Is Pancreatic Resection Justified for Metastasis of Papillary Thyroid Cancer?

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1 Is Pancreatic Resection Justified for Metastasis of Papillary Thyroid Cancer? A. MEYER and M. BEHREND Klinikum Deggendorf, Klinik für Viszeral-, Thorax-, Gefäß- und Kinderchirurgie, Deggendorf, Germany Abstract. Background: This case report describes a patient with symptomatic anaemia due to a bleeding duodenal metastasis from metastasising differentiated thyroid cancer (DTC), which was treated by partial duodenopancreatectomy (DP). Case Report: A 71-year old male was sent to hospital with severe anaemia. This patient had suffered multiple cervical recurrences of differentiated papillary thyroid cancer, which had been treated by several resections and irradiation, and an adrenal gland metastasis, via adrenalectomy. Abdominal computed tomography showed an enlarged pancreatic head, an upper gastrointestinal endoscopy revealed a bleeding ulcer in the duodenum, and a biopsy revealed metastasis from DTC. Due to the symptomatic metastasis, a partial DP was performed; the postoperative course was uneventful. Histopathological examination revealed metastasis of the DTC next to the papilla lying in the head of the pancreas, with growth into the muscularis propria of the duodenum. The patient survived for another 4ó years before dying from progressive metastatic disease elsewhere. Conclusion: DP for metastatic disease should be considered in selected patients for alleviation of the symptoms and prolongation of survival, as long as this operation is performed by experienced surgeons who can achieve minimal morbidity and mortality. In patients with metastasising differentiated thyroid cancer (DTC), radio-iodine ablation therapy is the therapy of first choice and can offer the patient several years of palliation. If the metastases are radio-iodine-resistant, the treatment is challenging. In the case of an acute symptomatic metastasis, a surgical approach with metastasectomy may be indicated, in spite of a metastasised disease. This case report describes Correspondence to: Privatdozent Dr. med. Matthias Behrend, Klinikum Deggendorf, Klinik für Viszeral-, Thorax-, Gefäß- und Kinderchirurgie, Perlasberger Straße 41, Deggendorf, Germany. Tel: , Fax: , Matthias.Behrend@Klinikum-Deggendorf.de Key Words: Metastasising thyroid cancer, bleeding duodenal metastasis, duodenopancreatectomy. a patient with symptomatic anaemia due to a bleeding duodenal metastasis from DTC, which was treated by partial duodenopancreatectomy (DP). Case Report A total thyreoidectomy with cervical bilateral lymphadenectomy was carried out on a 62-year-old man for DTC, which had been previously confirmed histologically by fine-needle biopsy. Histopathological examination revealed differentiated papillary thyroid cancer with invasion of the perithyroidal tissue, but without spread to the locoregional lymph nodes; the tumour category was T4 N0 M0. Postoperatively, radio-iodine ablation therapy was carried out using 131-iodine at a dose of 3.7 GBq. After the ablation therapy, suppression therapy with T4 was started. The first post-dose whole-body scan showed slight tracer accumulation corresponding to remaining thyroid tissue, while the second post-dose whole-body scan showed no tracer accumulation. One year after the operation, the thyroglobulin (Tg) level, that had proved to be normal after the ablation therapy, increased to 13.6 ng/ml (normal <2) and decreased to a level of 10 ng/ml during further follow-up, without any clinical or imaging suspicion of recurrence or metastatic spread. Two years after the operation, the Tg level had increased to ng/ml. Cervical imaging revealed a right-sided cervical tumour, while fine-needle biopsy showed papillary thyroid cancer. A whole-body scintigraphy using 131-iodine showed no pathological tracer accumulation, thus demonstrating that the new local recurrence was non-avid to radio-iodine ablation therapy. Right-sided cervical exploration was carried out revealing eight lymph node metastases of papillary thyroid cancer. One month after this second operation, the Tg level had decreased to 14.1 ng/ml, but repeated cervical imaging again revealed local recurrence in the right-sided space of the former thyroid gland, which was histologically confirmed by fine-needle biopsy. Complete staging of the patient showed no further metastatic lesions. Surgical resection and lymphadenectomy revealed a local recurrence and two lymph node metastases of papillary thyroid cancer. Postoperatively, /2006 $

2 the Tg level was still elevated at 29.9 ng/ml, although imaging controls, including cervical ultrasound and tumour scintigraphy with technetium, showed no suspicion of tumour recurrence. Six months after the third operation, the Tg level was 22.6 ng/ml and cervical imaging detected right-sided cervical and mediastinal recurrence. A renewed cervical exploration with resection of the right-sided tumour was carried out, showing papillary thyroid cancer as a metastasis in the cervical tissue localised between the superior caval vein, oesophagus and trachea. Postoperatively, the Tg level decreased to 15.6 ng/ml, and a fistula had developed at the right sternoclavicular junction, which was treated with excision five months later. During further follow-up, the Tg level had again increased to ng/ml, and imaging procedures revealed a newly-developed cervical and mediastinal tumour. Because a new surgical excision was not favoured by the surgeons due to four previous operations and the postoperative complication after the last operation, percutaneous cervical irradiation up to a dose of 59.4 Gy with a single dose of 1.8 Gy given in 33 fractions was performed. After the irradiation, the Tg level decreased continuously to a level of 17.2 ng/ml. One year after the irradiation, new cervical recurrence could be detected by imaging methods and the Tg level was 66.9 ng/ml. Due to the radio-iodine non-responsive thyroid cancer, therapy with retinoids was started for redifferentiation of the tumour to increase the radio-iodine uptake, but this therapy was stopped six months later due to severe side-effects. At the end of this treatment, restaging using cervical and thoracic computed tomography (CT) showed stable cervical disease, but the occurrence of a tumour localised at the right adrenal gland. One month after completion of the redifferentiation therapy, the patient was admitted to hospital for severe anaemia with a haemoglobin level of 6.2 g/dl. Apart from pulmonary metastasis, thoracic and abdominal CT revealed a tumour of the right adrenal gland with a diameter of 6.5 cm. A biopsy of this tumour revealed adrenal metastasis of the DTC, therefore a right-sided adrenalectomy and resection of the tumour was carried out. Histopathological examination showed metastases of papillary thyroid cancer and the Tg level decreased to 28.1 ng/ml postoperatively. However, the anaemia persisted and worsened. Two months later, when the patient needed daily units of blood due to unidentified bleeding, he was referred to our unit. A blood pool scintigraphy revealed bleeding in the right lower abdomen; abdominal CT showed an enlarged pancreatic head (Figure 1) that had not been detected in the previous CT scan performed for the adrenal metastasis. Upper gastrointestinal endoscopy revealed a bleeding ulcer in the duodenum, and a biopsy showed metastasis from DTC. Because of the daily need for 2-4 units of blood, a resection of the metastasis was carried out using a partial PD Whipple-Kausch, with Figure 1. Large tumour mass from DTC metastasis in the head of the pancreas leading to upper gastrointestinal bleeding with severe anaemia. uneventful postoperative course. Histopathological examination revealed metastasis of the papillary thyroid cancer (Figure 2a) next to the papilla Vater lying in the head of the pancreas and confined by a capsule of pancreatic tissue with growth into the muscularis propria of the duodenum. Immunohistochemistry was positive for Tg (Figure 2b). Postoperatively, the Tg level decreased to 4.6 ng/ml. One year later, the Tg level had increased to 14.2 ng/ml. New imaging revealed cervical tumour recurrence and multiple metastases localised in the lung and liver. Further therapy was refused by the patient. Two years later, a new metastasis in the former space of the right adrenal gland occurred with infiltration of the right kidney and compression of the inferior caval vein. Seven months later and 4ó years after the DP, the patient died due to progressive abdominal metastatic spread. Discussion Duodenal metastases are very uncommon, accounting for 1% to 3% of all duodenal malignancies (1, 2), but they should be taken into consideration in patients presenting with upper gastrointestinal bleeding and a previous history of malignancy (3-5). The most common malignancies to metastasise to the periampullary region occur either in the colon, lung, breast or kidney, but there are scattered reports of metastases at other cancer sites (3, 6). In patients with DTC, distant metastases occur in 10%-20% of all cases and are usually localised in the lung and bone (7). Less common sites of metastases are the brain, liver and skin. Occurrence of metastases at other sites, e.g., the duodenum, is exceptional. In our patient, the metastasis of the DTC next to the papilla Vater with growth into the muscularis propria of the duodenum could be clearly 2270

3 Meyer and Behrend: Duodenopancreatectomy for Duodenal Metastasis identified by histopathological examination. However, in a case report, ectopic microscopic thyroid follicles, localised in the duodenum, have been reported with positive immunoreaction for Tg (8). For patients with metastatic DTC, radioactive iodine therapy is the gold standard for treatment and remains a primary treatment modality, frequently offering the patient several years of palliation. In the event of resistance to radio-iodine ablation, the treatment is challenging. In the case of an isolated metastasis, surgery is one treatment option in patients in good medical condition with low surgical risk offering the chance of cure. Stojadinovic et al. and Pak et al. demonstrated that a surgical approach with metastasectomy in patients with well-differentiated thyroid cancer was associated with improved survival on performing a complete metastasectomy, and improvement of quality of life in cases of symptomatic distant metastasis when palliative resection was performed (9, 10). However, a surgical approach can also be indicated in the case of a symptomatic metastasis for rapid amelioration of disorders, even in patients with multiple metastases, as in the case of our patient to stop the bleeding. Although surgical resections of metastatic lesions of the liver, lung and brain have proved to be useful, the role of surgical resection in the case of a solitary metastatic or locally recurrent malignancy in the duodenal or periampullary region has not yet been defined. Previous reports have advocated a conservative approach for periampullary metastatic lesions, because of the historically high rates of perioperative morbidity and mortality of DP in patients with primary pancreatic adenocarcinoma on the one hand, and the expected short survival time in patients with multiple metastases on the other. For many years, this procedure was characterised as a difficult, hazardous and somewhat questionable procedure, associated with high morbidity rates exceeding 60% and mortality rates approaching 25%. This has led to a reluctance to treat these metastases with DP (11). However, during the past two decades, the results from this procedure have gradually improved, and the Whipple operation and its modifications have evolved as safe and effective procedures for several indications. In addition to advances in surgical techniques and a better understanding of pancreatic diseases, numerous improvements in diagnostic and interventional radiology, surgical techniques, intensive and perioperative care and management of complications have contributed to the currently low mortality of DP (12). In recent years, the operative mortality for DP has dramatically decreased, with mortality rates of less than 5%. Today the reported major causes for postoperative mortality are intra-abdominal bleeding, sepsis related to pancreaticojejunal anastomotic leakage and cardiopulmonary failure. Although the quoted morbidity rate has also decreased, it is still around 40% (12-14). One of the most important factors affecting mortality and morbidity is the emergence of specialised centres focussing on pancreatic surgery. Several recently published series have revealed a distinct association between high patient volumes and decreased mortality rates (15-17). Today PD is also an accepted treatment for patients with benign diseases such as chronic pancreatitis, islet cell tumours and cystic neoplasms (14). With this significant decrease in surgical complications, the indications for this procedure may now be expanded to resection for metastatic disease to the periampullary region or to the pancreas. To date, only a few case reports and small series exist concerning the role of DP in metastatic disease but, in most of these reports, an aggressive surgical approach with DP was suggested for the management of these lesions (3, 5, 6, 18-20). Here, we present the first case report of a resection of the head of the pancreas due to bleeding metastasis of a papillary thyroid cancer. A median survival of months can be achieved with good palliation, with a 5-year survival of 17% (3, 6, 20). Indeed, our patient survived for more than 4 years after the DP. In contrast, the median survival for pancreatic cancer for all patient groups reported in the literature ranges between only 12 months and 18 months, with a 5-year survival rate of approximately 5%-15% (12, 21-23). Therefore, a survival rate can be achieved that is at least as good as that for patients with a primary periampullary carcinoma. Additionally, the DP used in our patient was the only method for treating the severe anaemia with a satisfactory and long-lasting effect. Therefore, we believe that surgery, although an aggressive therapy, should remain a viable treatment option for carefully selected patients, even with palliative intent. To summarise, from this case report and from the few cases documented in the literature, it can be concluded that DP for metastatic disease can be considered in selected patients for alleviation of the symptoms and prolongation of survival, as long as this operation is performed by experienced surgeons who can achieve minimal morbidity and mortality. References 1 Farmer RG and Hawk WA: Metastatic tumours of the small bowel. Gastroenterology 47: , Kadakia SC, Parker A and Canales L: Metastatic tumors to the upper gastrointestinal tract: endoscopic experience. Am J Gastroenterol 87: , Le Borgne J, Partensky C, Glemain P, Dupas B and de Kerviller B: Pancreaticoduodenectomy for metastatic ampullary and pancreatic tumors. Hepatogastroenterology 47: , Cremon C, Barbara G, De Giorgio R et al: Upper gastrointestinal bleeding due to duodenal metastasis from primary lung carcinoma. Dig Liver Dis 34: ,

4 Figure 2. a) Tissue section from the tumour. Hematoxylin/Eosin stain. Magnification 10 x 40. Cohesive growing tumor cells in trabecular units. b) Immunohistology for thyreoglobin from the tumour resection of the pancreatic head and duodenum. Magnification 10 x 20. Strong positivity for thyreoglobin. 2272

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