Author Affiliations: Department of Surgery (Dong J), Department of General Surgery (Cong L, Zhang TP and Zhao YP), and National Laboratory of Medical Molecular Biology (Zhao YP), Chinese Academy of Medical Sciences, Medical College Hospital, Peking Union Medical College, Beijing 100730, China

Corresponding Author: Yu-Pei Zhao, MD, PhD, Department of General Surgery, Peking Union Medical College Hospital and National Laboratory of Medical Molecular Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China (Tel: +86-10-65296007; Fax: +86-10-65124875; Email: zhaoyp8028@163.com)

 

© 2016, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(16)60052-8

Published online January 7, 2016.

 

 

Contributors: DJ and CL proposed the study. ZTP and ZYP took care of the patients from PUMCH. DJ and CL performed the research and wrote the first draft. DJ searched the databases and analyzed the data. ZTP and ZYP reviewed the draft and gave comments. All authors contributed to the design and interpretation of the study and to further drafts. ZYP is the guarantor.

Funding: None.

Ethical approval: Not needed.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

 

 

BACKGROUND: Renal cell carcinoma (RCC) is a common cancer, but pancreatic metastasis of RCC is unusual. Because of the rarity and peculiarity, pancreatic lesions from RCC metastasis were described mostly in case reports which highlight the importance of a systematic analysis of this clinical condition.

 

DATA SOURCES: Data of 7 patients with pancreatic metastasis of RCC treated in the Peking Union Medical College Hospital were extracted and 193 similar patients reported in the past 10 years from the literature were analyzed. Epidemiological, pathological and follow-up information were investigated. Potential prognostic factors were compared with corresponding data reported 10 years ago.

 

RESULTS: Multivariate Cox regression showed that asymptomatic metastasis and surgical procedure were independent factors associated with better survival. Compared with the data reported 10 years ago, follow-up of RCC patients has been emphasized in recent years, and atypical surgery is frequently used since it has similar effect as typical surgery on tumor resection while it is able to preserve more pancreatic function.

 

CONCLUSION: Surgical treatment should be an option as long as the pancreatic metastasis of RCC is resectable.

 

KEY WORDS: pancreatic metastasis; renal cell carcinoma; surgery; prognostic factor; survival analysis

According to the American Cancer Society report, renal cell carcinoma (RCC) is the sixth most common cancer in the United States, accounting for an estimated 13 860 deaths in 2014.^[1] Among patients with RCC, 20%-30% have metastases at presentation and up to 40%-50% develop widespread metastatic disease after nephrectomy.

 

The pancreas is an uncommon location for metastasis from other primary cancers and pancreatic metastases account for less than 5% of all pancreatic malignancies.^[2,3] A variety of cancers have been shown to metastasize into the pancreas, such as colon cancer, non-small cell lung cancer, and melanoma. In particular, RCC shows, besides metastases to lymph nodes, lung, liver and bones, an increased disposition for metastasis to rare sites, such as the thyroid gland and the pancreas.^{[4, 5]}

 

Finding reliable prognostic factors for patients with RCC metastatic to the pancreas would facilitate selection of different treatment strategies. A number of articles have proposed several prognostic models to predict the survival of these patients and showed different results. Some suggested that surgeons should preserve as much pancreatic tissue as possible to protect exocrine and endocrine function of the pancreas,^[6] whereas others suggested atypical tumor resection might lead to higher morbidity and recurrence rates.^[7]

 

Due to the rarity and peculiarity, pancreatic lesions for RCC metastasis were described mostly in case reports. In 2006, Sellner and colleagues^[8] conducted a high volume systemic research which thoroughly reviewed the literature of RCC with pancreatic metastasis from 1952 to 2003. In this study, we reviewed cases reported at the Peking Union Medical College Hospital (PUMCH) in the past decade and compared the relevant factors between our data and Sellner’s, attempting to identify the differences which could help investigate the underlying changes during the past 10 years. This study is to perform a systematic review of previous reports on patients with RCC metastasized to the pancreas and those with this condition admitted to our center, to portrait the characteristics of this condition, and to investigate the prognostic factors in this population.

 

 

Firstly, we performed a literature search in PubMed (2003 to 2014). The key words used were as follows: pancreatic metastasis, renal cell carcinoma, kidney cancer and surgery. The search was conducted using the term “related article”. All selected articles were studied and then screened to match pre-defined criteria. Articles containing duplication of case descriptions were excluded. Articles not containing individual patient data were excluded. And patients who were pathologically proved to have tumor other than clear cell carcinoma were excluded. As a result, 70 articles were included in the study.^{[6, 8-76]} Secondly, patients treated for pancreatic metastasis of RCC at our center (PUMCH) were included to expand patient population. Data for each patient were collected retrospectively, and the patients were followed up with clinical visits and telephone.

 

A total of 200 patients (193 from the literature and 7 from our center) were included in this study. The following data were extracted from the literature or our patients: patient characteristics, primary RCC, pancreatic metastasis, pancreatic surgery or other therapies performed, overall survival and date of death. Surgery strategies were classified into two categories: typical resection (pancreatoduodenectomy, distal pancreatectomy, total pancreatectomy) and atypical resection (enucleation and others).

 

All these data were analyzed with SPSS statistical software (version 13.0; IBM Corporation, Armonk, NY). Continuous data were present as mean and standard deviation. Potential risk factors for survival were first analyzed with univariate Cox regression. Variables with P<0.10 by univariate analysis were further analyzed by multivariate Cox regression. The clinically significant parameters (P<0.05) were then considered independent predictors of survival. The Kaplan-Meier method was then applied to depict survival curves and to compare the survival of patients with different distributions of these significant parameters. A subgroup evaluation utilizing the Kaplan-Meier method and the log-rank test was conducted to compare the prognosis of patients with typical surgery and atypical surgery. Moreover, to delineate the changes in the management of this patient population, we compared the patient characteristics and treatment options using Student’s t test (continuous variables) and binomial distribution test (categorical variables). For all analyses, a P value <0.05 was considered statistically significant.

 

 

A total of 7 patients with RCC metastatic to the pancreas, 4 men and 3 women with a mean age of 59 years (range 45-68), were treated in our center (Table 1). All the pancreatic metastases were metachronous. The average interval time between the renal tumor resection and the finding of pancreatic lesions was 6.91 years (range 1.17-17.00). Six patients presented with right renal tumors, 5 were symptomatic when metastatic lesions were found: two had abdominal pain, two had jaundice, and one suffered from upper gastrointestinal bleeding. The lesions were solitary in 3 patients, located in the head of the pancreas in 5 patients, and had a mean size of 3.81 cm (range 1-6). One of our patients had extrapancreatic metastasis of disease (liver). Surgical approaches for pancreatic lesions were taken in 5 patients, among whom 4 stayed alive with disease recurrence at 1, 14, 48 and 76 months after surgery, while one had no evidence of disease at 7 months after the resection. One patient did not receive any treatment due to personal reasons and another patient chose chemotherapy (hepatic artery infusion chemotherapy with mitomycin and epirubicin) because the lesions were deemed as unresectable. These two patients (without surgical interventions) died from the tumor at 2 and 11 months after diagnosis, respectively.

 

The characteristics of the patients included are summarized in Table 2. The information on age and gender was available in 188 patients. There were 109 men and 79 women with a mean age of 63.5 years (range 43-86). Primary renal tumors from left kidney were in 65 patients (59.6%), right in 43 (39.5%) and bilateral in 1 (0.9%). The stages of primary renal carcinoma were documented in 20 patients: 5, 10, 4 and 1 patients diagnosed with G1, G2, G3 and G4 grade of RCC, respectively. In 11 patients (5.5%), pancreatic metastases were synchronous with RCC. The mean interval time from nephrectomy to pancreatic metastasis was 9.9 years (range 0.17-27).

 

Most patients were clinically asymptomatic, and the diagnoses of pancreatic metastasis were incidental during follow-up, mostly detected as hypervascular lesions localized in the pancreas by CT or ultrasound screening. In 51 patients (38.9%), clinical symptoms were present upon diagnosis: abdominal pain in 21 patients, jaundice in 16, upper gastrointestinal bleeding in 5, weight loss in 9, melena in 3, anemia in 1, fever in 1, dizziness in 1, neck mass in 1, and fatigue in 1. In 68 patients, symptoms were not specified.

 

Pancreatic metastases were located in the head of the pancreas in 61 patients (35.9%), body in 20 (11.8%) and tail in 39 (22.9%); 50 patients (29.4%) had lesions metastasized to multiple pancreatic locations. The lesions were solitary in 110 patients (60.4%), with a mean size of 3.91cm (range 1-12).

 

Information of treatment strategies was available in 186 patients. Of them, 151 patients (81.2%) underwent surgical resection, 112 of them were subjected to resections with typical procedures including pancreatoduodenectomy (31), total pancreatectomy (37), and distal pancreatectomy (44) and 39 patients underwent resections with atypical procedures including enucleation (14) and other types of procedures (25). In 35 patients (18.8%), surgery was not performed due to locally advanced diseases or personal reasons. Fourteen of the 35 patients received adjuvant therapies.

 

Pathological information of the lesions in the pancreas was documented in only a few papers. Among the evaluable patients, 49 (87.5%) had clear margins whereas 7 (12.5%) had involvement at cut edges; and 39 (90.7%) had negative lymph nodes whereas 4 (9.3%) had lymph node metastases.

 

Follow-up data were available for 173 patients. 136 patients (78.6%) who were alive at the end of observation had a mean follow-up of 31.8 months (range 1-137). Among these patients, disease recurrences, including pancreatic and extrapancreatic recurrences, were found in 46 patients (26.6%). Thirty-seven patients (21.4%) died at a mean of 21.9 months (range 0.6-96).

 

Univariate Cox regression analysis identified four significant predictors of patient survival (Table 3). Symptomatic metastases (HR=2.19; 95% CI: 1.01-4.79), margin involvement (HR=8.05; 95% CI: 1.99-32.55) and lymph node involvement (HR=7.04; 95% CI: 1.16-42.7) were associated with poor survival. Surgical intervention (HR=0.29; 95% CI: 0.15-0.59) was a predicator for better prognosis. Subsequently, Kaplan-Meier survival curves were used to identify the differences in survival of patients based on the presence of the significant risk factors (Fig.). Moreover, a Kaplan-Meier analysis and the log-rank test showed no changes (P=0.94) in survival of patients undergoing typical surgery compared with those having atypical surgery (Fig.).

 

A multivariate Cox regression was then performed to determine the independent prognostic factors for patients with RCC metastatic to the pancreas. The variables were incorporated in a multivariate Cox regression (P<0.10). Since resected margin and lymph node affection were not specified in the majority of patients, the two factors were not included in the multivariate analysis. The results showed that symptomatic metastasis (HR=2.42; 95% CI: 1.01-5.40) and surgical intervention (HR=0.15; 95% CI: 0.03-0.67) were clinical significant and independent predictors for survival (Table 4).

 

In 2006, Sellner et al^[8] conducted a systemic review about the literature of RCC with pancreatic metastasis published from 1952 to 2003. In 236 patients reviewed, age, gender, interval time, metastasis number, metastasis location, metastasis size, surgery procedure and survival time were analyzed. The authors concluded that radical removal of metastases should be done in eligible patients.

 

In our study, we also analyzed the parameters such as age, gender, interval time, metastasis number, metastasis size and surgical procedure. Further, to delineate the changes in patient characteristics and treatment options in the past decade, we compared the relevant factors between our population and Sellner’s to detect differences which could help to investigate the underlying changes during the past 10 years (Table 5). The comparison revealed that the rates of metachronous metastasis and atypical surgical procedures were higher in the last decade than a decade ago (P<0.05).

 

 

RCC is a common cancer type. When the tumor is limited and remains in stage 1, it is characterized by a high 5-year survival rate (up to 95%).^[77] However, once it develops widespread metastases, the 5-year survival rate of the patients will drop to less than 10%.^[78]

 

Pancreatic metastasis accounts for 2%-5% of pancreatic malignancies. However, it seems to be related to a relatively good prognosis and leads to a different therapy strategy.^[79] Therefore, it is very important to preoperatively diagnose pancreatic metastasis. Solitary pancreatic metastases are difficult to differentiate and may be misdiagnosed as primary pancreatic cancer. However, imaging methods, such as CT and MRI, may help to discriminate between them. Peripherally enhanced tumors are more likely to be metastatic than primary pancreatic cancers, which tend to be non- or poorly-enhanced masses.^[80] At the same time, the diagnostic workup for tumors in the pancreas needs a meticulous elaboration of the medical history of patients, especially for those with a longer disease-free period. In our study, the percentage of metachronous metastasis was 94.5% vs 87.9% as indicated in Sellner’s article (P<0.01), suggesting that more patients with RCC are developing metachronous pancreatic metastasis than those seen a decade ago. This may due to medical progress and long-life of RCC patients as well as patients with pancreatic metastasis of RCC being followed up more closely than before.

 

A consensus on the efficacy of surgery in RCC patients has been reached with thorough and systemic review.^{[3, 8]} However, it is still controversial whether to perform typical or atypical procedures: some prefer atypical procedures and suggest that surgeons should dig out only the metastatic lesions to protect exocrine and endocrine function of the pancreas,^[6] whereas others support typical procedures and suggest that atypical procedures may lead to higher morbidity and recurrence.^[7] Our results revealed that surgical interventions could prolong patients’ survival. But there was no survival benefit from typical procedures compared with atypical ones. We also found that during the past decade, fewer patients (60% vs 72%, P=0.03) received typical operations, indicating that more surgeons prefer atypical procedures because of its effectiveness in preserving pancreas function. In the current therapeutic environment, pancreatic metastases of RCC represent a relatively indolent tumor phenotype, which further supports the strategy of atypical operation.^{[81, 82]}

 

The emergence of targeted therapy has provided more treatment options for this subset of patients. Recently, Grassi et al^[83] retrospectively studied patients with metastatic RCC treated with targeted therapy. In their cohort, there were 24 patients with pancreatic metastases and 8% received surgical treatment. However, many of the patients had multiple metastatic sites other than the pancreas and the authors did not focus on the comparison between the surgery group and non-surgery group. Still, the authors concluded that the presence of pancreatic metastasis seems to be associated with a longer survival other than the presence of metastasis at the sites which supported a less aggressive treatment strategy (eg. atypical surgery) for this subset of patients. Currently, we recommend surgical treatment for symptomatic patients and those with solitary lesions and no metastatic sites other than the pancreas. Surgical procedures could differentiate solitary metastasis from neuroendocrine neoplasms and symptomatic patients could benefit from surgeries to improve quality of life. However, the recommendation needs further evidence to support. Our study suggested a relationship between symptoms at the time of metastasis and prognosis. Univariate and multivariate analyses revealed that compared with metastatic patients without symptoms, symptomatic metastasis indicated a poor prognosis (both P<0.05). Similar findings have been reported previously.^[8] Like most tumors, clinical symptoms of pancreatic metastasis may be evidenced by tumor enlargement, necrosis, depletion and invasion. The results showed that close follow-up for patients with RCC is essential to find possible metastasis in the early phase.

 

Our study has three limitations. First, it is a retrospective study that inevitably influenced by selection bias, the baseline characteristics and indications for surgery were not the same in our patients. Therefore, although there was a significant relationship between surgery and prognosis, a causal relationship could not be established in our patients. Patients who did not undergo surgery might have locally unresectable tumors, poor performance status, and severe extrapancreatic diseases, which may interfere with the decision-making of surgeons. And these might also contribute to a poorer survival rate. Second, most of the included studies were case reports. Patient information described in these articles was not intact and many data were missing. In our study, only 4 articles mentioned adjuvant therapy of 19 patients. Hence it was difficult to assess the efficacy of adjuvant therapy in these patients. Moreover, patient preference, surgeon referral patterns, and evaluation of resectability could have introduced additional bias into the study. Although a prospective, randomized controlled study would draw an accurate conclusion, pancreatic metastasis of RCC is rarely detected in a single center.

 

In 1999, Memorial Sloan-Kettering Cancer Center (MSKCC) identified five prognostic factors for metastatic RCC (performance status, lactate dehydrogenase level, hemoglobin level, corrected serum calcium level, and disease-free survival from nephrectomy) to predict the outcome of patients with metastatic RCC.^[84] In 2005, this model known as the MSKCC prognostic model was validated and modified, adding prior radiotherapy and metastatic sites instead of performance status as prognostic factors.^[85] In 353 patients with metastasis RCC, their prognosis could be precisely predicted by the model. The patients were classified into 3 different risk groups: good, mediate and poor prognosis groups by the model. Then the effect of surgical procedure was examined in each group. This method can eliminate the selection bias of baseline characteristics of patients and can be conducted in a single center. Unfortunately, only few articles provided the above findings. Other than the MSKCC model, metastatic sites of RCC is another risk factor for patients’ prognosis: while metastasis to the lymph nodes, liver and brain suggests worse survival, metastasis to the pancreas is associated with better prognosis.^{[81, 82]} Unfortunately, we were unable to analyze the prognostic role of extrapancreatic metastatic sites due to lack of precise documentation in most cases of our study.

 

In conclusion, when pancreatic metastases of RCC are resectable, surgical treatment might be an option as long as no comorbidities are contraindicated for resection. The optimal resection strategy involves adequate resection margins and maximal tissue preservation of the pancreas. Therefore, atypical surgery, related to better survival in our cohort, should be taken into consideration. A rigid follow-up scheme for these patients, including a regular follow-up with ultrasound and CT is necessary so that any possible metastases could be found before symptoms occur.

 

 

1 American Cancer Society. Cancer Facts & Figures 2014. Atlanta: American Cancer Society;2014.http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-041770.pdf

2 Roland CF, van Heerden JA. Nonpancreatic primary tumors with metastasis to the pancreas. Surg Gynecol Obstet 1989;168:345-347. PMID: 2928909

3 Faure JP, Tuech JJ, Richer JP, Pessaux P, Arnaud JP, Carretier M. Pancreatic metastasis of renal cell carcinoma: presentation, treatment and survival. J Urol 2001;165:20-22. PMID: 11125354

4 Skinner DG, Colvin RB, Vermillion CD, Pfister RC, Leadbetter WF. Diagnosis and management of renal cell carcinoma. A clinical and pathologic study of 309 cases. Cancer 1971;28:1165-1177. PMID: 5125665

5 Ritchie AW, Chisholm GD. The natural history of renal carcinoma. Semin Oncol 1983;10:390-400. PMID: 6665566

6 Markinez I, Jiménez R, Ruiz I, Villarreal E, Lizarazu A, Borda N, et al. Pancreatic metastases due to renal carcinoma. Our cases and a literature review. Cir Esp 2013;91:90-95. PMID: 23041102

7 Georgios CS, Hauke L, Chao L, Brokalaki EI, Molmenti E, Broelsch CE. Surgical treatment of pancreatic metastases of renal cell carcinoma. JOP 2005;6:339-343. PMID: 16006684

8 Sellner F, Tykalsky N, De Santis M, Pont J, Klimpfinger M. Solitary and multiple isolated metastases of clear cell renal carcinoma to the pancreas: an indication for pancreatic surgery. Ann Surg Oncol 2006;13:75-85. PMID: 16372157

9 Aimoto T, Uchida E, Yamahatsu K, Yoshida H, Hiroi M, Tajiri T. Surgical treatment for isolated multiple pancreatic metastases from renal cell carcinoma: report of a case. J Nippon Med Sch 2008;75:221-224. PMID: 18781045

10 Akatsu T, Shimazu M, Aiura K, Ito Y, Shinoda M, Kawachi S, et al. Clinicopathological features and surgical outcome of isolated metastasis of renal cell carcinoma. Hepatogastroenterology 2007;54:1836-1840. PMID: 18019729

11 Andoh H, Kurokawa T, Yasui O, Shibata S, Sato T. Resection of a solitary pancreatic metastasis from renal cell carcinoma with a gallbladder carcinoma: report of a case. Surg Today 2004;34:272-275. PMID: 14999544

12 Assouad J, Banu E, Brian E, Pham DN, Dujon A, Foucault C, et al. Strategies and outcomes in pulmonary and extrapulmonary metastases from renal cell cancer. Eur J Cardiothorac Surg 2008;33:794-798. PMID: 18304831

13 Bahra M, Jacob D, Langrehr JM, Glanemann M, Schumacher G, Lopez-Hänninen E, et al. Metastatic lesions to the pancreas. When is resection reasonable? Chirurg 2008;79:241-248. PMID: 17717640

14 Bar C, Negru D, Ursulescu C, Crumpei F, Georgescus S. Pancreatic metastases. A case report--solitary pancreatic metastasis from a clear cell renal cell carcinoma. Rev Med Chir Soc Med Nat Iasi 2006;110:646-649. PMID: 17571560

15 Barbaros U, Sümer A, Demirel T, Karakullukçu N, Batman B, Içscan Y, et al. Single incision laparoscopic pancreas resection for pancreatic metastasis of renal cell carcinoma. JSLS 2010;14:566-570. PMID: 21605524

16 Béchade D, Palazzo L, Fabre M, Algayres JP. EUS-guided FNA of pancreatic metastasis from renal cell carcinoma. Gastrointest Endosc 2003;58:784-788. PMID: 1459532

17 Beck J, Bellmunt J, Escudier B. Long-term stable disease in metastatic renal cell carcinoma: sorafenib sequenced to sunitinib and everolimus: a case study. Med Oncol 2011;28:1379-1383. PMID: 20593250

18 Carrafiello G, Laganà D, Recaldini C, Dionigi G, Boni L, Bacuzzi A, et al. Radiofrequency ablation of a pancreatic metastasis from renal cell carcinoma: case report. Surg Laparosc Endosc Percutan Tech 2008;18:64-66. PMID: 18287986

19 Chara L, Rodríguez B, Holgado E, Ramírez N, Fernández-Rañada I, Mohedano N, et al. An unusual metastatic renal cell carcinoma with maintained complete response to sunitinib treatment. Case Rep Oncol 2011;4:583-586. PMID: 22220154

20 Crippa S, Angelini C, Mussi C, Bonardi C, Romano F, Sartori P, et al. Surgical treatment of metastatic tumors to the pancreas: a single center experience and review of the literature. World J Surg 2006;30:1536-1542. PMID: 16847716

21 Dar FS, Mukherjee S, Bhattacharya S. Surgery for secondary tumors of the pancreas. HPB (Oxford) 2008;10:498-500. PMID: 19088939

22 De Fazio S, Destito C, Ricciardi V, Marin AW. Pancreatic metastasis of renal cell carcinoma: a case report and review of the literature. G Chir 2004;25:351-355. PMID: 15756958

23 De Jesus CM, Corrêa LA, Filho JC. Surgical treatment of metachronous metastases in different organs following radical nephrectomy. Int Braz J Urol 2003;29:238-240. PMID: 15745528

24 Deguchi Y, Shimada K, Nara S, Esaki M, Sakamoto Y, Kosuge T, et al. Pancreaticojejunostomy with invagination of the punched pancreatic remnant after medial pancreatectomy and enucleation for multiple metastases of renal cell carcinoma: report of a case. Surg Today 2009;39:1086-1090. PMID: 19997808

25 DeWitt J, Jowell P, Leblanc J, McHenry L, McGreevy K, Cramer H, et al. EUS-guided FNA of pancreatic metastases: a multicenter experience. Gastrointest Endosc 2005;61:689-696. PMID: 15855973

26 Eidt S, Jergas M, Schmidt R, Siedek M. Metastasis to the pancreas--an indication for pancreatic resection? Langenbecks Arch Surg 2007;392:539-542. PMID: 17242893

27 Fukui S, Nakai Y, Matsumoto Y, Kagebayashi Y, Ko S, Samma S. Solitary metastasis to the pancreas of renal cell carcinoma : a case report. Hinyokika Kiyo 2013;59:729-732. PMID: 24322411

28 Goto T, Dohmen T, Yoneyama K. Pancreatic metastasis from renal cell carcinoma. Clin Gastroenterol Hepatol 2007;5:A26. PMID: 17618839

29 Giulini SM, Portolani N, Bonardelli S, Baiocchi GL, Zampatti M, Coniglio A, et al. Distal pancreatic resection with splenic preservation for metastasis of renal carcinoma diagnosed 24 years later from the nephrectomy. Ann Ital Chir 2003;74:93-96. PMID: 12870287

30 Hata T, Sakata N, Aoki T, Yoshida H, Kanno A, Fujishima F, et al. Repeated pancreatectomy for metachronous duodenal and pancreatic metastases of renal cell carcinoma. Case Rep Gastroenterol 2013;7:442-448. PMID: 24403883

31 Hernandez DJ, Kavoussi LR, Ellison LM. Laparoscopic distal pancreatectomy for metastatic renal cell carcinoma. Urology 2003;62:551. PMID: 12946773

32 Hijioka S, Hifumi M, Mekky MA, Takekuma Y, Kawaguchi T, Yokomizo H, et al. Total pancreatectomy for metastatic renal cell carcinoma with marked extension into the main pancreatic duct. Intern Med 2010;49:557-562. PMID: 20228590

33 Ikari N, Miura O, Takeo S, Okamoto F, Okazaki Y, Nishikawa J, et al. Pancreatic and gastric metastases occurring a decade after nephrectomy for renal cell carcinoma. Nihon Shokakibyo Gakkai Zasshi 2014;111:311-317. PMID: 24500321

34 Irigoin RR, Entrenas AO, Urbano VA, Marín JG, Salgado TP, Zabal JM, et al. Solitary pancreatic metastasis from renal carcinoma. Gastroenterol Hepatol 2011;34:624-628. PMID: 21924525

35 Katsourakis A, Noussios G, Hadjis I, Alatsakis M, Chatzitheoklitos E. Late solitary pancreatic metastasis from renal cell carcinoma: a case report. Case Rep Med 2012;2012:464808. PMID: 22792114

36 Kawakami H, Kuwatani M, Yamato H, Shinada K, Hirano S, Kondo S, et al. Pancreatic metastasis from renal cell carcinoma with intraportal tumor thrombus. Intern Med 2008;47:1967-1970. PMID: 19015609

37 Kijvikai K, Ratana-olarn K. Solitary pancreatic metastasis from renal cell carcinoma 14 years after nephrectomy: a case report. J Med Assoc Thai 2004;87:1123-1126. PMID: 15516017

38 Kitasato A, Tajima Y, Kuroki T, Tsutsumi R, Tsuneoka N, Adachi T, et al. Limited pancreatectomy for metastatic pancreatic tumors from renal cell carcinoma. Hepatogastroenterology 2010;57:354-357. PMID: 20583442

39 Kobayashi A, Yamaguchi T, Ishihara T, Tadenuma H, Nakamura K, Ohshima T, et al. Spontaneous rupture of pancreatic metastasis from renal cell carcinoma. Jpn J Clin Oncol 2004;34:696-699. PMID: 15613561

40 Koide N, Yokoyama Y, Oda K, Nishio H, Ebata T, Abe T, et al. Pancreatic metastasis from renal cell carcinoma: results of the surgical management and pathologic findings. Pancreas 2008;37:104-107. PMID: 18580454

41 Law CH, Wei AC, Hanna SS, Al-Zahrani M, Taylor BR, Greig PD, et al. Pancreatic resection for metastatic renal cell carcinoma: presentation, treatment, and outcome. Ann Surg Oncol 2003;10:922-926. PMID: 14527912

42 Machado NO, Chopra P. Pancreatic metastasis from renal carcinoma managed by Whipple resection. A case report and literature review of metastatic pattern, surgical management and outcome. JOP 2009;10:413-418. PMID: 19581746

43 Maeda H, Okabayashi T, Nishimori I, Kobayashi M, Sugimoto T, Kohsaki T, et al. Duodenum-preserving pancreatic head resection for pancreatic metastasis from renal cell carcinoma: a case report. Langenbecks Arch Surg 2007;392:649-652. PMID: 17605035

44 Masago T, Watanabe T, Nemoto R. Small renal cell carcinoma with pancreas metastasis: a case report. Hinyokika Kiyo 2011;57:607-610. PMID: 22166822

45 Masetti M, Zanini N, Martuzzi F, Fabbri C, Mastrangelo L, Landolfo G, et al. Analysis of prognostic factors in metastatic tumors of the pancreas: a single-center experience and review of the literature. Pancreas 2010;39:135-143. PMID: 19820422

46 Matheiowetz P, Siegel E, Faller G. Jaundice and pancreatic mass: typical clinical presentation of a rare disease. Dtsch Med Wochenschr 2012;137:74-77. PMID: 22241445

47 Matsutani T, Sasajima K, Miyamoto M, Yokoyama T, Maruyama H, Yanagi K, et al. Resection of pancreatic metastasis from renal cell carcinoma and an early gastric cancer. J Nippon Med Sch 2008;75:41-45. PMID: 18360079

48 Mechó S, Quiroga S, Cuéllar H, Sebastià C. Pancreatic metastasis of renal cell carcinoma: multidetector CT findings. Abdom Imaging 2009;34:385-389. PMID: 18404285

49 Medioni J, Choueiri TK, Zinzindohoué F, Cho D, Fournier L, Oudard S. Response of renal cell carcinoma pancreatic metastasis to sunitinib treatment: a retrospective analysis. J Urol 2009;181:2470-2475. PMID: 19371877

50 Minni F, Casadei R, Perenze B, Greco VM, Marrano N, Margiotta A, et al. Pancreatic metastases: observations of three cases and review of the literature. Pancreatology 2004;4:509-520. PMID: 15316227

51 Nagai T, Igase M, Ochi M, Nagai A, Takada K, Kohara K, et al. Multiple metastases from renal carcinoma 15 years after nephrectomy. Nihon Ronen Igakkai Zasshi 2007;44:747-751. PMID: 18198458

52 Nakagohri T, Konishi M, Inoue K, Nakamura T, Kinoshita T. Partial pancreatic head resection for pancreatic metastasis from renal cell carcinoma. Hepatogastroenterology 2003;50: 2236-2238. PMID: 14696506

53 Nakanishi T, Kawamoto H, Fukatsu H, Ishida E, Ogawa T, Okamoto Y, et al. A case of resected pancreatic metastasis from renal cell carcinoma 26 years after right nephrectomy. Nihon Shokakibyo Gakkai Zasshi 2006;103:52-56. PMID: 16444986

54 Ninan S, Jain PK, Paul A, Menon KV. Synchronous pancreatic metastases from asymptomatic renal cell carcinoma. JOP 2005;6:26-28. PMID: 15650281

55 Paparel P, Cotton F, Voiglio E, Decaussin M, Isaac S, Caillot JL. A case of late pancreatic metastasis from renal cell carcinoma. Prog Urol 2004;14:403-405. PMID: 15373187

56 Pekmezci S, Saribeyo?lu K, Kahya AS, Kapan M, Durgun V. Pancreatic renal cell carcinoma metastasis presenting with upper gastrointestinal bleeding. Surgery 2005;137:386-387. PMID: 15746799

57 Riviello C, Tanini I, Cipriani G, Pantaleo P, Nozzoli C, Poma A, et al. Unusual gastric and pancreatic metastatic renal cell carcinoma presentation 10 years after surgery and immunotherapy: A case report and a review of literature. World J Gastroenterol 2006;12:5234-5236. PMID: 16937540

58 Saito J, Yamanaka K, Sato M, Mori N, Sekii K, Yoshioka T, et al. Four cases of advanced renal cell carcinoma with pancreatic metastasis successfully treated with radiation therapy. Int J Clin Oncol 2009;14:258-261. PMID: 19593620

59 Schauer M, Vogelsang H, Siewert JR. Pancreatic resection for metastatic renal cell carcinoma: a single center experience and review of the literature. Anticancer Res 2008;28:361-365. PMID: 18383870

60 Segawa N, Azuma H, Nakanishi Y, Hiraike Y, Kanehara H, Tsuji M, et al. Pancreatic and duodenal metastases from renal cell carcinoma 13 years after radical nephrectomy: a case report. Hinyokika Kiyo 2006;52:845-850. PMID: 17176866

61 Shrikhande SV, Büchler P, Esposito I, Loos M, Büchler MW, Friess H. Splenic and portal vein thrombosis in pancreatic metastasis from renal cell carcinoma. World J Surg Oncol 2006;4:25. PMID: 16704739

62 Sperti C, Pasquali C, Liessi G, Pinciroli L, Decet G, Pedrazzoli S. Pancreatic resection for metastatic tumors to the pancreas. J Surg Oncol 2003;83:161-166. PMID: 12827684

63 Sweeney AD, Wu MF, Hilsenbeck SG, Brunicardi FC, Fisher WE. Value of pancreatic resection for cancer metastatic to the pancreas. J Surg Res 2009;156:189-198. PMID: 19375718

64 Szabó KG, Szentkereszty Z, Tóth LA, Damjanovich L, Sápy P. Distal pancreas resection for metastasis of clear cell renal cancer. Magy Seb 2010;63:161-163. PMID: 20724240

65 Thadani A, Pais S, Savino J. Metastasis of renal cell carcinoma to the pancreas 13 years postnenhrectomv. Gastroenterol Hepatol (N Y) 2011;7:697-699. PMID: 22298966

66 Tuech JJ, Lefebure B, Bridoux V, Albouy B, Lermite E, Le Pessot F, et al. Combined resection of the pancreas and inferior vena cava for pancreatic metastasis from renal cell carcinoma. J Gastrointest Surg 2008;12:612-615. PMID: 17805935

67 Uemura T, Kurita A, Nishimura R, Ishizaki M, Takashima S. Solitary pancreatic metastasis from renal cell carcinoma concomitant with early gastric cancer 17 years after nephrectomy: report of a case. Surg Today 2003;33:395-398. PMID: 12734740

68 Vujcic T, Brahm J, Buckel E, Ibarra A, Vial MT, Fernández M. Pancreatic metastasis from renal cell carcinoma: a case report. Rev Med Chil 2010;138:738-741. PMID: 20919484

69 Watanabe T, Morinaga S, Numata M, Mikayama Y, Tamura S, Tamagawa H, et al. Pancreatic resection for metastatic tumors to the pancreas. Gan To Kagaku Ryoho 2011;38:2068-2070. PMID: 22202286

70 Wente MN, Kleeff J, Esposito I, Hartel M, Müller MW, Fröhlich BE, et al. Renal cancer cell metastasis into the pancreas: a single-center experience and overview of the literature. Pancreas 2005;30:218-222. PMID: 15782097

71 Yabe N, Murai S, Shimizu H, Kitasato K, Yoshikawa T, Oto I, et al. A case of pancreatic metastasis from renal cell carcinoma 27 years after nephrectomy. Gan To Kagaku Ryoho 2013;40:1897- 1899. PMID: 24393958

72 Yokonishi T, Ito Y, Osaka K, Komiya A, Kobayashi K, Sakai N, et al. Pancreatic metastasis from renal cell carcinoma 25 years after radical nephrectomy. Hinyokika Kiyo 2010;56:629-633. PMID: 21187708

73 Yoshikawa Y, Murakami M, Shimizu J, Yasuyama A, Watase C, Kubota M, et al. A case of partial pancreatectomy for recurrent metastatic renal cell carcinoma in the remnant pancreas after subtotal stomach-preserving pancreaticoduodenectomy. Gan To Kagaku Ryoho 2013;40:1900-1902. PMID: 24393959

74 You DD, Choi DW, Choi SH, Heo JS, Kim WS, Ho CY, et al. Surgical resection of metastasis to the pancreas. J Korean Surg Soc 2011;80:278-282. PMID: 22066048

75 Zacharoulis D, Asopa V, Karvounis E, Williamson RC. Resection of renal metastases to the pancreas: a surgical challenge. HPB (Oxford) 2003;5:137-141. PMID: 18332973

76 Zygulska AL, Wójcik A, Richter P, Krzesiwo K. Renal carcinoma metachronous metastases to the gall-bladder and pancreas--case report. Pol Przegl Chir 2012;84:313-316. PMID: 22842744

77 Pantuck AJ, Zisman A, Belldegrun AS. The changing natural history of renal cell carcinoma. J Urol 2001;166:1611-1623. PMID: 11586189

78 Janzen NK, Kim HL, Figlin RA, Belldegrun AS. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am 2003;30:843-852. PMID: 14680319

79 Thompson LD, Heffess CS. Renal cell carcinoma to the pancreas in surgical pathology material. Cancer 2000;89:1076-1088. PMID: 10964338

80 Tsitouridis I, Diamantopoulou A, Michaelides M, Arvanity M, Papaioannou S. Pancreatic metastases: CT and MRI findings. Diagn Interv Radiol 2010;16:45-51. PMID: 20027546

81 Kalra S, Atkinson BJ, Matrana MR, Matin SF, Wood CG, Karam JA, et al. Prognosis of patients with metastatic renal cell carcinoma and pancreatic metastases. BJU Int 2015. PMID: 26032863

82 Santoni M, Conti A, Porta C, Procopio G, Sternberg CN, Basso U, et al. Sunitinib, pazopanib or sorafenib for the treatment of patients with late relapsing metastatic renal cell carcinoma. J Urol 2015;193:41-47. PMID: 25046616

83 Grassi P, Verzoni E, Mariani L, De Braud F, Coppa J, Mazzaferro V, et al. Prognostic role of pancreatic metastases from renal cell carcinoma: results from an Italian center. Clin Genitourin Cancer 2013;11:484-488. PMID: 23791435

84 Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999;17:2530- 2540. PMID: 10561319

85 Mekhail TM, Abou-Jawde RM, Boumerhi G, Malhi S, Wood L, Elson P, et al. Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 2005;23:832-841. PMID: 15681528