Keywords

Kidney Transplantation; Liver Diseases; Pancreaticoduodenectomy Polycystic Kidney Diseases

INTRODUCTION

Pancreatic resection remains associated with a high morbidity, particularly in patients with underlying comorbidities or those who have had previous abdominal surgery [1, 2]. Polycystic disease is a rare disorder, which most commonly manifests in the kidney [3, 4]. The liver is the second most commonly involved organ [5]. Polycystic kidney disease is a common indication for kidney transplantation and frequently requires bilateral nephrectomy due to pain, hemorrhage into cysts or infection of the cysts [6, 7]. Hepatic cysts can be treated by percutaneous drainage, laparoscopic deroofing, or liver resection and occasionally, polycystic liver disease can lead to complications that require liver transplantation [8, 9]. Some authors have suggested combined liver/kidney transplantation if both organs are involved [10].

Recently, an increased mortality rate due to other malignancies has been reported in patients who previously underwent renal transplantation for polycystic kidney disease [11]. Among these patients, one patient died from pancreatic cancer [11]. In particular, for polycystic kidney disease Potter III patients an increased rate of developing pancreatic cancer is well established [12, 13]. Polycystic livers can grow to an enormous size and occupy a large amount of the available intraabdominal space [14]. This results in significant discomfort for the patient and dislodgement of other intra-abdominal organs with distortion of the vascular anatomy. Frequently, the entire small and large bowels are forced into the left lower quadrant. Understandably, liver transplantation in these cases is technically challenging especially when dealing with a liver weighing as much as 20 kilograms [8]. Similarly, any upper gastrointestinal tract procedure must be considered difficult due to the lack of space and the abnormal anatomy [15]. We report a patient with polycystic liver and kidney disease who successfully underwent a Whipple’s procedure for pancreatic adenocarcinoma.

CASE REPORT

The patient was a 71-year-old slightly obese African American female with polycystic liver and kidney disease. She underwent bilateral native nephrectomy with splenectomy in 1997 and subsequently a cadaveric kidney transplantation in 1999. Graft function was excellent and the current immunosuppression consisted of triple drug therapy including cyclosporine A with trough levels between 50 and 100 ng/mL, mycophenol-mofetil (2 g daily), and prednisone (5 mg daily). Because of persistent abdominal pain over the last four years, she had multiple percutaneous cystotomies and ablations of liver cysts. In November 2005, the patient presented with symptoms of cholangitis and sepsis. Ultrasound of the right upper quadrant revealed a dilated common bile duct and a markedly enlarged liver with multiple cysts replacing virtually all of the normal hepatic parenchyma. An endoscopic retrograde cholangiopancreatogram (ERCP) was then performed which confirmed the long distal common bile duct stricture (Figure 1).

Figure 1. ERCP: stenosis of the common bile duct.

Brushings were obtained and a 10 French biliary endoprosthesis was placed. Pathologic examination of the brushings revealed adenocarcinoma.

Further investigations included a computed tomography (CT) scan (Figure 2) showing a hypodense mass measuring 1.8x2.2 cm in the head of the pancreas and a massive liver with multiple intrahepatic cysts. A FDG-PET scan revealed a focus of intense hypermetabolic activity correlating with the pancreatic head mass seen on CT. An endoscopic ultrasound demonstrated a 1.8x1.6 cm hypoechogenic mass in the head of the pancreas. There was some focal dilation of the proximal pancreatic duct. No peripancreatic lymphadenopathy was identified.

Figure 2. CT scan. a. Pancreatic mass. b. Polycystic liver with dislocation of intra-abdominal organs.

In December 2005, the patient underwent pancreaticoduodenectomy. A bilateral subcostal incision was used to access the abdominal cavity. Because of the polycystic liver disease and the extremely enlarged liver, the right hepatic lobe extended caudally across the midline pushing all intra-abdominal organs inferiorly and to the left. A classical pancreaticoduodenectomy including a thorough retroperitoneal lymph node dissection was carried out despite the enormous size of the liver. After mobilization of the right hemicolon and completion of Kocherization of the duodenum, the gallbladder was taken down and the common bile duct was divided immediately below the insertion of the cystic duct. The proximal bile duct was submitted for frozen section that was negative. During the reconstruction phase, pancreatic and biliary stents were placed across the respective anastomoses and externalized through the right abdominal wall. A Jackson-Pratt drain was placed beneath the pancreaticojejunostomy and brought out through the left abdominal wall. The intraoperative course was unremarkable and the patient was returned to the surgical intensive care unit and was extubated on the following day without incident. The final pathology revealed a 2.3 cm pancreatic adenocarcinoma with three of 21 lymph nodes positive for metastatic disease. The final staging was pT3N1M0, G2.

Stress steroid doses were given perioperatively and tapered to the baseline level. Her postoperative course was complicated by poor nutritional intake and oral herpes simplex virus infection. The herpes simplex virus infection was successfully treated with acyclovir 400 mg twice daily. The function of the kidney allograft remained stable throughout her hospitalization with measured creatinine levels less than 1.0 mg/dL. She was discharged four weeks later. She was doing well at three months follow up and conversion of immunosuppression to a mammalian target of rapamycin (mTOR) inhibitor was discussed. Unfortunately, the patient expired due to cardiac failure unrelated to the surgical procedures few weeks later.

DISCUSSION

This case shows the feasibility of pancreatic resection in a patient with a massively enlarged polycystic liver who suffers multiple comorbidities and has undergone kidney transplantation. Her postoperative course was prolonged but she ultimately recovered well, however she died unrelated to the surgical procedure from her underlying comorbidities.

Several aspects make this case unique. First, little is known on the development of pancreatic cancer following solid organ transplantation [15]. However, there is evidence that patients with polycystic diseases have an increased risk of developing a pancreatic malignancy [16, 17]. Second, it is not known whether the conventional immunosuppression with calcineurin inhibitor would promote pancreatic malignancy. Recent reports show that mTOR inhibitors do have an antitumor effect [18]. It has thus been suggested that patients who develop de novo post-transplant malignancies should be switched to sirolimus or everolimus [19]. Sirolimus may have a beneficial impact on the course of pancreatic cancer [20]. Sirolimus as part of the chemotherapeutic regimen may be superior to the standard regimen included gemcitabine [21]. However, judious care must be taken when using mTOR inhibitors during the immediate postoperative period due to the antiproliferative effects that may result in severe wound healing disturbances [22]. A failure of pancreatic anastomosis can lead to disastrous complications [23].

The third interesting aspect in this case is the surgical procedure. Due to previous bilateral nephrectomies and a splenectomy, there were multiple adhesions. Moreover, the anatomy of the abdominal organs was significantly distorted due to the enormous liver [24]. Nevertheless, the intraoperative blood loss was low. Comprehensive management of this patient requires multi-specialty collaboration including transplant nephrology, hepatology, interventional radiology, oncology, hepatobiliary and transplant surgery. For this particular case the involvement of a transplant team certainly may have been beneficial. Maeda et al. reported on an emergency pancreaticoduodenectomy for pancreatic metastasis from renal cell carcinoma in a patient with von Hippel-Lindau disease [25]. Also this patient had undergone nephrectomy. Von Hippel-Lindau disease and polycystic liver/kidney disease both seem to be associated with pancreatic malignancies [26]. Surgical resection remains the cornerstone in the treatment of the pancreatic cancer [1]. This case report illustrates that pancreaticoduodenectomy can be safely performed in patients with polycystic liver and kidney disease. Moreover, this case also highlights the need for comprehensive evaluation of biliary strictures in polycystic disease patients [27, 28]. Advanced understanding of immunosuppression will help to optimize the chemotherapeutic and immunosuppressive agents in the polycystic liver and kidney disease patients with pancreatic cancer.

Conflict of interest

Dr. Bonatti was sponsored by the Detiger fellowship. The other authors have no potential conflicts of interest

References

1. Tran KT, Smeenk HG, van Eijck CH, Kazemier G, Hop WC, Greve JW, et al. Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure: a prospective, randomized, multicenter analysis of 170 patients with pancreatic and periampullary tumors. Ann Surg 2004; 240:738-45. [PMID 15492552]
2. Alexakis N, Sutton R, Raraty M, Connor S, Ghaneh P, Hughes ML, et al. Major resection for chronic pancreatitis in patients with vascular involvement is associated with increased postoperative mortality. Br J Surg 2004; 91:1020-6. [PMID 15286965]
3. Zerres K, Völpel MC, Weiss H. Cystic kidneys. Genetics, pathologic anatomy, clinical picture, and prenatal diagnosis. Hum Genet 1984; 68:104-35. [PMID 6500563]
4. Mcgeoch JE, Darmady EM. Polycystic disease of kidney, liver and pancreas; a possible pathogenesis. J Pathol 1976; 119:221-8. [PMID 134139]
5. Arnold HL, Harrison SA. New advances in evaluation and management of patients with polycystic liver disease. Am J Gastroenterol 2005; 100:2569-82. [PMID 16279915]
6. Gagnadoux MF, Habib R, Levy M, Brunelle F, Broyer M. Cystic renal diseases in children. AdvNephrol Necker Hosp 1989; 18:33-57. [PMID 2493722]
7. Fuller TF, Brennan TV, Feng S, Kang SM, Stock PG, Freise CE. End stage polycystic kidney disease: indications and timing of native nephrectomy relative to kidney transplantation. J Urol 2005; 174:2284-8. [PMID 16280813]
8. Pirenne J, Aerts R, Yoong K, Gunson B, Koshiba T, Fourneau I, et al. Liver transplantation for polycystic liver disease. Liver Transpl 2001; 7:238-45. [PMID 11244166]
9. Kornprat P, Cerwenka H, Bacher H, El-Shabrawi A, Tillich M, Langner C, Mischinger HJ. Surgical therapy options in polycystic liver disease. Wien KlinWochenschr 2005; 117:215-8. [PMID 15875761]
10. Jeyarajah DR, Gonwa TA, Testa G, Abbasoglu O, Goldstein R, Husberg BS, et al. Liver and kidney transplantation for polycystic disease. Transplantation 1998; 66:529-32. [PMID 9734499]
11. Errasti P, Manrique J, Lavilla J, Rossich E, Hernandez A, Pujante D, et al. Autosomal-dominant polycystic kidney disease: high prevalence of graft loss for death-related malignancies and cardiovascular risk factors. Transplant Proc 2003; 35:1717-9. [PMID 12962769]
12. Niv Y, Turani C, Kahan E, Fraser GM. Association between pancreatic cystadenocarcinoma, malignant liver cysts, and polycystic disease of the kidney. Gastroenterology 1997; 112:2104-7. [PMID 9178704]
13. Takeh H, Phillipart P, Brandelet B, Nemec E, Bidgoli SJ, da Costa PM. Pancreatic mucinous cystadenoma associated with celiac disease and polycystic kidneys. Case report and short review of the [PMID 12143249]
14. Morales JM, Prieto C, Oliet A, Praga M. Hepatorenal polycystic disease in the adult (Potter type III). Med Clin (Barc) 1987; 89:174-5. [PMID 3626673]
15. Petrowsky H, Schuster H, Irani S, Schäfer M, Jochum W, Schmid C, et al. Pancreatic cancer in cystic fibrosis after bilateral lung transplantation. Pancreas 2006; 33:430-2. [PMID 17079951]
16. Sakurai Y, Shoji M, Matsubara T, Ochiai M, Funabiki T, Urano M, et al. Pancreatic ductal adenocarcinoma associated with Potter type III cystic disease. J Gastroenterol 2001; 36:422-8. [PMID 11428590]
17. Otani T, Makuuchi M. Potter type III cystic disease and pancreatic malignancies. J Gastroenterol 2001; 36:438-40. [PMID 11428594]
18. Smolewski P. Recent developments in targeting the mammalian target of rapamycin (mTOR) kinase pathway. Anticancer Drugs 2006; 17:487-94. [PMID 16702804]
19. Campistol JM, Eris J, Oberbauer R, Friend P, Hutchison B, Morales JM, et al. Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am SocNephrol 2006; 17:581-9. [PMID 16434506]
20. Bruns CJ, Koehl GE, Guba M, Yezhelyev M, Steinbauer M, Seeliger H, et al. Rapamycin-induced endothelial cell death and tumor vessel thrombosis potentiate cytotoxic therapy against pancreatic cancer. Clin Cancer Res 2004; 10:2109-19. [PMID 15041732]
21. Stephan S, Datta K, Wang E, Li J, Brekken RA, Parangi S, et al. Effect of rapamycin alone and in combination with antiangiogenesis therapy in an orthotopic model of human pancreatic cancer. Clin Cancer Res 2004; 10:6993-7000. [PMID 15501979]
22. Dean PG, Lund WJ, Larson TS, Prieto M, Nyberg SL, Ishitani MB, et al. Wound-healing complications after kidney transplantation: a prospective, randomized comparison of sirolimus and tacrolimus. Transplantation 2004; 77:1555-61. [PMID 15239621]
23. Howard JM. Pancreatojejunostomy: leakage is a preventable complication of the Whipple resection. J Am CollSurg 1997; 184:454-7. [PMID 9145064]
24. Bistritz L, Tamboli C, Bigam D, Bain VG. Polycystic liver disease: experience at a teaching hospital. Am J Gastroenterol 2005; 100:2212-7. [PMID 16181371]
25. Maeda H, Okabayashi T, Kobayashi M, Araki K, Kohsaki T, Nishimori I, et al. Emergency pancreatoduodenectomy for pancreatic metastasis from renal cell carcinoma in a patient with von Hippel- Lindau disease: a case report. Dig Dis Sci 2006; 51:1383-7. [PMID 16868829]
26. Naitoh H, Shoji H, Ishikawa I, Watanabe R, Furuta Y, Tomozawa S, et al. Intraductal papillary mucinous tumor of the pancreas associated with autosomal dominant polycystic kidney disease. J GastrointestSurg 2005; 9:843-5. [PMID 15985242]
27. Malka D, Hammel P, Vilgrain V, Fléjou JF, Belghiti J, Bernades P. Chronic obstructive pancreatitis due to a pancreatic cyst in a patient with autosomal dominant polycystic kidney disease. Gut 1998; 42:131- 4. [PMID 9505899]
28. Hasegawa T, Kim M, Kitayama Y, Kitamura K, Hiranaka T. Choledochal cyst associated with polycystic kidney disease: report of a case. HPB Surg 1999; 11:185-9. [PMID 10371064]