Treatment with Sunitinib Enabled Complete Resection of Massive Lymphadenopathy not Previously Amenable to Excision in a Patient with Renal Cell Carcinoma

We present a case of previously unresectable lymphadenopathy in a patient with renal cell carcinoma treated with sunitinib. Complete resection of a 15-cm left renal cell carcinoma was initially impossible due to massive retroperitoneal disease and encasement of the great vessels and mesenteric vessels. Residual retroperitoneal disease from a radical nephrectomy was treated with the oral, multitargeted receptor tyrosine kinase inhibitor, sunitinib. Tumour shrinkage following five cycles of treatment allowed uncomplicated complete resection of the lymphadenopathy. Follow-up after 6 mo showed no evidence of disease recurrence.     

LACK OF RETROPERITONEAL LYMPHADENOPATHY PREDICTS SURVIVAL OF PATIENTS WITH METASTATIC RENAL CELL CARCINOMA

PURPOSE: Patients with metastatic renal cell carcinoma have a reported 5-year survival of 0% to 20%. The ability to predict which patients would benefit from nephrectomy and interleukin-2 (IL-2) therapy before any treatment is initiated would be useful for maximizing the advantage of therapy and improving the quality of life. MATERIALS AND METHODS: A retrospective analysis of the x-rays and charts of patients treated at the National Institutes of Health Surgery Branch between 1985 and 1996, who presented with metastatic renal cancer beyond the locoregional area and the primary tumor in place, was performed. Preoperative computerized tomography or magnetic resonance imaging, or radiological reports if no scans were available, were used to obtain an estimate of the volume of retroperitoneal lymphadenopathy. Operative notes were used to evaluate whether all lymphadenopathy was resected or disease left in situ, or if any extrarenal resection, including venacavotomy, was performed. Mean survival rate was calculated from the time of nephrectomy to the time of death or last clinical followup. If patients received IL-2 therapy, the response to treatment was recorded. Mean survival and response rate for IL-2 were compared among patients in 3 separate analyses. Patients without preoperatively detected lymphadenopathy were compared with those with at least 1 cm.3 retroperitoneal lymphadenopathy. Also, the patients who had detectable lymphadenopathy were divided into subgroups consisting of all resected, incompletely resected, unresectable and unknown if all disease was resected. Each subgroup was compared with patients without detectable preoperative lymphadenopathy. Patients with less than were compared to those with greater than 50 cm.3 retroperitoneal lymphadenopathy. Patients undergoing extrarenal resection at nephrectomy (complex surgery) due to direct invasion of the tumor into another intra-abdominal organ were compared with those undergoing radical nephrectomy alone, regardless of lymph node status. Statistical analysis was done with the Mantel-Cox test for comparison of survival on Kaplan-Meier curves and with Fisher's exact test for response rates for IL-2. RESULTS: A total of 154 patients with metastatic renal cell carcinoma underwent cytoreductive nephrectomy as preparation for IL-2 based regimens. There were 82 patients with metastatic renal cell carcinoma and no preoperative retroperitoneal lymphadenopathy who survived longer (median 14.7 months) than the 72 with lymphadenopathy (median 8.5, p = 0.0004). Patients with incompletely resected, unresectable or an unknown volume resected had decreased survival compared to those with no retroperitoneal lymphadenopathy. A multivariate analysis of survival was performed evaluating the known prognostic indicators, performance status and tumor burden, as represented by the number of organs involved with metastases, and the new prognostic factor, lymphadenopathy. Lymphadenopathy was more closely associated with survival than performance status, and appeared to be a new prognostic variable. Patients with and without retroperitoneal lymphadenopathy at initial presentation had similar rates for treatment with IL-2 (54% for both groups). Of the 82 patients with no lymphadenopathy 11 (13%) had long-term survival greater than 5 years. Of the 6 complete responses to IL-2, 5 occurred in this group. Only 1 other patient with incompletely resected retroperitoneal lymphadenopathy survived longer than 5 years. No significant difference in survival was seen between patients who did or did not undergo complex surgery. CONCLUSIONS: Patients who presented with metastatic renal cancer and retroperitoneal lymphadenopathy had a shorter survival than those with no detectable retroperitoneal lymphadenopathy. It is warranted to continue to perform complex extrarenal resection during nephrectomy since no significant difference in the response rate for IL-2 or mean survival compared with those of patients undergoing nephrectomy alone is currently detectable.     

Preoperative induction with sorafenib pathologically downstaged advanced renal cell carcinoma: A case report

We present the case of a patient with renal cell carcinoma treated preoperatively with sorafenib. Complete resection of the left renal mass measuring 7.2 × 6.6 cm seemed to be difficult at diagnosis because of large renal hilar lymph nodes. With a short period of sorafenib administration, marked shrinkage of the renal mass and lymphadenopathy was observed after the patient experienced fulminant hepatic failure and a severe hand–foot skin reaction. Two‐dimensional computed tomography revealed 60%, 78% and 84% reduction in the primary renal tumor, lung metastatic nodules and lymph nodes, respectively. Tumor shrinkage allowed for complete resection of the left kidney and the lymphadenopathy. Pathological findings revealed that over 90% of the renal tumor was substituted by necrotic fibrotic tissue and that the residual neoplastic component was diagnosed as clear cell carcinoma. The lymph nodes that were resected were negative for malignancy. At 6 months after radical nephrectomy, a new computed tomography scan revealed no evidence of disease with the disappearance of lung nodules.     

Tumors at the aortoiliac/inferior vena cava bifurcation: preoperative, anesthetic, and intraoperative considerations

Primary and recurrent retroperitoneal tumors can involve the aortoiliac vasculature. They are often considered inoperable or incurable because of the locally advanced nature of the disease or the technical aspects involved in safely resecting the lesion. Safe resection of these lesions requires experience and extensive preoperative planning for success. A retrospective database review of 76 patients with retroperitoneal tumors identified tumors involving major vascular structures in the abdomen and pelvis undergoing resection of tumor en bloc with the aortoiliac vasculature. Preoperative planning and intraoperative technical maneuvers are reviewed. Patients were followed until time of this report. Four patients with retroperitoneal tumors involving the aortoiliac vessels underwent surgery: two patients with sarcoma (one primary and one recurrent), one with metastatic renal cell carcinoma, and one with a paraganglioma. All patients had resection of the aorta and vena cava or the iliac artery and vein. Arterial reconstruction (anatomic or extra-anatomic) was performed in all cases. The patient with renal cell carcinoma also required venous reconstruction to support a renal autotransplant. Veno-venous bypass was required in one patient. Local control was achieved in 3 of 4 cases. Surgery for retroperitoneal tumors involving major vascular structures is technically feasible with appropriate planning and technique. Multiple disciplines are required, including general surgical oncology, vascular surgery, and possibly, cardiothoracic surgery.     

An adult Xp11.2 translocation renal carcinoma showing response to treatment with sunitinib

A rare variant of renal cell carcinoma (RCC) with a translocation involving Xp11.2 has become increasingly recognized as a separate entity in the 2004 World Health Organization (WHO) kidney carcinoma classification. These tumors predominantly affect children and young adults and tend to present with advanced stage disease. Although reported to be indolent in children, adult cases run a more aggressive course. Little is known about their natural history, prognosis and response to therapy.We report a case of Xp11 translocation renal cancer in a 33-year-old male patient who presented with widespread rapidly progressive metastatic disease involving extensive intra-thoracic lymph nodes, supra-clavicular, retroperitoneal lymph nodes, lung nodules, and peritoneal mass.He had failed to respond to treatment with high dose interleukin 2, but showed a significant clinical response to treatment with the multikinase inhibitor sunitinib. CT scan performed after 3 cycles (18 weeks) of therapy revealed more than 65% reduction of measurable disease by response evaluation criteria in solid tumors (RECIST) criteria, resolution of other assessable lesions, and a clinical benefit that lasted for over 13 months. But unfortunately, this was subsequently followed by a rapidly progressive course.The well-recognized clinical efficacy of multikinase inhibitors such as sunitinib and sorafenib is based on the outcomes in patients with clear cell histology. There is limited data on efficacy in non-clear cell RCC, but activity in translocation RCC has not been reported. To our knowledge, this is the first documented case of Xp11 translocation carcinoma to have demonstrated an objective durable response to sunitinib. It remains unclear how resistance to sunitinib develops, but the results to date support further evaluation of sunitinib in cases of translocation RCC.     

Testicular carcinoma with inferior vena cava thrombosis extending into the right atrium treated with chemotherapy and anticoagulation.

A 34-year-old male with pulmonary emboli and thrombosis of the inferior vena cava extending into the right atrium was found at presentation to have a mixed seminoma and embryonal cell testicular carcinoma with high-volume retroperitoneal disease and visceral metastases. The patient was free of disease 19 months after treatment with combination chemotherapy and anticoagulation followed by resection of the residual mass. We could not find any previous report of a patient with bulky retroperitoneal disease and vena cava thrombosis successfully treated with chemotherapy without vena cava resection.     

Pathological evidence of necrosis in recurrent renal mass following treatment with sunitinib

Sunitinib is a highly potent, selective vascular endothelial growth factor-receptor types 1 to 3, platelet-derived growth factor (PDGF)-R-alpha, and PDGF-R-ss. Preclinical data suggest that sunitinib (SU11248) has antitumor activity that may result from both inhibition of angiogenesis and direct antiproliferative effects on certain tumor cell types. Sunitinib resulted in tumor shrinkage in 80% of patients who had failed treatment with Bevacizumab and 13% of patients demonstrated an objective Response Evaluation Criteria in solid Tumors (RECIST) in a study presented at the 2006 American Society of Clinical Oncology (ASCO) meeting. We report the first published pathological evidence of sunitinib's effect on recurrent renal cell carcinoma. This was seen in a patient with renal cell carcinoma who developed a renal fossa recurrence 2 years following radical nephrectomy. Tumor shrinkage was evident in the nephrectomy bed after treatment with sunitinib. The pathology of the resected retroperitoneal mass and its implications are discussed.     

A case of small cell carcinoma of the ureter with SIADH-like symptoms

Primary small cell carcinoma of the ureter is very rare. We report a case associated with SIADH (syndrome of inappropriate secretion of ADH) -like symptoms. A 53-year-old man presented to our hospital with lower back and left lower quadrant abdominal pain. Computed tomography revealed left hydronephrosis, a peri-ureteral left lower quadrant mass, and retroperitoneal (RP) lymphadenopathy. Transduodendal biopsy of a RP lymph node revealed small cell carcinoma. He was referred to urology for further evaluation. Urography showed an obstructing mass invading the left ureter. Comprehensive metastatic evaluation revealed no other lesions. Thus, we diagnosed primary small cell carcinoma of the ureter with RP lymph node metastases. In addition, he developed SIADH-like symptoms, and we strongly suspected that it was due to ectopic production of ADH from this carcinoma. He was treated with systemic chemotherapy (methotrexate, epirubicin, and cisplatin). Following this, we performed radical nephroureterectomy with RP lymph node resection. However, he died of recurrent disease five months later.     

后腹腔镜肾盂癌根治性切除术后穿刺孔种植转移1例体会

目的:探讨后腹腔镜肾盂癌根治性切除术穿刺孔肿瘤种植的诊断治疗、预防措施等。方法:分析2004年9月诊治的1例后腹腔镜肾盂癌根治性切除术后穿刺孔肿瘤种植病例的临床资料。结果:该例肾盂癌患者行后腹腔镜肾输尿管全长及膀胱袖状切除术后3月发生穿刺孔种植转移,表现为穿刺孔处质硬肿块,病理证实为移行上皮癌,但无法找到原发病灶。行肿块扩大切除后辅以局部放疗及全身化疗,随访12个月,未见肿瘤复发及转移。结论:后腹腔镜肾盂癌根治性切除术可能引起术后穿刺孔肿瘤种植转移。经过系统的治疗,预后良好。认识其临床表现与发病机制,有利于更好的指导临床工作。     

Long-term response with sunitinib for metastatic renal cell carcinoma

A 65-year-old man with metastatic renal cell carcinoma developed progressive disease after treatment with interferon-alpha. He began treatment with sunitinib, a multitargeted tyrosine kinase inhibitor, on clinical trial. The patient achieved a partial response after two cycles of therapy, with a durable response continuing after 2 years of treatment. This case report illustrates the long-term response to sunitinib for patients with metastatic renal cell carcinoma.     

C‐reactive protein as a prognostic marker for advanced renal cell carcinoma treated with sunitinib

Objectives: To investigate the prognostic role of C‐reactive protein in patients with advanced renal cell carcinoma treated with sunitinib. Methods: A total of 41 consecutive patients with advanced clear‐cell renal cell carcinoma treated with sunitinib between December 2008 and August 2011 were included in this study. Logistic regression analysis estimated the relative importance of non‐tumor variables, including C‐reactive protein, and selected adverse events as predictive factors for sunitinib responses. Results: Overall, 11 patients (26.8%) showed a partial response and 10 patients (24.4%) had stable disease. On univariate analysis, Memorial Sloan‐Kettering Cancer Center non‐poor risk, normal C‐reactive protein, hand–foot skin reaction, altered taste, fatigue and leukopenia were significantly correlated with objective responses (P = 0.020, 0.001, 0.006, 0.006, 0.023 and 0.037, respectively). On multivariate analysis, normal C‐reactive protein was independently associated with objective response (P = 0.016). Patients with a normal level of C‐reactive protein (≤0.30 mg/dL) had a significantly higher partial response plus stable disease rate (84.6% vs 35.7%, P = 0.002) and significantly longer progression‐free survival (median 19.0 vs 6.0 months, P = 0.036) than patients with an elevated level of C‐reactive protein. Conclusions: C‐reactive protein is an independent prognostic indicator for patients with advanced renal cell carcinoma treated with sunitinib.     

Long-term survival in a patient with node-positive adult-onset Xp11.2 translocation renal cell carcinoma

Adult-onset Xp11.2 translocation renal cell carcinoma is a rare malignancy that has an aggressive clinical course and poor prognosis. The reasons for this include the fact that most patients have an advanced clinical stage at diagnosis and also that there is a lack of effective systemic therapy. We herein present the case of a 32-year-old woman suffering from node-positive Xp11.2 translocation renal cell carcinoma who underwent radical nephrectomy with an extensive retroperitoneal lymph node dissection, followed by two times of surgical resection for recurrent nodal disease. The patient has experienced no recurrent disease 4.5 years after the last operation and remains free of disease. Surgical approach to recurrent disease, if the recurrent site can be judged to be limited, might be one of the feasible treatment options in patients with Xp11.2 translocation renal cell carcinoma.     

Treatment of Abdominal Malignancy Invading the Vena Cava: A Report of Seven Cases

Retroperitoneal tumors and other abdominal malignancies invading the inferior vena cava can be treated surgically when no metastases are present. We resected four retroperitoneal tumors, two renal cell carcinomas, and one gastrointestinal stromal tumor with a concomitant caval resection. Although meticulous care is required when manipulating the major vessels, long-term survival with an improvement in the quality of life was achieved. These cases are described, with particular focus on the management of the major vessels.     

Stereotactic body radiotherapy-induced abscopal effect twice after pembrolizumab failure in hereditary leiomyomatosis and renal cell carcinoma: a case report with genetic and immunologic analysis

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare but aggressive disease. Immune checkpoint inhibitors (ICIs) have been an indispensable component for the management of advanced renal cell carcinoma, and stereotactic body radiotherapy (SBRT) has offered additional immunological effect boost for improving the treatment outcomes of the patients. However, the synergistic effect of ICIs with SBRT in HLRCC remains largely unexplored. We present the case of a 34-year-old woman with advanced HLRCC who underwent radical nephrectomy but soon relapsed at the retroperitoneal lymph nodes (RPLN). She was prescribed sunitinib but still progressed on twenty cycles with bulky RPLN and ascites. She was then treated with axitinib and pembrolizumab for twenty months, and received SBRT for the progression of RPLN upon which the first abscopal effect was observed via significant shrinkage of in-field and out-field tumor lesions. Five months later, she underwent a second course of SBRT for pelvic mass progression and the second abscopal effect was observed. Genetic and immunologic characteristics revealed a large number of tumor-infiltrating immune cells and high levels of PD-L1 expression. This case report demonstrates the synergistic effect of ICIs and SBRT in HLRCC and the potential mechanism for the repeated SBRT-induced abscopal effect, supporting the application of SBRT to oligometastatic lesion during ICIs treatment to delay disease progression. Further studies are needed to verify the strategy of combining ICIs and SBRT in advanced HLRCC.     

肾癌区域淋巴结转移的临床分析

目的 了解肾癌区域淋巴结转移的临床特点及发生发展规律,提高对本病的诊治效果.方法 回顾性分析2004年1月至2008年12月19例肾癌伴有区域淋巴结转移患者的资料.男15例,女4例.年龄29～77岁,中位年龄57岁.肿瘤位于左肾12例,右肾7例.腹膜后肿大淋巴结最大径1.5～5.0 cm,中位数2.8 cm,其中4例影像学检查未发现肿大淋巴结,术中探查证实.行腹膜后肿大淋巴结切除11例,区域淋巴结清扫8例.结果 肾癌发生区域淋巴结转移占同期收治肾癌的1.6%(19/1213).术后19例均获随访,随访时间8～78个月,中位数34个月.无瘤生存6例,带瘤生存7例,死亡6例,5年生存率68.4%.腹膜后区域淋巴结清扫组与肿大淋巴结切除组生存期及术后复发转移率比较差异均无统计学意义(P=0.644;P=0.319).结论 肾癌发生单纯区域淋巴结转移少见,术前影像学可能漏诊,部分患者通过区域淋巴结清扫或肿大淋巴结切除可获得无瘤生存.

Abstract：

Objective To discuss the characteristics of renal cell carcinoma with regional lymph node metastasis at diagnosis. Methods The data of 19 patients diagnosed with renal cell carcinoma with regional lymph node metastases at diagnosis from January 2004 to December 2008 were reviewed.The median age was 57 years (29-77).The study group included 15 males and four females.The primary tumor was located in the left kidney in 12 patients and fight in seven patients.The median maximam diameter of retroperitoneal lymph nodes was 2.8 cm(1.5-5.0).The lymph nodes in four patients were not detected by the preoperative image examination,but were confirmed by intraoperative exploration.Eleven cases had enlarged retroperitoneal lymph nodes resected and eight had regional lymph nodes dissected. Results The patients with regional lymph node metastases at diagnosis of renal celI carcinoma accounted for 1.6% (19/1213) of the total renal cell carcinoma cases.With a median follow-up of 34 months,six patients were survival without progression,and seven were survival with progression.giving a 5-year survival rate of 68.4%.The survival and recurrence rates after surgery were not significantly different by Fisher test(P=0.644 and 0.319 respectively) between the patients who underwent retroperitoneal regional lymph node dissection and those who underwent enlarged lymph node resection. Condmiom Renal cell carcinoma with regional lymph node metastasis at diagnosis is uncommon.Some patients may achieve long-term tumor-free survival through regional lymph node dissection or enlarged Iymph nodes resection.     

Dramatic reduction in tumor burden with neoadjuvant sunitinib prior to bilateral nephron-sparing surgery

Neoadjuvant sunitinib has recently been described for the management of renal cell carcinoma. We present the pre and posttreatment images of a 49-year-old male with bilateral biopsy-proven clear cell renal cell carcinoma who underwent treatment with sunitinib prior to nephron-sparing surgery. After four four-week cycles of daily 50 mg sunitinib, the patient demonstrated a dramatic reduction in tumor burden allowing for successful bilateral partial nephrectomy.     

Vascular injury and repair associated with retroperitoneal lymphadenectomy for nonseminomatous germinal cell tumours of the testis.

Metastatic disease adjacent to major vascular structures in the retroperitoneum sometimes necessitates planned removal of portions of these vessels, or the vessels may inadvertently be injured when retroperitoneal lymphadenectomy is performed. In 78 patients who underwent retroperitoneal lymphadenectomy, 17 (22%) required vascular repair intraoperatively. The vena cava was most frequently involved (eight cases) followed by inadvertent injury to the renal arteries (five cases) or the infrarenal aorta (three cases). Resection of the infrarenal aorta was planned in two cases without postoperative complication. In six cases a resection of either the whole inferior vena cava or a portion of it was needed to remove all of the tumour. There were nine cases of inadvertent injury to the aorta, vena cava or a renal artery. The outcome after arterial repair was satisfactory with the exception of the inadvertent renal artery injuries, which required nephrectomy in three cases. Leg swelling was not a long-term sequela of either caval repair or resection.     

Response of renal lesions during systemic treatment with sunitinib in patients with metastatic renal cell carcinoma: a single center experience with 14 patients

Purpose  

The tyrosine kinase inhibitor (TKI) sunitinib induces partial remissions (PR) in a substantial proportion of patients with metastatic renal cell carcinoma (mRCC). Only little is known about the activity of sunitinib in renal lesions in patients with metastatic disease, as most patients with synchronous metastases receive palliative nephrectomy.     

后腹腔镜水刀辅助零阻断肾部分切除术治疗T_(1a)肾肿瘤的临床体会(附8例报告)

目的:探讨后腹腔镜水刀辅助零阻断肾部分切除术治疗T1a期肾肿瘤的临床经验与疗效。方法:回顾分析2011年10月至2012年11月8例T1a期肾肿瘤患者的临床资料,其中男6例,女2例,平均(38.2±10.4)岁,左侧5例,右侧3例;肿瘤直径平均(2.8±0.9)cm。8例患者均行后腹腔镜水刀辅助零阻断肾部分切除术。结果:8例手术均顺利完成,无一例中转开放手术,围手术期无严重并发症发生。手术时间平均(103.2±24.5)min,术中出血量平均(250.3±80.6)ml,肾周引流管平均留置(6.3±2.6)d,术后平均住院(8.3±1.6)d。术后平均随访(5.2±2.1)个月,患者肾功能正常,未见肿瘤复发及转移。结论:后腹腔镜水刀辅助零阻断肾部分切除术治疗T1a肾肿瘤安全、有效、患者创伤小,可避免残留肾脏组织的热缺血及缺血再灌注损伤,在肿瘤彻底切除的基础上肾功能得到最大限度地保留;但远期疗效尚需大样本研究及长期随访。     

Sunitinib efficacy against advanced renal cell carcinoma

PURPOSE: We assessed the efficacy of the oral multitargeted tyrosine kinase inhibitor sunitinib in patients with metastatic clear cell renal cell carcinoma. MATERIALS AND METHODS: Patients with metastatic clear cell renal cell carcinoma were enrolled in this multicenter, phase II clinical trial. Major eligibility requirements were clear cell renal cell carcinoma histology, prior nephrectomy, measurable metastases and failed prior cytokine therapy as a result of disease progression. Sunitinib was given orally as second line therapy in 6-week cycles of 50 mg daily for 4 weeks, followed by 2 weeks off drug per treatment cycle. Response to sunitinib was rigorously assessed by an independent third party core imaging laboratory (central review). RESULTS: Of 106 patients enrolled in the study 105 were evaluated for response. As determined by independent third party assessment, the objective response rate was 33% (95% CI 24%-43%) with a median response duration of 14.0 months. Median time to progression and median progression-free survival in the 105 evaluable patients was 10.7 and 8.8 months, respectively. Median survival was 23.9 months and 43 patients remained alive at a median followup of 29.7 months. CONCLUSIONS: The results of this trial demonstrate the efficacy of sunitinib for metastatic renal cell carcinoma. The optimal integration of surgery and sunitinib treatment requires further prospective investigation.