in fetal kidney and Fe-nitrilotriacetate-induced renal carcinoma in the rat

Specific expression of the structure-specific recognition protein (SSRP) gene was investigated in rat fetal, adult, and tumor tissues using a 2.0-kb partial sequence of rat SSRP cDNA isolated from a cDNA library of rat renal cell carcinoma. The results revealed that it was rather specifically expressed in rat fetal kidney and renal cell carcinoma induced by Fenitrilotriacetate, but not in adult kidney, when various organs were tested by Northern blot analysis. In situ hybridization further demonstrated that it was located in the neoplastic cells of renal cell carcinoma and in the epithelial cells of fetal kidney but undetectable in any cells of normal adult kidney. These observations seem to imply the involvement of SSRP gene, which is believed to recognize structural alterations of DNA, in kidney development and carcinogenesis of certain types of kidney cancer.     

Expression of the plasminogen activation system in kidney cancer correlates with its aggressive phenotype

Malignant tumors contrast with benign ones in their ability to invade adjacent tissue and to metastasize. The urokinase plasminogen activator is a proteolytic enzyme that can facilitate these processes. In many carcinomas, the concentration of the urokinase plasminogen activator system is high. The high expression of these enzymes is related to tumor grade. In this study, we have investigated whether secretion of the urokinase plasminogen activator, urokinase plasminogen activator receptor, and plasminogen activator inhibitor 1 in normal kidney tissue and kidney cancer tissue follows this pattern. We have found that urokinase plasminogen activator, urokinase plasminogen activator receptor, and plasminogen activator inhibitor 1 were expressed in higher levels in kidney cancers (squamous cell carcinoma and renal cell carcinoma) than in normal kidney tissue and that these differences were statistically significant (P < or = 0.05). In renal cell carcinomas, we have observed differences between normal kidney tissue and renal cell carcinomas in males and Caucasians but not in females and African Americans (P < or = 0.05). Expression of the urokinase plasminogen activator system was also higher in grade III tumors when compared with lower-grade tumors or normal tissue.     

Effects of flutamide on pituitary and adrenal responsiveness to corticotrophin releasing factor (CRF)

Although most studies have indicated that Ber-EP4 immunostaining can assist in differentiating epithelial pleural mesotheliomas from adenocarcinomas that metastasize to the pleura, the percentage of positive cases has varied greatly among different studies. Authors of a recent publication concluded that Ber-EP4 has no diagnostic utility in separating these conditions. To determine whether Ber-EP4 has any value in distinguishing mesothelioma from adenocarcinoma, 70 formalin-fixed epithelial pleural mesotheliomas, 20 pulmonary adenocarcinomas, 59 nonpulmonary adenocarcinomas, 4 squamous cell carcinomas of the lung, 6 transitional cell carcinomas, and 31 adenocarcinomas of unknown origin that metastasized to the pleura were stained with this antibody. Reactivity was observed in 18 (26%) of 70 mesotheliomas and in all 20 (100%) of the pulmonary adenocarcinomas, in 55 (93%) of the 59 nonpulmonary adenocarcinomas, in 4 (100%) of 4 squamous cell carcinomas of the lung, in 4 (67%) of 6 transitional cell carcinomas, and in 26 (84%) of 31 adenocarcinomas of unknown origin that metastasized to the pleura. The staining in the mesotheliomas was focal and restricted to a limited number of cells, in contrast with staining in the pulmonary adenocarcinomas in which it was invariably diffuse. The extent of the staining in the nonpulmonary adenocarcinomas and the metastatic adenocarcinomas of unknown origin was less consistent--negative or focal in some cases and diffuse in others. Therefore, while Ber-EP4 seems to be helpful in separating epithelial pleural mesotheliomas from lung adenocarcinomas, its value in distinguishing mesotheliomas from other tumors metastatic to the pleura is more limited and depends largely on the site of origin of the metastatic tumor.     

Correlation of cytologic and pathohistologic findings in ultrasonically-guided thin-needle biopsy of abdominal and retroperitoneal organs

A 71-year-old woman with loss of appetite was referred to our hospital. Imaging diagnosis revealed a large, cystically dilated left kidney with a solid tumor inside the cavity and right hydronephrosis. A chest X-ray revealed multiple metastatic lesions. A horseshoe kidney was found intraoperatively and left nephroureterectomy with partial cystectomy was performed. Histological diagnosis was poorly differentiated transitional cell carcinoma. She died of progressive pulmonary metastases 2 weeks after operation. This is the 19th case of a renal pelvic tumor associated with a horseshoe kidney reported in the Japanese literature. The diagnosis was confounded by the extreme dilation and deformity of the hydronephrotic kidney.     

Disseminated infection due to Chrysosporium zonatum in a patient with chronic granulomatous disease and review of non-Aspergillus fungal infections in patients with this disease

BACKGROUND: Insulin-like growth factor-2 (IGF-2) is considered one of the autocrine growth factors in colorectal carcinoma. In addition, it is well known that IGF-2 is produced in the liver. However, the role of IGF-2 in liver metastasis is not yet understood clearly. METHODS: Immunohistochemical staining of IGF-2 and IGF-1 receptor (IGF-1R) was performed on tissue samples of liver metastases from 30 colorectal carcinoma patients. In situ hybridization of IGF-2 also was conducted on the same tissue samples. Furthermore, proliferating cell nuclear antigen (PCNA) was immunohistochemically stained for use as an indicator of the proliferative activity of cancer cells. RESULTS: Invasive margins of liver metastases were stained highly by both IGF-2 (70%) and IGF-1R (83%). Overexpression of IGF-2 protein and mRNA was observed in the normal liver adjacent to the tumor. The PCNA labeling indices (LIs) of the IGF-2 positive groups were significantly higher than those of the IGF-2 negative group (P < 0.0001). In addition, the PCNA LIs for the IGF-1R positive groups also were significantly higher than those for the IGF-1R negative group (P=0.0002). CONCLUSIONS: These findings suggest that hepatocyte-derived IGF-2 stimulates tumor cell proliferation by a paracrine mechanism and plays an important role in tumor progression in colorectal carcinoma patients with liver metastases.     

Renal cell carcinoma--a current review

Renal Cell Carcinoma is the third most common malignoma in urology. Only little is known about the etiology and risk factors; the age peak lies at 60 and twice as many men than women are affected. The clinical picture presents with a wide spectrum. Over one third of all tumours are detected accidentally by ultrasound or computed tomography in asymptomatic patients. Most common symptoms are hematuria and flank pain, the classical trials including in addition a palpable mass is rare and by mo means an early symptom. Paraneoplastic syndromes include unspecific (increased blood sedimentation rate, weight loss, fever) and endocrine symptoms (hypertension, polyglobulia, hypercalcemia). Diagnosis is based on imaging procedures. By means of sonography renal cysts may be separated from solid, space-occupying tumors. For the latter CT plays a decisive role for staging, therapeutic planning and prognosis. Further radiologic investigations (angiography, MRI) are indicated only in special situations. Rarely a biopsy is necessary for the distinction between renal cell carcinoma and metastases of other primary tumors. The only curative treatment of localized carcinoma is radical nephrectomy. Partial resection is indicated in cases of a single kidney, bilateral tumors and possibly also for tumors smaller than 4 cm in diameter. Radiotherapy is only initiated for palliation of painful skeletal metastases. In case of distant metastases--mainly pulmonary--nephrectomy should only be performed if systemic treatment is planned or if local complaints (pain, hematuria leading to anemia) exist. Chemotherapeutic drugs have no influence on survival. The effect of gestagens on life quality is questionable. Adoptive immunotherapy with cytokines (Interferon-alpha, interleukin-2) appears most promising. These substances, however, not yet been introduced into routine therapy should only be used in prospective studies. Furthermore, renal cell carcinoma is a potential candidate for gene therapy. After tumor nephrectomy follow-up investigations should be performed twice a year, because of the possibility of curative surgical treatment of late solid metastases. Prognosis of tumors restricted to the organ is good. Five year survival after operation is about 90%. However, is distant metastases exist already at the time of diagnosis 5 year survival drops to less than 10%.