Your browser does not fully support modern features. Please upgrade for a smoother experience.
Pancreatic Metastases in Renal Carcinoma: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Oncology
Contributor: Franz Sellner , Sabine Thalhammer

In metastatic renal cell carcinoma, pancreatic metastases can appear in two clinical manifestations: (a) very rarely as isolated pancreatic metastases and (b) in the context with multi-organ metastatic disease. Both courses are characterised by rare, unusual clinical features.

  • renal cell carcinoma metastases
  • isolated pancreatic metastases
  • risk factors
  • tumour evolution
  • seed and soil mechanism

1. Introduction

Metastatic cancer to the pancreas from other primary sites is rare. In autopsy studies, the frequency is estimated at 1.6–11% [1][2][3][4]. Of 16,614 pancreatic operations due to malignancy listed in 16 clinical reports [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], only 258 were performed for pancreatic metastases (PM), resulting in a frequency of just 1.6%. Renal cell carcinoma (RCC), lung carcinomas, colorectal malignancies, melanomas, and sarcomas were reported as the most common primary malignancies [1][2][7][21][22][23][24]. With a proportion of over 60%, RCC is by far the most common primary tumour leading to PM [1][7][14][16][21][22][24][25][26][27], with PM being more frequent in the clear-cell subtype [28]. In the course of metastatic RCC (mRCC), PM may appear: (a) as the sole metastatic site:isolated pancreatic metastasis of RCC (isPMRCC) and (b) in the context with multi-organ metastatic disease.

2. IsPMRCC and the Impact of Prognostic Factors on OS

In older literature there are reports that with synchronous and especially multiple isPMRCC a surgical therapy is not meaningful, since these—analogous to the experience with other solid tumours—were regarded as a negative prognosis criterion with a poor overall survival (OS) [29][30][31][32][33]. In a literature compilation in 2006 [34], our working group demonstrated, however, that the treatment results are not influenced by the singular or multiple or by the synchronous or metachronous occurrence of the PM. The current literature search revealed 12 large (n > 20) institutional reports and compilations [8][13][16][25][35][36][37][38][39][40][41][42] in which data on the impact of clinical risk factors on the OS of operated isPMRCC were presented (Table 2). (The institutional reports were all retrospective and spanned multi-year periods (15–37 years). All studies were performed in surgical departments and inclusion criteria were uniformly surgically treated isPMRCC. Information on the histological subtype was given in four papers: a total of 144 clear cell tumours were compared with only three papillary and one chromophobe. Detailed gene expression analysis and mutation profiles have not yet been presented in isPMRCC).

Table 2. isPMRCC—Impact of potential risk factors for overall survival (OS) after pancreatic surgery; (n = number of patients; Sing/Mult = singular vs. multiple pancreatic metastases (PM), Syn/Metachr = synchronous vs. metachronous; DFI = disease-free interval between RCC and PM surgery; Peripancr. LN = peripancreatic lymph nodes; n.s. = non-significant; p = p-value).

 
Authors Year n Sing/Mult Size Syn/Metachr DFI Peripancr. LN
Institutions reports              
Milanetto [37] 2020 36 n.s.; p 0.61 n.s.; p 0.30 p 0.01 n.s.; p 0.96 p 0.005
Di Franco [36] 2020 21 n.s.; p 0.391 n.s.; p 0.569   n.s.; p 0.143 n.s.; p 0.07
Anderson [25] 2019 29 n.s.        
Benhaim [8] 2015 20 n.s.        
Schwarz [39] 2014 62 n.s.; p 0.9     n.s.; p 0.73 p 0.009
Tosoian [40] 2014 42 n.s.; p 0.727 n.s.; p 0.602 n.s.; p 0.509 n.s.; p 0.738 n.s.; p 0.085
Konstantinidis [13] 2010 20 n.s.; p 0.87 n.s.; p 0.87      
Reddy [16] 2008 21   n.s.; p 0.13 n.s.; p 0.98   p 0.01
Literature compilations              
Sellner [35] 2020 527 n.s.; p 0.350 n.s.; p 0.423 n.s.; p 0.790 n.s.; p 0.786  
Dong [38] 2016 193 n.s.; p 0.67 n.s.; p 0.87 n.s.; p 0.91 n.s.; p 0.53 p 0.03
Masetti [42] 2010 157 n.s.; p 0.862   n.s.; p 0.092 p 0.017  
Tanis [41] 2009 311 n.s.; p 0.892 n.s.; p 0.894 n.s.; p 0.528 n.s.; p 0.528 n.s.; p 0.85

The influence of single vs. multiple PM on the OS was calculated in 11 studies, all of which yielded a negative result. The influence of tumour size was documented in eight publications, all of which were also negative; the disease-free interval (DFI) between RCC and PM surgery was analysed eight times, with one exception always with a negative result. Finally, the influence of synchronous vs. metachronous PM was investigated in seven papers, six of which yielded a negative result. Of a total of 34 analyses investigating the influence of clinical risk factors such as multiple PM, size, synchronous PM, and DFI, 94.1% thus produced a negative result. The analysis of peripancreatic lymph node involvement revealed a contrary result. Investigated in seven publications, an impact on the OS was identified four times. These LN metastases apparently indicate the beginning of the transition from isPMRCC to multiple organ site metastases with poor prognosis in a relevant proportion of observations. Finally, a possible influence of staging and grading of the primary tumour has been investigated so far only by Di Franco [36], who reported a lack of influence. A study of the influence of the IMDC score [43] or molecular markers in isPMRCC was not found in the cited works.

In summary, this confirms that clinical prognostic factors that reflect tumour burden and tumour growth rate, such as size, occurrence of multiple metastases, DFI, or synchronous occurrence of PM, which are generally relevant in metastasis surgery of solid carcinomas [44][45][46], remain ineffective with isPMRCC. In particular, the complete lack of influence of the tumour volume on survival contradicts a general concept of cancer, in which a greater tumour burden of the body results in a poorer outcome [47].

3. Pancreatic Metastases and OS in Multi-Organ Metastatic RCC

In early studies, PM in multi-organ metastases of RCC were often classified as terminal events, with poor forecast due to the lack of an effective drug therapy [48]. Only advances in the drug therapy of the RCC—the introduction in clinical praxis of targeted therapies with antiangiogenetic agents and immunotherapy [49][50][51]—have increasingly sparked interest in the actual frequency, the course, and the clinical relevance of these PM and initiated further investigations. The results (Table 3) unexpectedly show that patients with multi-organ site mRCC and concomitant PM have more favourable survival times than those without PM [52][53][54][47][51]. (The design of the five studies was retrospective four times and was unspecified once. The inclusion criteria were three times a first line anti-angiogenetic therapy, once all PM diagnosed in the observation period, and once were not specified. Detailed genetic and molecular markers analyses have only been reported once [53]).

Table 3. Site metastatic RCC with and without PM and survival; (N = size of the PM group; n = number of metastatic organ sites in the PM group and in control (non-PM) group).

 
Author, Year N Number (n) of Affected Organs and Frequency
(%)		 Median Survival (Months)
Control vs. PM Group
n Control Group PM Group Significance
Singla [53], 2020 31       35 vs. 101
          p < 0.001
Chrom [47], 2018 34 1–2 52% 38% 23 vs. 46
    3, >3 48% 62% p = 0.022
Kalra [51], 2016 44 1 31% 9% 26 vs. 39
    2 40% 23% p < 0.01
    3, >3 29% 68%  
Yuasa [54], 2015 20       p < 0.0001
Grassi [52], 2013 24 1 37% 25% 23 vs. 39
    2 35% 21% p = 0.0004
    3, >3 28% 54%

In 2013, Grassi [52] reported for the first time that in mRCC the median OS was more favourable for patients with PM at 39 months than for those without PM at 23 months (p = 0.0004), an observation made by Yuasa [54] in 2015 reaffirmed. Kalra [51] confirmed this result in a comprehensive study again in 2016: a median OS of 39 months for patients with PM corresponded to 26 months for patients without PM (p < 0.01), although the total number of affected organs was greater in the collective with PM (p < 0.001). Chrom [47] also observed a better OS for the group of mRCC with pancreatic involvement: 46 months vs. 23 months, which was significant in univariate analysis (p = 0.022) but did not prove to be an independent variable in multivariate analysis. In a recent study, Singla [53] compared mRCC with and without presence of PM with regard to clinical behaviour and underlying biology. In doing so it was reaffirmed that the cohort with PM had a more favourable OS than the one without PM (OS 101 vs. 35 months (p < 0.001), 5-year survival rates 88% vs. 31%, p < 0.001). There was also a high sensitivity of the cohort with PM to antiangiogenetic agents with a disease-free survival of 26.9 vs. 8.3 months (p = 0.007) and a simultaneous resistance to immune checkpoint inhibitors with more rapid progress of PM observations (p = 0.034). Finally, within the PM cohort, Singla noted an independence (p = 0.684) of survival from the established IMDC score, which is not based on pathological–anatomical parameters. This observation, however, is in contrast to Yuasa [54], who observed in the PM group a significant difference in OS between good and intermediate IMDC risk patients (p = 0. 013). As a summary, all five investigations carried out so far consistently show that the presence of PM exerts a positive influence on the OS in mRCC.

However, in the three publications [52][47][51] (Table 3) that reported on the possible influence of the number of organs affected by metastases, it was consistently shown that the proportion of single organ metastases was smaller in mRCC with PM than in the respective non-PM control group, and vice versa, the rate of observations with three or more affected organs in the PM group was higher than in the control group. The cohorts with PM were thus consistently characterised by a reduced proportion of prognostically favourable single organ metastases and an increased proportion of prognostically unfavourable multi-organ metastases. In the study of Kalra [51], the difference even reached significance level (p < 0.001). Thus, the paradox is that in the mRCC, the presence of PM is associated with more favourable OS, although the total number of affected metastatic organ sites is greater. Therefore, an unconscious selection bias of favourable cases with lower number of metastatic organ sites in the PM group has to be excluded as the cause of the more favourable prognosis. The better prognosis, despite the higher rate of affected organs in the PM group, indicates that the occurrence of PM in the mRCC is associated with tumour cell properties, which trigger a more favourable course [52][53][51].

4. Conclusions

The occurrence of PM in metastatic RCC—both isPMRCC and PM in multiple organ site mRCC—is coupled to clinical features that differ in some aspects from those common in solid tumour metastases, e.g., the possibility of isolated occurrence (isPMRCC), ineffectiveness of volume and growth-rate related risk factors, and better prognosis despite a larger number of affected organs. In the case of isPMRCC in particular, three special features can be detected that differ from the behaviour generally observed in extrapancreatic metastases of mRCC: (1) Genetic alterations associated with lower tumour aggressiveness; (2) The lack of influence of tumour volume and growth rate dependent prognostic factors; and (3) Immunotherapy, which is very effective in mRCC, remains ineffective in isPMRCC. Of course, it is conceivable that these three properties are completely independent of each other. However, this leads to the unsatisfactory explanation that these embolised RCC cells are equipped with an accumulation of unusual biological properties. The data presented, however, can just as well be explained by the coincidence of special RCC cells with a postulated highly specific SSM in isPMRCC. At the beginning of the process there is undoubtedly the evolution of tumour cells that leads to a multiplicity of different cell species with different cell genomes (according to the cancer evolutionary model, this cell diversity is the result of a phase of genome chaos [55][56][57][58] with following genome re-organisation [59][60][58], which is responsible not only for a diversity of cell genomes, but also for possible chromosomal rearrangements that are associated with drug resistance [56][61], drawing attention to the concept of adaptative therapy [59][56][62]). It is a specificity of the isPMRCC entity that those few circulating tumour cells that eventually settle and develop into manifest metastases are linked with reduced aggressiveness, as evidenced by genetic studies as well as the clinically proven slow progression of the disease. However, the reduced aggressiveness by itself cannot explain the phenomenon of isolated occurrence of PM and the lack of influence of risk factors. According to current knowledge, an organotropism in metastasis development—and one such is undoubtedly the isolated occurrence of PM in mRCC—is linked to a SSM. Therefore, the exclusive occurrence of metastases in one organ (pancreas) presupposes that these cells, during their evolution, are endowed not only with a low aggressiveness but also with additional properties that can trigger a highly selective SSM in host organs. This favours metastasis settlement in individual organs and prevents it in others. Therefore, in isPMRCC too, the clinical behaviour is the common end product of tumour and host biology [63].

Which biochemical alterations of the tumour cells and/or of the host organs trigger such a SSM in isPMRCC is currently unknown and reserved for future investigations. Though isolated PM of the RCC are very rare, they deserve increased investigations as there are indications that clinical course is determined—in addition to genetic changes— to an unusually high degree by a SSM too. An elucidation of the biochemical changes that control this SSM could lead to a deeper understanding of the processes that promote or prevent the colonisation of metastatic tumour cells.

This entry is adapted from the peer-reviewed paper 10.3390/cancers13061342

References

  1. Yagi, T.; Hashimoto, D.; Taki, K.; Yamamura, K.; Chikamoto, A.; Ohmuraya, M.; Beppu, T.; Baba, H. Surgery for metastatic tumors to the pancreas. Surg. Case Rep. 2017, 3, 31.
  2. Untch, B.R.; Allen, P.J. Pancreatic metastasectomy: The Memorial Sloan-Kettering experience and a review of the literature. J. Surg. Oncol. 2014, 109, 28–30.
  3. Ballarin, R.; Spaggiari, M.; Cautero, N.; De Ruvo, N.; Montalti, R.; Longo, C.; Pecchi, A.; Giacobazzi, P.; De Marco, G.; D’Amico, G.; et al. Pancreatic metastases from renal cell carcinoma: The state of the art. World J. Gastroenterol. 2011, 17, 4747–4756.
  4. Adsay, V.N.; Andea, A.; Basturk, O.; Kilinc, N.; Nassar, H.; Cheng, J.D. Secondary tumors of the pancreas: An analysis of a surgical and autopsy database and review of the literature. Virchows Arch. 2004, 444, 527–535.
  5. Fahlbusch, T.; Luu, A.M.; Braumann, C.; Lukas, C.; Uhl, W.; Künzli, B.M. Lipomatous pancreas facilitates late onset of renal cell carcinoma metastases. Acta Chir. Belg. 2020, 18, 1–6.
  6. Chikhladze, S.; Lederer, A.K.; Kühlbrey, C.M.; Hipp, J.; Sick, O.; Fichtner-Feigl, S.; Wittel, U.A. Curative-intent pancreas resection for pancreatic metastases: Surgical and oncological results. Clin. Exp. Metastasis 2020, 37, 313–324.
  7. Endo, Y.; Noda, H.; Watanabe, F.; Kato, T.; Kakizawa, N.; Ichida, K.; Kasahara, N.; Rikiyama, T. A retrospective analysis of preoperative evaluation and surgical resection for metastatic tumors of the pancreas. Indian J. Surg. Oncol. 2019, 10, 251–257.
  8. Benhaim, R.; Oussoultzoglou, E.; Saeedi, Y.; Mouracade, P.; Bachellier, P.; Lang, H. Pancreatic metastasis from clear cell renal cell carcinoma: Outcome of an aggressive approach. Urology 2015, 85, 135–140.
  9. Wiltberger, G.; Bucher, J.N.; Krenzien, F.; Benzing, C.; Atanasov, G.; Schmelzle, M.; Hau, H.M.; Bartels, M. Extended resection in pancreatic metastases: Feasibility, frequency, and long-term outcome: A retrospective analysis. BMC Surg. 2015, 15, 126.
  10. Kimura, Y.; Keira, Y.; Imamura, M.; Ito, T.; Nobuoka, T.; Mizuguchi, T.; Masumori, N.; Hasegawa, T.; Hirata, K. Histopathological aspects of pancreatic metastases in renal cell carcinoma: Does the mode of invasion permit limited resections? Pancreat. Disord. Ther. 2014, 4, 2.
  11. Moletta, L.; Milanetto, A.C.; Vincenzi, V.; Alaggio, R.; Pedrazzoli, S.; Pasquali, C. Pancreatic secondary lesions from renal cell carcinoma. World J. Surg. 2014, 38, 3002–3006.
  12. You, D.D.; Choi, D.W.; Choi, S.H.; Heo, J.S.; Kim, W.S.; Ho, C.Y.; Lee, H.G. Surgical resection of metastasis to the pancreas. J. Korean Surg. Soc. 2011, 80, 278–282.
  13. Konstantinidis, I.T.; Dursun, A.; Zheng, H.; Wargo, J.A.; Thayer, S.P.; Fernandez-del Castillo, C.; Warshaw, A.L.; Ferrone, C.R. Metastatic tumors in the pancreas in the modern era. J. Am. Coll. Surg. 2010, 211, 749–753.
  14. Mourra, N.; Arrive, L.; Balladur, P.; Flejou, J.F.; Tiret, E.; Paye, F. Isolated metastatic tumors to the pancreas. Hôpital St-Antoine experience. Pancreas 2010, 39, 577–580.
  15. Koide, N.; Yokoyama, Y.; Oda, K.; Nishio, H.; Ebata, T.; Abe, T.; Igami, T.; Nimura, Y.; Nagino, M. Pancreatic metastasis from renal cell carcinoma. Results of the surgical management and pathologic findings. Pancreas 2008, 37, 104–107.
  16. Reddy, S.; Edil, B.H.; Cameron, J.L.; Pawlik, T.M.; Herman, J.M.; Gilson, M.M.; Campbell, K.A.; Schulick, R.D.; Ahuja, N.; Wolfgang, C.L. Pancreatic resection of isolated metastases from nonpancreatic primary cancers. Ann. Surg. Oncol. 2008, 15, 3199–3206.
  17. Schauer, M.; Vogelsang, H.; Siewert, J.R. Pancreatic resection for metastatic renal cell carcinoma: A single center experience and review of the literature. Anticancer Res. 2008, 28, 361–366.
  18. Akatsu, T.; Shimazu, M.; Aiura, K.; Ito, Y.; Shinoda, M.; Kawachi, S.; Tanabe, M.; Ueda, M.; Kitajima, M.; Kitagawa, Y. Clinicopathological features and surgical outcome of isolated metastasis of renal cell carcinoma. Hepatogastroenterology 2007, 54, 1836–1840.
  19. Wente, M.N.; Kleeff, J.; Esposito, I.; Hartel, M.; Müller, M.W.; Fröhlich, B.E.; Büchler, M.W.; Friess, H. Renal cancer cell metastasis into the pancreas. A single-center experience and overview of the literature. Pancreas 2005, 30, 218–222.
  20. Faure, J.P.; Tuech, J.J.; Richer, J.P.; Pessaux, P.; Arnaud, J.P.; Carretier, M. Pancreatic metastasis of renal cell carcinoma: Presentation, treatment and survival. J. Urol. 2001, 165, 20–22.
  21. Madkhali, A.A.; Shin, S.; Song, K.B.; Lee, J.H.; Hwang, D.W.; Park, K.M.; Lee, Y.J.; Kim, S.C. Pancreatectomy for secondary metastasis of the pancreas: A single-institution experience. Medicine 2018, 97, e12653.
  22. Alzahrani, M.A.; Schmulewitz, N.; Grewal, S.; Lucas, F.V.; Turner, K.O.; McKenzie, J.T.; Sussman, J.J.; Ahmad, S.A. Metastases to the pancreas: The experience of a high volume center and a review of the literature. J. Surg. Oncol. 2012, 105, 156–161.
  23. Sperti, C.; Moletta, L.; Patanè, G. Metastatic tumors to the pancreas: The role of surgery. World J. Gastrointest. Oncol. 2014, 15, 381–392.
  24. Ito, T.; Takada, R.; Omoto, S.; Tsuda, M.; Masuda, D.; Kato, H.; Matsumoto, T.; Moriyama, I.; Okabe, Y.; Shiomi, H.; et al. Analysis of prognostic factors in pancreatic metastasis: A multicentre retrospective analysis. Pancreas 2018, 47, 1033–1039.
  25. Anderson, B.; Williams, G.A.; Sanford, D.E.; Liu, J.; Dageforde, L.A.; Hammill, C.W.; Fields, R.C.; Hawkins, W.G.; Strasberg, S.M.; Doyle, M.B.; et al. A 22-year experience with pancreatic resection for metastatic renal cell carcinoma. HPB 2020, 22, 312–317.
  26. Sweeney, A.D.; Fisher, W.E.; Wu, M.F.; Hilsenbeck, S.G.; Brunicardi, C.F. Value of pancreatic resection for cancer metastatic to the pancreas. J. Surg. Res. 2010, 160, 268–276.
  27. Strobel, O.; Hackert, T.; Hartwig, W.; Bergmann, F.; Hinz, U.; Wente, M.N.; Fritz, S.; Schneider, L.; Büchler, M.W.; Werner, J. Survival data justifies resection for pancreatic metastases. Ann. Surg. Oncol. 2009, 16, 3340–3349.
  28. Dudani, S.; de Velasco, G.; Wells, C.; Gan, C.L.; Donskov, F.; Porta, C.; Fraccon, A.; Pasini, F.; Lee, J.L.; Hansen, A.R.; et al. Characterizing sites of metastatic involvement in metastatic clear-cell, papillary, and chromophobe renal cell carcinoma. J. Clin. Oncol. 2020, 38, 5071.
  29. Béchade, D.; Palazzo, I.; Desramé, J.; Duvic, C.; Hérody, M.; Didelot, F.; Coutant, G.; Algayres, J. Pancreatic metastasis of renal carcinoma: Report of three cases. Rev. Med. Interne 2002, 23, 862–866.
  30. Espinoza, E.; Hassani, A.; Vaishampayan, U.; Shi, D.; Pontes, J.E.; Weaver, D.W. Surgical excision of duodenal/pancreatic metastatic renal cell carcinoma. Front. Oncol. 2014, 4, 218.
  31. 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.
  32. Mehta, N.; Volpe, C.; Haley, T.; Balos, L.; Bradley, E.L.; Doerr, R.J. Pancreaticoduodenectomy for metastatic renal cell carcinoma: Report of a case. Surg. Today 2000, 30, 94–97.
  33. Eloubeidi, M.A.; Jhala, D.; Chhieng, D.C.; Jhala, N.; Eltoum, I.; Wilcox, C.M. Multiple late asymptomatic pancreatic metastases from renal cell carcinoma: Diagnosis by endoscopic ultrasound-guided fine needle aspiration biopsy with immunocytochemical correlation. Dig. Dis. Sci. 2002, 47, 1839–1842.
  34. 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.
  35. Sellner, F. Isolated pancreatic metastases of renal cell carcinoma—A paradigm of a seed and soil mechanism: A literature analysis of 1034 observations. Front. Oncol. 2020, 10, 709.
  36. Di Franco, G.; Gianardi, D.; Matteo Palmeri, M.; Furbetta, N.; Guadagni, S.; Bianchini, M.; Bonari, F.; Sbrana, A.; Vasile, E.; Pollina, L.E.; et al. Pancreatic resections for metastases: A twenty-year experience from a tertiary care center. Eur. J. Surg. Oncol. 2020, 46, 825–831.
  37. Milanetto, A.C.; Morelli, L.; Di Franco, G.; David, A.; Campra, D.; De Paolis, P.; Pasquali, C. A plea for surgery in pancreatic metastases from renal cell carcinoma: Indications and outcome from a multicenter surgical experience. J. Clin. Med. 2020, 9, 3278.
  38. Dong, J.; Cong, L.; Zhang, T.P.; Zhao, Y.P. Pancreatic metastasis of renal cell carcinoma. Hepatobiliary Pancreat. Dis. Int. 2016, 15, 30–38.
  39. Schwarz, L.; Sauvanet, A.; Regenet, N.; Mabrut, J.Y.; Gigot, J.F.; Housseau, E.; Millat, B.; Ouaissi, M.; Gayet, B.; Fuks, D.; et al. Long-term survival after pancreatic resection for renal cell carcinoma metastasis. Ann. Surg. Oncol. 2014, 21, 4007–4013.
  40. Tosoian, J.J.; Cameron, J.L.; Allaf, M.E.; Hruban, R.H.; Nahime, C.B.; Pawlik, T.M.; Pierorazio, P.M.; Reddy, S.; Wolfgang, C.L. Resection of isolated renal cell carcinoma metastases of the pancreas: Outcomes from the Johns Hopkins Hospital. J. Gastrointest. Surg. 2014, 18, 542–548.
  41. Tanis, P.J.; van der Gaag, N.A.; Busch, O.R.; van Gulik, T.M.; Gouma, D.J. Systematic review of pancreatic surgery for metastatic renal cell carcinoma. Br. J. Surg. 2009, 96, 579–592.
  42. Masetti, M.; Zanini, N.; Martuzzi, F.; Fabbri, C.; Mastrangelo, L.; Landolfo, G.; Fornelli, A.; Burzi, M.; Vezzelli, E.; Jovine, E. Analysis of prognostic factors in metastatic tumors of the pancreas: A single-center experience and review of the literature. Pancreas 2010, 39, 135–143.
  43. Heng, D.Y.; Xie, W.; Regan, M.M.; Warren, M.A.; Golshayan, A.R.; Sahi, C.; Eigl, B.J.; Ruether, J.D.; Cheng, T.; North, S.; et al. Prognostic factors for overall survival in patients with metastatic renal carcinoma treated with vascular endothelial growth factor—Targeted agents: Results from a large, multicenter study. J. Clin. Oncol. 2009, 27, 5794–5799.
  44. Tosco, L.; Van Poppel, H.; Frea, B.; Gregoraci, G.; Joniau, S. Survival and impact of clinical prognostic factors in surgically treated metastatic renal cell carcinoma. Eur. Urol. 2013, 63, 646–652.
  45. Iacovelli, R.; Lanoy, E.; Albiges, L.; Escudier, B. Tumour burden is an independent prognostic factor in metastatic renal cell carcinoma. BJU Int. 2012, 110, 1747–1754.
  46. Dabestani, S.; Marconi, L.; Hofmann, F.; Stewart, F.; Lam, T.B.; Canfield, S.E.; Staehler, M.; Powles, T.; Ljungberg, B.; Bex, A. Local treatments for metastases of renal cell carcinoma: A systematic review. Lancet Oncol. 2014, 15, e549–e561.
  47. Chrom, P.; Stec, R.; Bodnar, L.; Szczylik, C. Prognostic significance of pancreatic metastases from renal cell carcinoma in patients treated with tyrosine kinase inhibitors. Anticancer Res. 2018, 38, 359–365.
  48. Sohn, T.A.; Yeo, C.J.; Cameron, J.L.; Nakeeb, A.; Lillemoe, K.D. Renal cell carcinoma metastatic to the pancreas: Results of surgical management. J. Gastrointest. Surg. 2001, 5, 346–351.
  49. Jonasch, E. Updates to the management of kidney cancers. J. Natl. Compr. Cancer Netw. 2018, 16, 639–641.
  50. Flippot, R.; Escudier, B.; Albiges, L. Immune checkpoint inhibitors: Toward new paradigms in renal cell carcinoma. Drugs 2018, 78, 1443–1457.
  51. Kalra, S.; Atkinson, B.J.; Matrana, M.R.; Matin, S.F.; Wood, C.G.; Karam, J.A.; Tamboli, P.; Sircar, K.; Rao, P.; Corn, P.G.; et al. Prognosis of patients with metastatic renal cell carcinoma and pancreatic metastases. BJU Int. 2016, 117, 761–765.
  52. Grassi, P.; Verzoni, E.; Mariani, L.; De Braud, F.; Coppa, J.; Mazzaferro, V.; Procopio, G. Prognostic role of pancreatic metastases from renal cell carcinoma: Results from an Italian center. Clin. Genitourin. Cancer 2013, 11, 484–488.
  53. Singla, N.; Xie, Z.; Zhang, Z.; Gao, M.; Yousuf, Q.; Onabolu, O.; McKenzie, T.; Tcheuyap, V.T.; Ma, Y.; Choi, J.; et al. Pancreatic tropism of metastatic renal cell carcinoma. JCI Insight 2020, 5, e134564.
  54. Yuasa, T.; Inoshita, N.; Saiura, A.; Yamamoto, S.; Urakami, S.; Masuda, H.; Fujii, Y.; Fukui, I.; Ishikawa, Y.; Yonese, J. Clinical outcome of patients with pancreatic metastases from renal cell cancer. BMC Cancer 2015, 15, 46.
  55. Heng, H.H.; Regan, S.; Ye, C. Genotype, environment, and evolutionary mechanism of diseases. Environ. Dis. 2016, 1, 14–23.
  56. Heng, J.; Heng, H.H. Genome chaos: Creating new genomic information essential for cancer macroevolution. Semin. Cancer Biol. 2020.
  57. Heng, H.H.; Stevens, J.B.; Bremer, S.W.; Liu, G.; Abdallah, B.Y.; Ye, C.J. Evolutionary mechanisms and diversity in cancer. Adv. Cancer Res. 2011, 112, 217–253.
  58. Liu, G.; Stevens, J.B.; Horne, S.D.; Abdallah, B.Y.; Ye, K.J.; Bremer, S.W.; Ye, C.J.; Chen, D.J.; Heng, H.H. Genome chaos: Survival strategy during crisis. Cell Cycle 2014, 13, 528–537.
  59. Ye, C.J.; Sharpe, Z.; Heng, H.H. Origins and consequences of chromosomal instability: From cellular adaptation to genome chaos-mediated system survival. Genes 2020, 11, 1162.
  60. Ye, C.J.; Stilgenbauer, L.; Moy, A.; Liu, G.; Heng, H.H. What is karyotype coding and why is genomic topology important for cancer and evolution? Front. Genet. 2019, 10, 1082.
  61. Pienta, K.J.; Hammarlund, E.U.; Austin, R.H.; Axelrod, R.; Brown, J.S.; Amend, S.R. Cancer cells employ an evolutionarily conserved polyploidization program to resist therapy. Semin. Cancer Biol. 2020.
  62. Gatenby, R.A.; Silva, A.S.; Gillies, R.J.; Frieden, B.R. Adaptive therapy. Cancer Res. 2009, 69, 4894–4903.
  63. Voss, M.H.; Reising, A.; Cheng, Y.; Patel, P.; Marker, M.; Kuo, F.; Chan, T.A.; Choueiri, T.K.; Hsieh, J.J.; Hakimi, A.A.; et al. Genomically annotated risk model for advanced renal-cell carcinoma: A retrospective cohort study. Lancet Oncol. 2018, 19, 1688–1698.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
Academic Video Service
Feedback

Quick Survey

Encyclopedia MDPI is conducting a targeted survey to identify the specific barriers hindering efficient research. We invite you to spend 3 minutes defining the priorities for our next generation of structured knowledge tools.
Take Survey