ročník 11,2003 č.4
Klinika

Uncommon tumors of the pancreas

Jeppsson, B.

Department of Surgery
Malmö University Hospital

"If they can operate, it is good for you". This statement has been ascribed to late professor Francis D.Moore, Boston, USA many years ago. It reflects a fact that is still true today, that surgical removal of a tumor is still the only hope for cure for many malignant lesions. This is not only true for surgical treatment of primary malignant lesions, but also for metastatic lesions. Most experience exists for liver secondaries from e.g. colorectal cancers. In this selected group of patients long-time survivors of 25 - 30 % have been reported in many series. It seems that there is a stage of isolated liver metastases. This will give us an oppurtunity for surgical therapy, but otherwise all patients would die if untreated.
A similar situation may prevail in the pancreas. In autopsy series, metastases to the pancreas from tumors outside the organ have been reported in as many as 11 % of patients with malignant tumors in the pancreas (1).
Metastatic lesions in the pancreas can arise in many organs (table 1) and in most patients it is part of a wide-spread disease.

Kidney Oesophagus
Lung Uterus
Breast Salivary gland
Colon Prostate
Melanoma Liver
Stomach Testis
Extrahepatic Bile duct Thyroid
Ovary Bone
Duodenum Brain
Tab. No.1 - Sites of primary tumor presenting with pancreatic metastasis

The most common are from kidney, lung, breast, colon and melanoma. This is also the tumors, where we have the largest experience.
The mode of spread of metastases from these different primary tumors is difficult to understand, but may include affinity of tumor cells to certain cell-receptors etc. Metastases from renal cell carcinoma to the pancreas seem to be the most frequently occurring. In these cases the spead may be hematogenous, along the draining collateral veins from a hypervascular primary tumor, or lymphatic by retrograde lymph flow from retroperitoneal nodes (2).
Most patients with secondary pancreatic tumors present in a similar way to those with primary tumors. The symptoms described are abdominal pain, weight loss, gastrointestinal bleedning, anemia and jaundice (3). There may be an abdominal mass and pancreatic dysfunction, but some patients are symptomless (4).
The diagnostic work-up include spiral CT and angiography. The appearance of the tumor with these modalities may reveal the nature of the pancreatic lesion. In contrast to most primary pancreatic tumors, that are hypodense and hypovascular, metastases from renal cell carcinomas appear hypervascular. Hypervascular lesions may also stem from neuroendocrine or lymphamatous tumors. When there is suspicion of a neuroendocrine tumor, a scintigraphic assessment of peptides is of value. Metastases from melanomas pose special problems. In these cases metastases outside pancreas are frequent and here PET scanning appears to be valuable (5,6). The problem with the PET scanning is that it is difficult to have a detailed anatomical localisation and it is therefore considiered to be complementary to other imaging techniques.
Surgical resection is the only curative treatment and many tumors of the pancreas are resected without preoperative or intraoperative histological verification. Fine-needle aspiration is often inaccurate and carries a significant risk of tumor seeding. Resection is justified in light of the experience in most centers of low morbidity and mortality in pancreatic resection today. The surgical therapy must be chosen according to tumor localization and may therefore be more varied than in cancers of exocrine pancreas. In most reports some kind of resection has been chosen, either pylorus-preserving pancreatoduodenectomy or resection of the head with preservation of duodenum. Rarely is total pancreatectomy necessary.
The discovery of metastatic lesions generally implies a poor prognosis in cancer. There are some important exceptions, such as liver metastases from colorectal cancer, mentioned above. The same is also true for metastases to pancreas, where long-time prognosis is astonishingly good, especially in cases of metastases from renal cell carcinoma. One must bear in mind that in both instances we deal with a very selected group of patients.
Thompson and Heffess reported a series of 21 patients who underwent pancreatic resection for renal cell carcinoma metastases with an 81 % 5 year survival rate (7). Sohn et al described 10 patients who underwent pancreatic resection with an actuarial survival rate of 75 % (8).
In recent publications Zacharoulis and coworkers report 3 patients, where two were resected and are alive 2 years and 9 yeras respectively and one patient with an irresectable lesions still alive after 4 years (9). In a series of 14 patients with metastases to pancreas 83 months (median) after nephrectomy, 50% of the patients were alive at 32 months (10).

Author No patients Time from nephrectory to Metastases Follow - up (mo) Survival
Thompson et al 21 13 years   74 mo/overall
Sohn et al 10     7 patients at 5 year
Takashi et al 3     2,9 and 4 years
Lan et al 14 83 mo 32 mo 7 patients
Kassahian et al 5 4,6,13,14 and 15 years 24 mo 4 alive, 1 dead at 60 mo
Tab. No.2 - Results of resection of renal cell carcinoma metastases to pancreas

When it comes to metastases from melanoma the survival outcome is in general dismal with a median survival of 6 - 12 months. The survival outcomes of patients with complete surgical resection are generally better. Wood et al reported six patients with isolated metastases to the pancreas, treated surgically. The median survival in this group was 24 months and the 5-year survival was 50 % (11). Several other series support the result of improved survival in patients with complete resection of isolated pancreatic metastases (12). Nikfarjam et al report this year two cases of surgical removal of melanoma metastases to pancreas, both arising from ocular melanoma 3 and 13 years earlier (13).
The surgical therapy is still very justified when it comes to metastatic lesions in the pancreas and the results following resection of renal cell carcinoma are encouraging, although the patients that can be offered this therapy is very small.

References

  1. Cubilla AL, Fitzgerald PJ. Tumours of the exocrine pancreas. Atlas of tumour pathology series 2. Fascicle 19, Washington DC: Armed Forces Institute of Pathology 1984.
  2. Kassabian A, Stein J, Jabbour N et al: Renal cell carcinoma metastatic to the pancreas: single -institution series and review of the literature. Urology 56:211-15, 2000.
  3. Robins EG, Franceschi D, Barkin JS: Solitary metastatic tumors to the pancreas: a case report abd review of the literature. Am J Gastroenterol 91: 2414-7, 1996.
  4. Hirota T, Tomida T, Iwasa M et al: Solitary pancreatic metastasis occurring eight years after nephrectomy for renal cell carcinoma. A case report and surgical review. Int J Pancreatol 19: 145-53, 1996.
  5. Prichard RS, Hill AD, Skehan SJ, O´Higgins NJ: Positron emmission tomography for staging and management of malignant melanoma. Br J Surg 89:389-96, 2002.
  6. Rinne D, Baum RP, Hor G, Kaufmann R: Primary staging and follow-up of high risk melanoma patients with whole-body 18F-fluorodeoxyglucose positron emission tomography:results of a prospective study of 100 patients. Cancer 82: 1664-71, 1998.
  7. Thompson L, HeffessC: Renal cell carcinoma to the pancreas in surgical pathology material. Cancer 89:1076-88, 2000.
  8. Sohn TA, Yeo CJ, Cameron JL et al: Renal cell carcinoma metastatic to the pancreas: results of surgical management. J Gastrointest Surg 5: 346-51, 2001.
  9. Zacharoulis D, Asopa V, Karvounis E, Williamson RCN: Resection of renal metasases to the pancreas: a surgical challenge. HPB Surgery 5:137-41, 2003.
  10. Lau CH, Wei AC, Hanna SS et al: Pancreatic resection for metastatic renal cell carcinoma: presentatioin, treatment and outcome. Ann Surg Oncol 10:992-6, 2003.
  11. Wood TF, DiFronzo LA, Rose DM et al: Does complete resection of melanoma metastatic to solid intra-abdominal organs improve survival? Ann Surg Oncol 8: 658-62, 2001.
  12. Wong JH, Skinner KA, Kim KA et al: The role of surgery in the treatment of nonregionally recurrent melanoma. Surgery 113:389-94, 1993.
  13. Nikfarjam M, Evans P, Christophi C: Pancreatic resection for metastatic melanoma. HPB Surgery 5: 174-79, 2003.

Address for correspondence:

Bengt Jeppsson MD, PhD, FRCS (Engl.)
Professor of surgery
Malmo University Hospital
Department of surgery
Malmö 205 02 Sweden