Successful treatment for renal cell carcinoma with lung metastases by interleukin-2 and interferon-alfa: a case report

We report a case in which a regimen of interleukin-2 (IL-2) and interferon alfa (IFN-alpha) was effective against renal cell carcinoma with lung metastases. A 69-year-old man diagnosed with right renal tumor had not received treatment for 28 months. He was admitted to our hospital for treatment. Computed tomographic (CT) findings showed a right renal tumor 11.5 cm in diameter and multiple lung metastases. Right nephrectomy was performed, and pathological examination was renal cell carcinoma (clear cell carcinoma, G2, pT3a). A regimen of IL-2 and IFN-alpha was selected as an adjuvant therapy. He received 70 x 10(4) JRU/day of IL-2 (div) 5 times a week, and 600 x 10(4) IU/day of IFN-alpha intramuscularly 3 times a week for 8 weeks. Thereafter, both treatments were continued 3 times a week. CT scan showed a complete response on lung metastases 12 months and no recurrence has been observed on CT scan for 16 months after operation.     

Synergetic responses after administration of interleukin-2 and Interferon-alpha combined with gamma knife radiosurgery in a patient with multiple lung and brain metastases: a case report

A 51-year-old man with left renal tumor and multiple lung metastases was admitted to our hospital for treatment. Left nephrectomy was performed, and pathological diagnosis was renal cell carcinoma (clear cell carcinoma, G2, pT3a). Initially, Interferon-alpha (IFN-alpha) therapy was started for lung metastases. About 40 days after surgery, head magnetic resonance imaging revealed brain metastases, and therefore gamma knife radiosurgery(GKS) was performed. Since chest computed tomography showed no change in lung metastases, we tried a combination of interleukin-2 (IL-2) and IFN-alpha therapy to elininate those metastases. As a result, neither lung nor brain metastases could be detected at the 4th month follow-up examination. At 5 months after the IL-2 and IFN-alpha therapy, the patient attempted suicide. Therefore, the IL-2 and IFN-alpha therapy was stopped and an antidepressant was prescribed. Now 11 months after withdrawal of the IL-2 and IFN-alpha, the patient's mental condition remains stable. No recurrence of the cancer has been detected by CT.     

A case of renal cell carcinoma found after skin metastasis

A case of renal cell carcinoma, found after skin metastasis is presented. A 79-year-old man visited Osaka JR hospital, complaining of a painless nodular mass on his right chest. The mass was resected and histopathological examination revealed a clear cell carcinoma (alveolar type, G1) with no involvement of the mammary gland. Abdominal ultrasound and magnetic resonance imaging revealed a heterogenous lower pole mass in the right kidney. Ultrasound-guided needle biopsy of the right renal mass was performed for histopathological diagnosis, which was clear cell carcinoma (alveolar type, G1). At that time, multiple metastases appeared in bilateral lung fields. The patient is currently receiving interferon-alpha therapy, without surgical treatment.     

A case of multiple lung metastases and cervical lymph node metastasis of renal cell carcinoma failing to respond to interferon-alpha (IFN-alpha) but markedly responding to interleukin-2 (IL-2)

A 59-year-old man was admitted to our hospital with a left renal mass. A tumor was removed by radical nephrectomy and histological examination revealed renal cell carcinoma (pT2 N0 V1a). Two years later, CT scan showed multiple lung metastases. Despite treatment with recombinant IFN-alpha 2b, 5-FU, and MMC, the disease showed slow progression. About three years after the start of combination therapy, cervical lymph node metastasis appeared. Administration of interleukin-2 (IL-2) was attempted. Intravenous IL-2 therapy was started at a low daily dose of 35 x 10(4) JRU, and the daily dose was increased to 140 x 10(4) JRU. Because of side effect, the dose was subsequently decreased to 70 x 10(4) JRU three times per week. After 31 weeks of IL-2 therapy, his multiple lung metastases and cervical lymph node metastasis disappeared. The patient's natural killer cell (NK) activity and Lymphokine activated killer cell (LAK) activity were low before IL-2 therapy, but both NK activity and LAK activity showed a marked increase after IL-2 therapy started. Therefore, the tumor response to IL-2 was suggested to depend on NK activity and LAK activity.     

Evaluation of bone metastases from renal cell carcinoma

Twenty-nine cases of bone metastases from renal cell carcinoma were examined. Eight had metastatic bone pain as the initial symptom and were diagnosed that the primary lesion was in a kidney. In eight cases bone metastases appeared after treatment of the primary site. Seven had only bone metastases and another 22 cases had multiple metastases in organs such as the lung and lymph node when the bone metastasis was found. Curable surgical treatment was performed in only 2 cases. The survival curve of these patients were: 1 year; 41 per cent, 2 year; 30 per cent and 3 year; 15 per cent. Bone scan used for detection of bone metastases of carcinoma frequently ends with false positive results. CT scan and angiography are available for differential diagnosis of bone metastasis. We examined 6 cases (9 lesions) of bone metastases from renal cell carcinoma (3 pelvic bones, 2 lumbar bones, 2 femurs and 2 humerus). All lesions were hypervascular by angiography and were easily diagnosed as bone metastases. For early detection of bone metastases from renal cell carcinoma, angiography is useful because hypervascularity and tumor stain are easily detected even in such small lesions as 2 cm. Angiography was also useful for chemoembolization.     

Long-term survival in patients with metastatic renal cell carcinoma managed with conservative therapy: a report of two cases

Case 1. A 58-year-old man underwent radical nephrectomy due to a tumor in the left kidney (renal cell carcinoma, clear cell subtype, G3, pT1bpN0) in 1988. Thirteen years later, he underwent surgical resection of metastases to lung and cerebrum and gamma ray knife resection of two other sites of metastases to cerebrum in 2001. He had no evidence of disease in April, 2003. Case 2. A 53-year-old man underwent radical nephrectomy due to a tumor in the right kidney (renal cell carcinoma, clear cell type, pT1apN0) in 1987. From 1996 to 2001, irradiation therapy to multiple metastases to thoracic vertebrae (50 Gy), rib (50 Gy), para-aorta lymph nodes (40 Gy), sacrum (44 Gy) and sternum (44 Gy), and surgical resection of dermal metastasis were performed. Paraplegia occurred due to regrowth of thoracic bone metastasis in December, 2001. In February, 2002, he died of septic shock caused by infection of decubitus. Surgical resection and palliative therapy of recurrent metastatic foci was useful to improve the quality of life and probably prognosis.     

Ureteral and bladder metastases of renal cell carcinoma following synchronous renal cell carcinoma and bladder cancer; a case report

A 73-year-old man presented with gross hematuria. Ultrasonography and computerized tomography showed small bladder tumors and a left renal mass protruding to renal pelvis. Transurethral resection of bladder tumor and ureteroscopic tumor biopsy were performed, and pathological examinations revealed transitional cell carcinoma in the bladder and renal cell carcinoma in the kidney. He underwent left radical nephrectomy. A 4-month postoperative cystoscopy revealed a solitaly non-papillary tumor in the bladder. Transurethral resection was performed and pathological diagnosis was metastasis from renal cell carcinoma. At that time, multiple metastases to ureteral stump and lung were found. He had undergone palliative treatment because of his poor general condition until he died 26 months postoperatively. Care should be taken for management of ureteral stump when diagnostic ureteroscopy was done for renal cell carcinoma invading the renal pelvis.     

Multifocal metastases of recurrent renal cell carcinoma successfully treated with a combination of low dose interleukin-2, α-interferon and radiotherapy

A 59-year-old man presented with a 2-month history of left flank pain and a possibility of gross hematuria. Left renal cell carcinoma stage II was diagnosed and radical left nephrectomy was performed. Twenty-two months postoperatively, lung metastases were demonstrated and 6 x 10(6) units of alpha-interferon (IFN-alpha) were administered for 9 months, only to keep the sizes of the metastases unchanged. Thirty-four months after the operation, liver metastases and bone metastasis in the left sacroiliac joint were revealed. The combination cytokine therapy was performed with 1.4 x 10(6) U of interleukin-2 (IL-2) and 3 x 10(6) U of IFN-alpha for 16 weeks, and the left sacroiliac joint metastasis was treated with radiation therapy of 4 Gy per day for 7 days. Six months after the 16 weeks of immunotherapy, computed tomography and bone scintigraphy revealed that the metastases of the lung, liver and bone substantially disappeared and this complete response is still kept after 16 months.     

Bilateral adrenal metastases from renal cell carcinoma: a case report

We report a case of renal cell carcinoma with bilateral adrenal metastases. A 57-year-old man was admitted to our hospital for a left renal mass. Computerized tomography and magnetic resonance imaging revealed a 4.5 cm left renal tumor and bilateral adrenal masses (3.0 cm on the right side and 2.0 cm on the left). A left nephrectomy and bilateral adrenalectomies were performed. The pathological findings showed clear cell carcinoma, G2 of left kidney metastasizing to both adrenal glands. The patient was administered supplementary hydrocortisone and was well 8 months after the nephrectomy and adrenalectomies without evidence of recurrence. Bilateral adrenal metastases from renal cell carcinoma are relatively rare. Our case seems to be the thirteenth case in the Japanese literature.     

Case of bilateral renal cell carcinoma with the tumor thrombus in the inferior vena cava

We describe a case of bilateral renal cell carcinoma with the tumor thrombus in the inferior vena cava. A 71-year-old male was admitted to our department for, careful examination of bilateral renal tumors. Abdominal computed tomography (CT) revealed bilateral solid enhanced renal masses with the tumor thrombus in the inferior vena cava (IVC) and the left renal vein. The renal tumor did not reveal distant metastatic lesions. We enforced two-term operation for bilateral renal tumor. First, right nephrectomy and tumor thrombectomy in the IVC were performed. On the 32th day after the first operation, we performed left nephrectomy. On the second day after the last operation, the patient received hemodialysis. The histopathological diagnosis revealed bilateral renal cell carcinomas. At 9 months after the last operation, the patient had multiple bone metastases, multiple liver metastases and multiple lung metastases.     

Inguinal lymph node metastasis of bladder carcinoma ten years after cystourethrectomy: a case report

A 79-year-old man had undergone radical cystourethrectomy for bladder carcinoma in January, 1989. Pathological report was Small cell carcinoma (SCC) > transitional cell carcinoma (TCC), G2 > G3, pT4 (prostate), ew (-). Ten years later, follow-up computed tomography (CT) revealed swollen left inguinal lymph node in October 1998 and lymph node dissection was performed in January, 2000. The pathological report showed TCC, G2. Left inguinal lymph node metastases appeared again in January, 2001. Chest X-ray films showed multiple lung metastases in March, 2001. Three couses of MVAC (methotrexate, vinblastine, doxorubicin cisplatinum) chemotherapy had been performed since September, 2001 but were in effective. Papillary tumor was observed at external urethral meatus in September, 2002 and the biopsied specimens showed TCC, G1 > G2, pathologically. Finally he died of respiratory insufficiency in January, 2003. It is suggested that the recurrent TCC tumor in the urethral remnants might metastasize into the inguinal lymph nodes.     

Evaluation of bone metastases from renal cell carcinoma

Forty-two cases of bone metastasis from renal cell carcinoma were examined. Thirty of the cases had bone metastases at the time of renal cell carcinoma. Bone metastasis appeared after treatment of the primary site in 12 cases. Fifteen cases had only bone metastasis and another 27 had metastasis in multiple organs. The total cause-specific survival curve of these patients was 10% at 5 years. All patients with bone metastases died of cancer within 5 years after the bone metastases had developed. There was no significant difference in the survival rate between patients with bone metastases and patients with lung metastases. We investigated the prognostic value of laboratory studies in bone metastases of renal cell carcinoma. However, no significant markers were detected for bone metastases. The 6 patients were treated with decompressed laminectomy (2), wide resection (3) and excision of the metastatic lesions (3). The quality of life was improved in all the patients although they died of cancer.     

Advanced renal cell carcinoma showing a different response to two types of interferon-alpha

Interferon (IFN)-alpha has been widely used in systemic therapy for advanced renal cell carcinoma (RCC). IFN-alpha is represented by a large family of structurally related genes expressing at least 14 subtypes, each of which shows quantitatively distinct patterns of biological activities. Although those distinct patterns of biological activities of IFN-alpha subtypes against renal cancer cell lines have been demonstrated, there is no report that demonstrates the difference in each subtype-induced antitumor activity in patients with RCC. Herein, we present a unique case of advanced RCC that is resistant to interleukin-2 and IFN-alpha administration, and we describe its response to another IFN-alpha administration. The difference between the two IFN-alpha types lies in the distribution of the subtypes: this case, therefore, suggests that the difference in the subtype distribution may cause the different response of the RCC. A 47 year-old male was diagnosed as left RCC with multiple lung metastases and underwent radical nephrectomy. The histological diagnosis was pT3b G2 clear cell carcinoma. He received intramuscular administration of 6 x 10(6) units of natural human IFN-alpha (Sumiferon) three times a week following the operation. However, the lung metastases showed progression. Thereafter, he received intravenous administration of 1.4 x 10(6) units of human interleukin-2 everyday. However, the lung metastases showed further progression and the hemoptysis, dyspnea, and chest pain deteriorated. Finally, he was given intramuscular administration of 5 x 10(6) units of another natural human IFN-alpha (OIF) three times a week. After the OIF administration, his complaints subsided and a chest CT scan revealed reduced lung metastases and diminished pleural effusion. He had not received any anti-tumor agents other than IFN-alpha or interleukin-2 since the operation. However, although he remained free of hemoptysis, dyspnea, and chest pain after OIF administration, the lung metastases increased again and multiple brain metastases were also observed five months after the first OIF administration. He died of metastatic RCC one year after the operation.     

Spontaneous disappearance of multiple lung metastases after nephroureterectomy from sarcomatoid carcinoma of the renal pelvis: A case report

We report a case in which lung metastases disappeared spontaneously after nephroureterectomy from sarcomatoid carcinoma of the renal pelvis. A 58-year-old man presented with gross hematuria. Computed tomography (CT) revealed a left renal tumor and multiple lung metastases. Intravenous pyelography revealed a filling defect in the upper renal calyx. Urine cytology was positive. Left renal pelvic cancer was diagnosed and nephroureterectomy performed. The resected specimen was diagnosed pathologically as sarcomatoid carcinoma of the renal pelvis. Approximately 5 months later, CT revealed that the lung metastases had disappeared. There has been no evidence of disease for 46 months postoperatively.     

Simultaneous contralateral testicular metastasis from a renal clear cell carcinoma.

The case of a 66-year-old male with a right renal cell carcinoma and a left testicular mass is reported. Radical nephrectomy and contralateral orchidectomy were performed. Histology revealed a metastasis of the renal cell carcinoma of clear cell type into the left testis. The patient died seven months post-operatively of disseminated lung metastases. The case demonstrates the multi-ocular metastatic potential of renal cell carcinoma.     

Intra-arterial infusion chemotherapy for liver metastases of testicular tumors: report of two cases

Two cases of testicular tumors with lymph node involvement and multiple lung and liver metastases were treated successfully with intra-arterial infusion chemotherapy. Case 1: A 30-year-old man presented with right scrotal swelling and an abdominal mass. He had a large retroperitoneal mass and multiple lung and liver metastases on computed tomographic (CT) scan and chest X-ray. Right inguinal orchiectomy was performed. Histopathological diagnosis revealed embryonal cell carcinoma and choriocarcinoma. Cisplatin, vinblastine, VP-16 and pepleomycin combination chemotherapy (PVeBV) was started and repeated for 2 courses. The retroperitoneal mass and lung tumors decreased in size, but liver tumors enlarged. Systemic and intrahepatic arterial infusion combined with chemotherapy was administered, and intra-arterial chemotherapy (cisplatin, VP-16) was added. The patient also received systemic chemotherapy (carboplatin, VP-16, ifosfamide). After chemotherapy, retroperitoneal lymph node dissection was performed. Microscopic examination revealed no viable cancer cells. On CT scan, no retroperitoneal, liver, or lung tumor was detected. Case 2: A 43-year-old man presented with right scrotal swelling and an abdominal mass. CT scan revealed a large retroperitoneal mass as well as lung and multiple liver metastases. Right inguinal orchiectomy was performed. Histopathological diagnosis revealed seminoma. Cisplatin, vinblastine, VP-16 and pepleomycin combination chemotherapy (PVeBV) was administered, but the liver tumors ware enlarged on CT scan. Intrahepatic arterial infusion chemotherapy (cisplatin, VP-16) was started and repeated for 4 courses. On CT scan, the lung metastasis seemed to have disappeared, and the retroperitoneal mass and liver metastases were decreased in size.     

Advanced renal cell carcinoma treated with granulocyte-macrophage colony-stimulating factor gene therapy: A clinical course of the first Japanese experience

A phase I study of granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor vaccine for patients with metastatic renal cell carcinoma (RCC) was initiated in 1998, as the first cancer gene therapy in Japan. The study is still ongoing, but the first patient is presented here as a case report. The patient was a 60-year-old man with Stage IV CRC with multiple lung metastases. After surgical resection of the tumor, autologous tumor cells were transduced and cultured to produce GM-CSF. The patient received a total of 2.2 x 108 gene-transduced autologous vaccine cells by subcutaneous injection. During the course of vaccination, growth of the largest metastatic mass slowed to some extent; however, multiple new lesions developed. About 1 month after the start of low-dose IL-2 therapy, rapid and remarkable regression in a large lung hilar metastatic mass was noticed. The patient died of progressive disease 7 months after the start of GM-CSF gene therapy. Careful histological examination by autopsy revealed that the responding mass was infiltrated by CD8 positive dominant T lymphocytes, and did not exhibit vasculitis or any other changes associated with active autoimmune disease.     

Active combination immunochemotherapy with interferon-alpha, interleukin-2 and gemcitabine for four patients with metastatic renal cell carcinoma

Immunochemotherapy consisting of interferon-alpha (IFN-alpha), interleukin-2 (IL-2), and gemcitabine (GEM) for metastatic renal cell carcinoma. A partial response maintained for 15 months, was obtained in one case resistant to IFN-alpha and IL-2 of para-aortic lymph node metastases (case 1). A minor response with 30% reduction of lung metastasis was obtained in one IFN-alpha resistant case, and the duration was 6 months (case 2). In one case, in contra-lateral renal metastasis, no disease progression was obtained for 6 months (case 3). One case with resistance to IFN-alpha and IL-2, and who had preoperative abnormalities of corrected serum calcium, serum c-reactive protein and hemoglobin, had progressive disease and died of cancer after 6 months (case 4). Grade 3 toxicity was noted in leucopenia (4/4), anemia (1/4), and nausea/ vomiting (1/4). Although the response duration was short, the combination immunochemotherapy consisting of IFN-alpha, IL-2 and GEM may be a promising salvage regimen for the patients with metastatic renal cell carcinoma.     

A case of metastatic renal cell carcinoma to the ovary

A 52-year-old woman had a pathological fracture of the right femur. On histopathological examination bone metastasis from renal cell carcinoma was suspected. Abdominal computed tomography showed a heterogeneous mass (9.1 x 7.8 x 6.5 cm) in the left kidney and a cystic multilocular mass (12 x 10 cm) in the pelvis. Bone scintigraphy revealed an abnormal uptake in the left coracoid process, right third rib, and right distal femur and proximal tibia. Clinical diagnosis was left renal cancer with multiple bone metastases (cT2NOM1, stage IV) and a right ovarian tumor. We performed left radical nephrectomy and resection of right ovarian tumor by bilateral adnexectomy. On histopathological examination, the left kidney tumor was diagnosed as renal cell carcinoma (clear cell carcinoma with chromophobe component, G2 > G1). The ovarian tumor consisted of carcinoma of clear cell type (G2) that resembled components of left renal cell carcinoma, confirming the diagnosis of metastatic renal clear cell carcinoma to the ovary. Although she underwent immunotherapy with interferon, she died 10 months after nephrectomy. Metastasis to the ovary from renal clear cell carcinoma is very rare and only 18 cases have been reported in the literature. This rarity may be related to the difficulty of differential diagnosis between metastatic renal cell carcinoma to the ovary and primary ovarian clear cell carcinoma. Elaborate analysis of microscopic features and immunohistochemical profiles may help in the distinction of this metastatic lesion.     

Bladder recurrence of renal cell carcinoma: report of two cases

We present two rare cases with renal cell carcinoma which recurred at urinary bladder. The first case is an 87-year-old female who had been undertaken right nephrectomy 17 years earlier. Through the examination of hypercalcemia, bone metastases and a bladder tumor were found. Transurethral resection of the bladder tumor was performed and histological examination revealed that the tumor was clear cell carcinoma similar to the right renal tumor. The second case is a 67-year-old male who had been undertaken left nephrectomy 4 and half years earlier. In spite of the adjuvant immunotherapy including interferon alpha, gamma and interleukin-2, 16 months later multiple lung metastases appeared. One month before admission he noticed asymptomatic hematuria. Cystoscopy revealed 3 non-papillary pedunculated tumors, which were resected transurethrally. Histologically the tumor was clear cell carcinoma similar to the left renal tumor. In both cases the metastasis was confirmed histologically. As in both cases the recurrent bladder cancers were confined in the mucosa, these metastases were thought to be caused by implantation.