ANTICANCER RESEARCH 26: 2269-2274 (2006)

Is Pancreatic Resection Justified for of Papillary ?

A. MEYER and M. BEHREND

Klinikum Deggendorf, Klinik für Viszeral-, Thorax-, Gefäß- und Kinderchirurgie, 94469 Deggendorf, Germany

Abstract. Background: This case report describes a patient a patient with symptomatic anaemia due to a bleeding with symptomatic anaemia due to a bleeding duodenal duodenal metastasis from DTC, which was treated by partial metastasis from metastasising differentiated duodenopancreatectomy (DP). (DTC), which was treated by partial duodenopancreatectomy (DP). Case Report: A 71-year old male was sent to hospital with Case Report severe anaemia. This patient had suffered multiple cervical recurrences of differentiated , which had A total thyreoidectomy with cervical bilateral been treated by several resections and irradiation, and an lymphadenectomy was carried out on a 62-year-old man for adrenal gland metastasis, via adrenalectomy. Abdominal DTC, which had been previously confirmed histologically by computed tomography showed an enlarged pancreatic head, an fine-needle biopsy. Histopathological examination revealed upper gastrointestinal endoscopy revealed a bleeding ulcer in the differentiated papillary thyroid cancer with invasion of the duodenum, and a biopsy revealed metastasis from DTC. Due to perithyroidal tissue, but without spread to the locoregional the symptomatic metastasis, a partial DP was performed; the lymph nodes; the tumour category was T4 N0 M0. postoperative course was uneventful. Histopathological Postoperatively, radio- ablation therapy was carried examination revealed metastasis of the DTC next to the papilla out using 131-iodine at a dose of 3.7 GBq. After the ablation lying in the head of the , with growth into the therapy, suppression therapy with T4 was started. The first muscularis propria of the duodenum. The patient survived for post-dose whole-body scan showed slight tracer another 4ó years before dying from progressive metastatic accumulation corresponding to remaining thyroid tissue, elsewhere. Conclusion: DP for metastatic disease should while the second post-dose whole-body scan showed no be considered in selected patients for alleviation of the symptoms tracer accumulation. One year after the operation, the and prolongation of survival, as long as this operation is (Tg) level, that had proved to be normal after performed by experienced surgeons who can achieve minimal the ablation therapy, increased to 13.6 ng/ml (normal <2) morbidity and mortality. and decreased to a level of 10 ng/ml during further follow-up, without any clinical or imaging suspicion of recurrence or In patients with metastasising differentiated thyroid cancer metastatic spread. Two years after the operation, the Tg (DTC), radio-iodine ablation therapy is the therapy of first level had increased to 101.6 ng/ml. Cervical imaging revealed choice and can offer the patient several years of palliation. a right-sided cervical tumour, while fine-needle biopsy If the metastases are radio-iodine-resistant, the treatment is showed papillary thyroid cancer. A whole-body challenging. In the case of an acute symptomatic metastasis, using 131-iodine showed no pathological tracer a surgical approach with metastasectomy may be indicated, accumulation, thus demonstrating that the new local in spite of a metastasised disease. This case report describes recurrence was non-avid to radio-iodine ablation therapy. Right-sided cervical exploration was carried out revealing eight metastases of papillary thyroid cancer. One month after this second operation, the Tg level had Correspondence to: Privatdozent Dr. med. Matthias Behrend, decreased to 14.1 ng/ml, but repeated cervical imaging again Klinikum Deggendorf, Klinik für Viszeral-, Thorax-, Gefäß- und revealed local recurrence in the right-sided space of the Kinderchirurgie, Perlasberger Straße 41, 94469 Deggendorf, former thyroid gland, which was histologically confirmed by Germany. Tel: 49-991-380-3000, Fax: 49-991-380-3010, e-mail: [email protected] fine-needle biopsy. Complete staging of the patient showed no further metastatic lesions. Surgical resection and Key Words: Metastasising thyroid cancer, bleeding duodenal lymphadenectomy revealed a local recurrence and two lymph metastasis, duodenopancreatectomy. node metastases of papillary thyroid cancer. Postoperatively,

0250-7005/2006 $2.00+.40 2269 ANTICANCER RESEARCH 26: 2269-2274 (2006) 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 . 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 115.2 ng/ml, and imaging procedures revealed a newly-developed cervical and mediastinal tumour. Because a new surgical excision was not Figure 1. Large tumour mass from DTC metastasis in the head of the favoured by the surgeons due to four previous operations pancreas leading to upper gastrointestinal bleeding with severe anaemia. 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 uneventful postoperative course. Histopathological performed. After the irradiation, the Tg level decreased examination revealed metastasis of the papillary thyroid continuously to a level of 17.2 ng/ml. One year after the cancer (Figure 2a) next to the papilla Vater lying in the irradiation, new cervical recurrence could be detected by head of the pancreas and confined by a capsule of imaging methods and the Tg level was 66.9 ng/ml. Due to the pancreatic tissue with growth into the muscularis propria radio-iodine non-responsive thyroid cancer, therapy with of the duodenum. Immunohistochemistry was positive for retinoids was started for redifferentiation of the tumour to Tg (Figure 2b). Postoperatively, the Tg level decreased to increase the radio-iodine uptake, but this therapy was 4.6 ng/ml. One year later, the Tg level had increased to stopped six months later due to severe side-effects. At the 14.2 ng/ml. New imaging revealed cervical tumour end of this treatment, restaging using cervical and thoracic recurrence and multiple metastases localised in the computed tomography (CT) showed stable cervical disease, and liver. Further therapy was refused by the patient. Two but the occurrence of a tumour localised at the right adrenal years later, a new metastasis in the former space of the gland. One month after completion of the redifferentiation right adrenal gland occurred with infiltration of the right therapy, the patient was admitted to hospital for severe kidney and compression of the inferior caval vein. Seven anaemia with a haemoglobin level of 6.2 g/dl. Apart from months later and 4ó years after the DP, the patient died pulmonary metastasis, thoracic and abdominal CT due to progressive abdominal metastatic spread. revealed a tumour of the right adrenal gland with a diameter of 6.5 cm. A biopsy of this tumour revealed Discussion adrenal metastasis of the DTC, therefore a right-sided adrenalectomy and resection of the tumour was carried Duodenal metastases are very uncommon, accounting for out. Histopathological examination showed metastases of 1% to 3% of all duodenal malignancies (1, 2), but they papillary thyroid cancer and the Tg level decreased to 28.1 should be taken into consideration in patients presenting ng/ml postoperatively. However, the anaemia persisted and with upper gastrointestinal bleeding and a previous history worsened. Two months later, when the patient needed of malignancy (3-5). The most common malignancies to daily units of blood due to unidentified bleeding, he was metastasise to the periampullary region occur either in the referred to our unit. A blood pool scintigraphy revealed colon, lung, breast or kidney, but there are scattered bleeding in the right lower abdomen; abdominal CT reports of metastases at other cancer sites (3, 6). In patients showed an enlarged pancreatic head (Figure 1) that had with DTC, distant metastases occur in 10%-20% of all not been detected in the previous CT scan performed for cases and are usually localised in the lung and (7). the adrenal metastasis. Upper gastrointestinal endoscopy Less common sites of metastases are the brain, liver and revealed a bleeding ulcer in the duodenum, and a biopsy skin. Occurrence of metastases at other sites, e.g., the showed metastasis from DTC. Because of the daily need duodenum, is exceptional. In our patient, the metastasis of for 2-4 units of blood, a resection of the metastasis was the DTC next to the papilla Vater with growth into the carried out using a partial PD Whipple-Kausch, with muscularis propria of the duodenum could be clearly

2270 Meyer and Behrend: Duodenopancreatectomy for Duodenal Metastasis identified by histopathological examination. However, in a (12-14). One of the most important factors affecting case report, ectopic microscopic thyroid follicles, localised mortality and morbidity is the emergence of specialised in the duodenum, have been reported with positive centres focussing on pancreatic surgery. Several recently immunoreaction for Tg (8). published series have revealed a distinct association For patients with metastatic DTC, radioactive iodine between high patient volumes and decreased mortality therapy is the gold standard for treatment and remains a rates (15-17). Today PD is also an accepted treatment for primary treatment modality, frequently offering the patient patients with benign such as chronic pancreatitis, several years of palliation. In the event of resistance to islet tumours and cystic neoplasms (14). radio-iodine ablation, the treatment is challenging. In the With this significant decrease in surgical complications, case of an isolated metastasis, surgery is one treatment the indications for this procedure may now be expanded to option in patients in good medical condition with low resection for metastatic disease to the periampullary region surgical risk offering the chance of cure. Stojadinovic et al. or to the pancreas. To date, only a few case reports and and Pak et al. demonstrated that a surgical approach with small series exist concerning the role of DP in metastatic metastasectomy in patients with well-differentiated but, in most of these reports, an aggressive surgical cancer was associated with improved survival on performing approach with DP was suggested for the management of a complete metastasectomy, and improvement of quality of these lesions (3, 5, 6, 18-20). Here, we present the first case life in cases of symptomatic distant metastasis when report of a resection of the head of the pancreas due to palliative resection was performed (9, 10). However, a bleeding metastasis of a papillary thyroid cancer. A median surgical approach can also be indicated in the case of a survival of 23-26 months can be achieved with good symptomatic metastasis for rapid amelioration of disorders, palliation, with a 5-year survival of 17% (3, 6, 20). Indeed, even in patients with multiple metastases, as in the case of our patient survived for more than 4 years after the DP. In our patient to stop the bleeding. contrast, the median survival for for all Although surgical resections of metastatic lesions of the patient groups reported in the literature ranges between liver, lung and brain have proved to be useful, the role of only 12 months and 18 months, with a 5-year survival rate surgical resection in the case of a solitary metastatic or of approximately 5%-15% (12, 21-23). Therefore, a survival locally recurrent malignancy in the duodenal or rate can be achieved that is at least as good as that for periampullary region has not yet been defined. Previous patients with a primary periampullary carcinoma. reports have advocated a conservative approach for Additionally, the DP used in our patient was the only periampullary metastatic lesions, because of the historically method for treating the severe anaemia with a satisfactory high rates of perioperative morbidity and mortality of DP and long-lasting effect. Therefore, we believe that surgery, in patients with primary pancreatic adenocarcinoma on the although an aggressive therapy, should remain a viable one hand, and the expected short survival time in patients treatment option for carefully selected patients, even with with multiple metastases on the other. For many years, this palliative intent. procedure was characterised as a difficult, hazardous and To summarise, from this case report and from the few somewhat questionable procedure, associated with high cases documented in the literature, it can be concluded that morbidity rates exceeding 60% and mortality rates DP for metastatic disease can be considered in selected approaching 25%. This has led to a reluctance to treat patients for alleviation of the symptoms and prolongation of these metastases with DP (11). However, during the past survival, as long as this operation is performed by two decades, the results from this procedure have gradually experienced surgeons who can achieve minimal morbidity improved, and the Whipple operation and its modifications and mortality. have evolved as safe and effective procedures for several indications. In addition to advances in surgical techniques References and a better understanding of pancreatic diseases, 1 Farmer RG and Hawk WA: Metastatic tumours of the small numerous improvements in diagnostic and interventional bowel. Gastroenterology 47: 496-504, 1964. radiology, surgical techniques, intensive and perioperative 2 Kadakia SC, Parker A and Canales L: Metastatic tumors to the care and management of complications have contributed to upper gastrointestinal tract: endoscopic experience. Am J the currently low mortality of DP (12). In recent years, the Gastroenterol 87: 1418-1423, 1992. operative mortality for DP has dramatically decreased, with 3 Le Borgne J, Partensky C, Glemain P, Dupas B and de mortality rates of less than 5%. Today the reported major Kerviller B: Pancreaticoduodenectomy for metastatic ampullary and pancreatic tumors. Hepatogastroenterology 47: causes for postoperative mortality are intra-abdominal 540-544, 2000. bleeding, sepsis related to pancreaticojejunal anastomotic 4 Cremon C, Barbara G, De Giorgio R et al: Upper leakage and cardiopulmonary failure. Although the quoted gastrointestinal bleeding due to duodenal metastasis from morbidity rate has also decreased, it is still around 40% primary lung carcinoma. Dig Liver Dis 34: 141-143, 2002.

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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.

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5 Loualidi A, Spooren PF, Grubben MJ, Blomjous CE and Goey 16 Neoptolemos JP, Russell RC, Bramhall S and Theis B: Low SH: Duodenal metastasis: an uncommon cause of occult small mortality following resection for pancreatic and periampullary intestinal bleeding. Neth J Med 62: 201-205, 2004. tumours in 1026 patients: UK survey of specialist pancreatic units. 6 Nakeeb A, Lillemoe KD and Cameron JL: The role of UK Pancreatic Cancer Group. Br J Surg 84: 1370-1376, 1997. pancreaticoduodenectomy for locally recurrent or metastatic 17 Sosa JA, Bowman HM, Gordon TA et al: Importance of carcinoma to the periampullary region. J Am Coll Surg 180: hospital volume in the overall management of pancreatic 188-192, 1995. cancer. Ann Surg 228: 429-438, 1998. 7 Leger AF: Distant metastasis of differentiated thyroid . 18 Medina-Franco H, Halpern NB and Aldrete JS: Diagnosis by 131 iodine (I 131) and treatment. Ann Endocrinol Pancreaticoduodenectomy for metastatic tumors to the 56: 205-208, 1995. periampullary region. J Gastrointest Surg 3: 119-122, 1999. 8 Takahashi T, Ishikura H, Kato H, Tanabe T and Yoshiki T: 19 Wagle PK, Katrak MP, Navadgi SM, Tapia AA and Joshi RM: Ectopic thyroid follicles in the submucosa of the duodenum. Pancreaticoduodenectomy for metastatic colonic cancer – Virchows Arch A Pathol Anat Histopathol 418: 547-550, 1991. report of two cases. Indian J Gastroenterol 20: 68-69, 2001. 9 Stojadinovic A, Shoup M, Ghossein RA et al: The role of 20 Sperti C, Pasquali C, Liessi G, Pinciroli L, Decet G and operations for distantly metastatic well-differentiated thyroid Pedrazzoli S: Pancreatic resection for metastatic tumors to the carcinoma. Surgery 131: 636-643, 2002. pancreas. J Surg Oncol 83: 161-166, 2003. 10 Pak H, Gourgiotis L, Chang WI et al: Role of metastasectomy 21 Conlon KC, Klimstra DS and Brennan MF: Long-term survival in the management of thyroid carcinoma: the NIH experience. after curative resection for pancreatic ductal adenocarcinoma. J Surg Oncol 82: 10-18, 2003. Clinicopathologic analysis of 5-year survivors. Ann Surg 223: 11 Roland CF and van Heerden JA: Nonpancreatic primary 273-279, 1996. tumors with metastasis to the pancreas. Surg Gynecol Obstet 22 Kuvshinoff BW and Bryer MP: Treatment of resectable and 168: 345-347, 1989. locally advanced pancreatic cancer. Cancer Control 7: 428-436, 12 Schafer M, Mullhaupt B and Clavien PA: Evidence-based 2000. pancreatic head resection for pancreatic cancer and chronic 23 Bradley EL III: Pancreatoduodenectomy for pancreatic pancreatitis. Ann Surg 236: 137-148, 2002. adenocarcinoma: triumph, triumphalism, or transition? Arch 13 Strasberg SM, Drebin JA and Soper NJ: Evolution and current Surg 137: 771-773, 2002. status of the Whipple procedure: an update for gastroenterologists. Gastroenterology 113: 983-994, 1997. 14 Schmidt CM, Powell ES, Yiannoutsos CT et al: Pancreatico- duodenectomy: a 20-year experience in 516 patients. Arch Surg 139: 718-725, 2004. 15 Lieberman MD, Kilburn H, Lindsey M and Brennan MF: Relation of perioperative deaths to hospital volume among patients undergoing pancreatic resection for malignancy. Ann Received November 30, 2005 Surg 222: 638-645, 1995. Accepted January 19, 2006

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