Frantz's tumor: Is mutilating surgery always justified in young patients?

Surgical Oncology (2011) 20, 121e125

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REVIEW

Frantz’s tumor: Is mutilating surgery always justified in young patients? M. Campanile a,*, A. Nicolas b, S. LeBel c, A. Delarue a, J.M. Guys a, P. de Lagausie a a

Department of Pediatric Surgery, Hoˆpital Timone Enfants, Marseille, France Department of Pediatric Oncology, Hoˆpital Timone Enfants, Marseille, France c Department of Anesthesia and Intensive Care, Hoˆpital Timone Enfants, Marseille, France b

Accepted 16 December 2009

KEYWORDS Frantz’s tumor; Solid-pseudopapillary; Pancreas; Follow up; Recurrence

Abstract Background: Solid pseudopapillary tumor (Frantz’s tumor) of the pancreas is a rare lesion. It is of low-grade malignancy but can cause extensive local invasion. The aim of this study was to assess the outcome of Frantz’s tumors after incomplete resection. Methods: We contacted all authors who published case reports describing incomplete resection of Frantz’s tumor between 1985 and 2008 to request follow-up information. Results: Follow-up information was obtained for 11 out 18 patients who underwent incomplete resection. Estimated median survival rate was 5.7 years (69.5 months). Conclusion: Since Frantz’s tumor typically develops mainly in children and young women, a 5.7 year survival rate is unacceptable. Thus complete resection of locally invasive solidpseudopapillary tumor of the pancreas is always justified, even at the price of difficult, mutilating surgery. ª 2009 Elsevier Ltd. All rights reserved.

* Corresponding author. Department of Pediatric Surgery, Ho ˆpital Timone Enfants, 264 Rue Saint Pierre, 13385 Marseille, France. Tel.: þ33 491386682; fax: þ33 0 491384714. E-mail address: [email protected] (M. Campanile). 0960-7404/$ - see front matter ª 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.suronc.2009.12.003

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Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 Author form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 Contribution author name . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124

Introduction Solid pseudopapillary tumor of the pancreas (Frantz’s tumor) is a rare lesion. It is of low malignant potential, but can produce extensive local invasion. The best treatment is a complete resection without breaking up the lesion and avoiding laparoscopic approach [1]. However, since the doubling time of this tumor appears to be slow (765 days) [2], the question arises as to whether mutilating resection sacrificing organs and/or blood vessels is warranted. We decided to assess this question after observing high postoperative morbidity following treatment of a young girl in our department. The purpose of this report is to describe our patient and a retrospective review of previous cases of incomplete resection for Frantz’s tumor. In order to evaluate long-term risk of this tumor after incomplete resection, we contacted all authors who published case reports describing incomplete resection of Frantz’s tumor between 1985 and 2008 to request follow-up information. Incomplete resection was defined in two categories, i.e., resection microscopically incomplete (R1) and resection macroscopically incomplete (R2).

insufficiency, portal vein thrombosis (cavernoma), and asplenic events (e.g. infection). In view of these postoperative complications, we reviewed our policy for management Frantz’s tumor. For this purpose we carried out a retrospective study to determine the long-term outcome of all publications describing incomplete resection of Frantz’s tumor (Pubmed: Frantz, tumor, solid-pseudopapillary, pancreas) between 1985 and 2008. Incomplete resection was defined as microscopically incomplete resection (R1) and macroscopically incomplete resection (R2). We contacted all authors who reported incomplete resection to request updated follow-up information.

Results We contacted 14 authors (by email, letter, or fax) who reported cases of Frantz’s tumor treated by incomplete resection. One author described 3 cases, two described 2 cases and the other 11 authors described 1 case each.

Methods An 11-year-old girl was admitted to our hospital for vomiting, jaundice and abdominal mass. Radiologic examination demonstrated a voluminous mass (12 cm) developing from the pancreas to contiguous organs. A preoperative biopsy was performed and it was diagnosed as a Frantz’s tumor (Fig. 1). The girl was underwent multiple surgical interventions. Procedures included a cephalic duodeno-pancreatectomy extended to isthmus, partial resection of the superior mesenteric vein, right and transverse colectomy, left hepatic lobectomy and splenectomy for spleen necrosis. Postoperative complications included thrombosis of the portal vein, pancreatic insufficiency, and pancreatic fistula. The total duration of hospitalization was 9 months. With follow-up now standing at 13 months after the first procedure, the patient is currently well, but we speculate that long-term complications could include pancreatic

Figure 1 Abdominal magnetic resonance, axial incidence showing a voluminous, heterogeneous, well encapsulated mass developing from the head of the pancreas in our patient.

Frantz’s tumor

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The total number of cases was 18 including 10 R1 and 8 R2 resections [3e16]. In one case the tumor broke up during resection [13]. Eleven authors responded including 2 who could not access the data, 1 who had lost the patient from follow-up (non compliant patient), and 8 who provided the requested information. Three authors did not respond. Information was obtained for 11 cases including 5 R1 and 6 R2 resections. A total of 8 patients were dead including 1 due to hepatic encephalopathy at 83 months after surgery, 1 due to diabetes at 27 years after surgery, and 6 patients due to recurrent disease at intervals ranging from 4 to 156 months after surgery. The remaining 3 patients were alive and with no recurrence at 7 years after surgery (Table 1). Overall (R1 and R2) median survival was 69.5 months (5.7 years). Median survival was 84 months for patients in the R1 group and 87.5 months for patients in the R2 group. This difference was not statistically significant (p Z 0.43).

Discussion Because of the indolent nature of Frantz’s tumor and high morbidity following aggressive surgery [17,18], the most appropriate surgical approach is still controversial. According to this retrospective study, overall median survival after incomplete resection of Frantz’s tumor reported in the literature was only 5.7 years. There was no statistically significant difference between patients who underwent R1 resection (microscopically incomplete) or R2 resection (macroscopically incomplete). These findings indicate that the long-term prognosis after incomplete resection is poor and support the use of radical resection even at the expense of sacrificing organs and/or Table 1

Follow up of patients incompletely resected.

Patient no

Author

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Cappellari J.O. [3] Carboni F. [4] Goh B.K.P. [5] Goh B.K.P. [5] Horvath K.D. [6] Jeng L.B.B. [7] Martin R.C.G. [8] Martin R.C.G. [8] Matsunou H. [9] Nakagohri T. [10] Nakagohri T. [10] Nakagohri T. [10] Nishihara K. [11] Podevin J. [12] Sclafani L.M. [13] Sto ¨mmer P. [14] Tipton S.G. [15] Zinner M.J. [16]

R1

R2

Follow Up (yr, mo)

X

? DOD (4 mo) ? ? ? DOC (6 yr, 11 mo) DOD (13 yr) DOD (1 yr) DOD (3 yr, 11 mo) AW (7 yr) AW (7 yr) AW (7 yr) DOD (10 yr, 11 mo) ? ? ? DOD (7 yr, 8 mo) DOC (27 yr)

X X X X X X X X X X X X X X X X X

AW: alive and well; DOD: died of disease; DOC: died of another cause; ?: no answer.

blood vessels. This approach is particularly valid for a tumor that occurs especially in young girls. Solid pseudopapillary tumor of the pancreas (Frantz’s tumor) is a rare entity of unknown origin. It accounts for only 1e2% of all exocrine pancreatic tumors [19]. Frantz’s tumor usually occurs in women during the second or third decade of life, with a high prevalence in Asiatic women [20,21]. The tumor has a low malignant potential and tumordoubling time is very slow: 765 days [2]. Nevertheless, malignant cases account for approximately 15% of adult cases [19] and 13% of pediatric cases [22]. Most malignant cases have occurred in males or patients older than thirty years old [23], but it is unpredictable. Malignancy is defined based on histopathological criteria for vascular and perineural infiltration. These criteria include elevated mitotic rate, high degree of cellular polymorphism, presence of metastases, and recurrence [9,11,12,15,19]. However absence of one or more of these features does not rule out malignant behavior [24,25]. Five-year survival after radical resection is 95%, but rapidly fatal cases have been reported [26]. The rate of recurrence after radical resection ranges from 10e15%, mostly involving the liver [19,21,26]. Vascular and local invasion, recurrence or limited metastases are not contraindications for resection; patients with ‘‘unresectable’’ tumors who survived for more than 10 years after surgery have been reported [11,16,19,27,28]. Surgery for pancreatic tumors can be very difficult. To avoid recurrence, it is necessary to achieve margins of at least 3 to 5 mm in healthy tissue. This can require splenectomy, vein cavectomy or partial hepatectomy. Caudal resection including the spleen carries infectious risks. Cephalic resections can necessitate reconstruction of the superior mesenteric vein or artery or pancreatic fistula. Invasion of big vessels, e.g., the inferior vena cava, may necessitate partial vasectomy. Large resections of pancreas can lead to pancreatic insufficiency or diabetes. Laparoscopy seems not to be indicated for the treatment of the solid and pseudo-papillary tumors because of a possible ‘‘spray effect’’ and the consequent risk of peritoneal carcinosis [1]. This is a rare complication that can occur in case of abdominal trauma and tumor’s breaking [29]. Therefore per-operative biopsy, tumor’s breaking and incomplete resection must be avoided. In case of incomplete resection some therapeutic options should be considered. In this regard, the value of chemotherapy, radiotherapy, or chemoembolization as neo- or adjuvant treatment for Frantz’s tumor is still under evaluation although encouraging results have been reported [9,27,30e34]. Careful long-term follow-up is required.

Conclusion Despite the low malignant potential of Frantz’s tumor, the results of our review of the literature show that, median survival in patients who undergo incomplete is only 5.7 years. This is unacceptable for young patients. Complete surgical resection should be performed in patients presenting locally invasive solid-pseudopapillary

124 tumor of the pancreas, even if it requires difficult, mutilating surgery. Further study is needed.

Conflict of interest statement None declared.

Acknowledgments THANKS TO: M Brennan [13], J Cameron [16], F Carboni [4], K Horvath [6], T Nakagohri [10], LLPJ Ooi [5], J Podevin [12], LM Sclafani [13], M Siech [18], GB Thompson [15] for providing their follow-up data.

Author form Surgical Oncology will consider manuscripts which are prepared according to the guidelines adopted by the International Committee of Medical Journal Editors (‘‘Uniform requirements for manuscripts submitted to biomedical journals’’). For more information please visit www.icmje.org. Submission of an article implies that the work described has not been published previously (except in the form of an abstract or as part of a published lecture or academic thesis), that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, without the written consent of the Publisher. Authors are required to identify the contribution(s) for which they are responsible. Article title: Frantz’s tumor: is a mutilating surgery always justified in young patients?

Contribution author name Guarantor of the integrity of the study: De Lagausie Pascal Study concepts: De Lagausie Pascal Study design: Campanile Manuela Definition of intellectual content: Campanile Manuela Literature research: Campanile Manuela Clinical studies: Campanile Manuela, Delarue Arnauld Experimental studies: Data acquisition: Le Bel Stephane Data analysis: Nicolas Andre ´ Statistical analysis: Campanile Manuela Manuscript preparation: Campanile Manuela Manuscript editing: Campanile Manuela Manuscript review: Guys Jean Michel Written permission from the following parties is enclosed with the manuscript: a) those named in the Acknowledgements who have been credited with a scientific contribution to the work, and b) those cited in the manuscript as personal communications.

M. Campanile et al. This form must be signed by the corresponding author on behalf of all authors.

References [1] Fais PO, Carricaburu E, Sarnacki S, Berrebi D, Orbach D, Baudoin V, et al. Is laparoscopic management suitable for solid pseudo-papillary tumors of the pancreas safe? Ped Surg Int 2009;25(7):617e21. [2] Kato T, Egawa N, Kamisura T, Tu Y, Sanaka M, Sakaki N, et al. A case of solid pseudopapillary neoplasm of the pancreas and tumor doubling time. Pancreatology 2002;2:495e8. [3] Cappellari JO, Geisinger KR, Albertson DA, Tolfman NT, Kute TE. Malignant papillary cystic tumor of the pancreas. Cancer 1990;66:193e8. [4] Carboni F, Lepiane P, Santoro R, Lorusso R, Mancini R, Proposito D, et al. Cystic pancreatic neoplasm: 12 year surgical experience. J Exp Clin Cancer Res 2006;25(2): 167e75. [5] Goh BKP, Tan YM, Cheow PC, Chung Y-FA, Chow PKH, Wong W-K, et al. Solid pseudopapillary neoplasm of the pancreas: an updated experience. J Surg Oncol 2007;95:640e4. [6] Horvath KD, Chabot J. An aggressive resectional approach to cystic neoplasm of the pancreas. Am J Surg 1999;178:269e74. [7] Jeng LBB, Chen MF, Tang RP. Solid and papillary neoplasm of the pancreas. Emphasis on surgical treatment. Arch Surg 1993; 128:433e6. [8] Martin RCG, Klimstra DS, Brennan MF, Conlon KC. Solid-pseudopapillary tumor of the pancreas: a surgical enigma? Ann Surg Oncol 2002;9(1):35e40. [9] Matsunou H, Konishi F. Papillary cystic neoplasm of the pancreas. A clinicopathologic study concerning the tumor aging and malignancy of nine cases. Cancer 1990;65:283e91. [10] Nakagohri T, Kinoshita T, Konishi M, Takahashi S, Gotohda N. Surgical outcome of solidpseudopapillary tumor of the pancreas. J Hepatobil Pancreat Surg 2008;15:318e21. [11] Nishihara K, Nagoshi M, Tsuneyoshi M, Yamaguchi K, Hayashi I. Papillary cystic tumors of the pancreas. Cancer 1993;71(1): 82e92. [12] Podevin J, Triau S, Miraille ´ E, Le Borgne J. Solid-pseudopapillary tumor of the pancreas: a clinical study of five cases, and review of the literature. Ann Chir 2003;128:543e8. [13] Sclafani LM, Reuter VE, Coit DG, Brennan MF. The malignant nature of papillary and cystic neoplasm of the pancreas. Cancer 1991;68:153e8. [14] Sto ¨mmer P, Kraus J, Stolte M, Giedl J. Solid and cystic pancreatic tumors: clinical, histochemical, and electron microscopic features in ten cases. Cancer 1991;67:1635e41. [15] Tipton SG, Smyrk TC, Sarr MG, Thompson GB. Malignant potential of solid pseudopapillary neoplasm of the pancreas. Br J Surg 2006;93:733e7. [16] Zinner MJ, Shurbaji MS, Cameron JL. Solid and papillary epithelial neoplasm of the pancreas. Surgery 1990;108(3):475e80. [17] Pyke CM, van Heerden JA, Colby TV, Sarr MG, Weaver AL. The spectrum of serous cystadenoma of the pancreas. Ann Surg 1992;215:132e9. [18] Siech M, Thumerer SU, Henne-Bruns D, Beger HG. Die Behandlung zystischer Tumoren des Pankreas. Radikal oder organsparend? Chirurg 2004;75:615e21. [19] Mao C, Guvendi M, Domenico DR, Kim K, Thomford NR, Howard JM. Papillary cystic and solid tumors of the pancreas: a pancreatic embryonic tumor? Studies of three cases and cumulative review of the world’s literature. Surgery 1995;118:821e8. [20] Madan AK, Weldon CB, Long WP, Johnson D, Raafat A. Solid and papillary epithelial neoplasm of the pancreas. J Surg Oncol 2004;85:193e8.

Frantz’s tumor [21] Papavramidis T, Papavramidis S. Solid pseudopapillary tumors of the pancreas: review of 718 patients reported in English literature. J Am Coll Surg 2005;6:965e72. [22] Horisawa M, Niinomi N, Sato T, Yokoi S, Oda K, Ichikawa M, et al. Frantz’s tumor (solid and cystic tumor of the pancreas) with liver metastasis: successful treatment and long-term follow up. J Pediatr Surg 1995;30:724e6. [23] Lam KY, Lo CY, Fan ST. Pancreatic solid-cystic-papillary tumor: clinicopathologic features in height patients from Hong Kong and review of the literature. World J Surg 1999;23: 1045e50. [24] Adamthwaite JA, Verbeke CS, Stringer MD, Guillou PJ, Menon KV. Solid pseudopapillary tumour of the pancreas: diverse presentation, outcome and histology. JOP 2006;7: 635e42. [25] Gedaly R, Toledano A, Millan G, Essenfeld H, Zambrano VJ. Treatment of liver metastases from a solid pseudopapillary tumor of the pancreas. J Hepatobiliary Pancreat Surg 2006;13: 587e90. [26] Tang LH, Aydin H, Brennan MF, Klimstra DS. Clinically aggressive solid pseudopapillary tumors of the pancreas. A report of two cases with components of undifferentiated carcinoma and a comparative clinicopathologic analysis of 34 conventional cases. Am J Surg Pathol 2005; 29:512e9.

125 [27] Fried P, Cooper J, Balthazar E, Fazzini E, Newall J. A role for radiotherapy in the treatment of solid and papillary neoplasm of the pancreas. Cancer 1985;56:2783e5. [28] Kaufman SL, Reddick RL, Stiegel M, Wild RE, Thomas Jr CG. Papillary cystic neoplasm of the pancreas: a curable pancreatic tumor. World J Surg 1986;10:851e9. [29] Levy P, Bougaran J, Gayet B. Diffuse peritoneal carcinosis of pseudo-papillary and solid tumor of the pancreas. Role of abdominal injury. Gastroenterol Clin Biol 1997;21(10):789e93. [30] Maffuz A, Bustamante Fde T, Silva JA, Torres-Vargas S. Preoperative gemcitabine for unresectable, solidpseudopapillary tumour of the pancreas. Lancet Oncol 2005;6:185e6. [31] Matsuda Y, Imai Y, Kawata S, Nishikawa M, Miyoshi S, Saito R, et al. Papillary-cystic neoplasm of the pancreas with multiple hepatic metastases: a case report. Gastroenterol Jpn 1987;22:379e84. [32] Shimizu M, Matsumoto T, Hirokawa M, Monobe Y, Iwamoto S, Tsunoda T, et al. Solid pseudopapillary carcinoma of the pancreas. Pathol Int 1999;49:231e4. [33] Strauss JF, Hirsch VJ, Rubey CN, Pollock M. Resection of a solid and papillary epithelial neoplasm of the pancreas following treatment with cisplatinum and 5-fluorouracil: a case report. Med Pediatr Oncol 1993;21:365e7. [34] Zauls JA, Dragun AE, Sharma AK. Intensity-modulated radiation therapy for unresectable solid pseudopapillary tumor of the pancreas. Am J Clin Oncol 2006;29:639e40.