Pancreaticoduodenectomy for the Management of Pancreatic or Duodenal Metastases from Primary Sarcoma

Results

Seven patients, one male and six female, underwent pancreaticoduodenectomy for sarcoma metastases. The median age was 59 years (range=19-73 years). Two patients had primary retroperitoneal well-differentiated and dedifferentiated liposarcomas. One patient had metastatic osteosarcoma from the femur and the other four all had a histopathological diagnosis of leiomyosarcoma, which ranged from low-to high-grade tumours. Of these, the primary site varied, and included two primary uterine sarcomas, one tumour from the broad ligament, and one that originated in the inferior vena cava. In only one case was the disease pancreas-sparing, affecting only the duodenum (Table I).

One patient had a diagnosis of retroperitoneal liposarcoma with synchronous pancreatic metastases requiring subtotal gastrectomy, pancreaticoduodenectomy, right hemicolectomy, cholecystectomy and excision of two abdominal sarcomatous masses. Six patients had had their primary tumour resected prior to the diagnosis of their pancreatic metastases.

Two patients presented with pancreatico-duodenal metastasis as the first site of disease recurrence. One of these patients had a leiomyosarcoma of the inferior vena cava, and presented with anaemia and abdominal pains after a disease-free interval (DFI) of 40 months following resection of the primary tumour. She underwent an upper gastrointestinal endoscopy that demonstrated a mucosal tumour in the second part of the duodenum and which on computed tomographic (CT) imaging appeared to be a metastasis within the pancreas eroding into the duodenum. However, postoperative histology demonstrated that the recurrence was limited to the duodenal wall. In the other six patients, metastases originated within the pancreatic parenchyma. The other patient in this group had a dedifferentiated retroperitoneal liposarcoma, and presented with abdominal discomfort, radiating through to the left side of his back after a DFI of 7 years post resection of the primary, which had included an en-bloc resection of the left kidney.

There were four patients who had had a diagnosis of extra-pancreatic sarcoma recurrence prior to the pancreatic metastasis. Three of these patients had leiomyosarcoma histology and one had femoral osteosarcoma. The first patient in this group had high-grade leiomyosarcoma of the broad ligament and developed recurrence in the lung and chest wall 7 months following initial management. The lung deposits responded well to chemotherapy with six cycles of doxorubicin and ifosfamide. Eleven months later, lung metastases were found on surveillance and these were treated with metastectomy of two lung lesions with perioperative gemcitabine and docetaxel to complete remission. Subsequently, there was a 16-month disease-free interval before further metastases in the original abdominal incision. As work-up for further resection a positron emission tomographic (PET) scan showed increased uptake in the region of the duodenum and pancreas. Laparotomy was performed and intra-operatively, this tumour was found to be protruding into the peritoneal cavity but was covered with peritoneum and omentum. Further disease was noted in the retroperitoneum and excised. In addition, a small tumour was felt at the head of the pancreas and a core needle biopsy was undertaken. Histology confirmed metastatic leiomyosarcoma. Four months after this laparotomy, the patient underwent pancreaticoduodenectomy from which she recovered well. However, on postoperative surveillance imaging 7 months following this surgery, she was noted to have progressive disease in the lungs, pelvis and paraspinal region and commenced on gemcitabine and docetaxel. Nineteen months following the pancreaticoduodenectomy she presented with small bowel obstruction and underwent laparotomy, limited right hemicolectomy and sigmoid colectomy. The histology of the mesenteric mass causing the obstruction was confirmed to be metastatic leiomyosarcoma. The patient died from progressive disease at 47 months following the pancreatoduodenectomy.

Another patient originally presenting with uterine leiomyosarcoma developed pulmonary metastases 17 years after resection of the primary disease. This was managed with a right upper lobectomy, followed by radiotherapy in view of the involved resection margins on histopathological examination. Two years later, she developed epigastric pain and a PET scan demonstrated recurrence at the head of the pancreas. She underwent pylorus-preserving pancreaticoduodenectomy and superior mesenteric vein resection and reconstruction. Histological examination confirmed metastatic leiomyosarcoma. At 11 months following resection, the patient experienced recurrence with a right maxillary mass involving the orbital apex floor and received a further three cycles of docetaxel and gemcitabine. However, she died 15 months postoperatively due to Escherichia coli-associated septicaemia.

The third patient had multiple disease recurrence following her resection of a high-grade leiomyosarcoma of the uterus. She had no adjuvant treatment at the time of the original resection. At 16 months, she developed a maxillary recurrence, with suspicion of a small pulmonary nodule and pelvic lymph node. She underwent surgical macroscopic resection of the maxilla followed by radical radiotherapy. In view of her progressive metastatic disease and the slow growth of her lung nodules, a watch-and-wait strategy was adopted. Her disease progressed 1 month later in the pelvis, prompting a laparotomy and microscopic complete resection. Again, she underwent postoperative radiotherapy but recurrence occurred 5 months on with a pathological fracture of the left humerus. This was managed with surgical excision and reconstruction followed by further radiotherapy to the humerus. Six months later, this patient had emergency presentation with malaena. Upper gastrointestinal endoscopy demonstrated an obstructing lesion in the duodenum that was histologically proven to be metastatic leiomyosarcoma. Imaging by CT scan demonstrated a 6×7 cm mass involving the pancreatic head and medial wall of the duodenum wall. There was obstruction of the duodenum lumen and evidence of extrahepatic bile duct dilatation. Of note, the CT scan demonstrated no progression of the lung nodules over 18 months. Following resuscitation and stabilisation, an expedited pancreaticoduodenectomy was undertaken for continued bleeding from the metastasis. Four months following surgery, the patient developed further metastatic disease in the right 4th rib and was given further radiotherapy. One month later chemotherapy was administered for progressive disease in the lungs and pelvis. The patient died 21 months after pancreaticoduodenectomy.

The fourth patient was a 19-year-old female who was initially diagnosed with osteosarcoma of the distal femur. She was treated initially with cisplatin and doxorubicin, which was switched to ifosfamide, etoposide and methotrexate due to cardiotoxicity. She underwent resection of the primary tumour with prosthesis and subsequently enrolled in the 105AD7 osteosarcoma vaccine trial. Fifty-nine months following diagnosis, this patient developed pulmonary metastases, which were originally thought to be unresectable. However, following a partial response to carboplatin and etoposide, she underwent surgical resection of the pulmonary metastases. Sixty-six months following diagnosis, she developed anaemia and was found on imaging to have a 5-cm pancreatic mass invading the duodenum and underwent urgent pancreaticoduodenectomy. The histology confirmed metastatic osteosarcoma in the pancreas. She underwent a further laparotomy 1 month post pancreatoduodenectomy due to adhesional obstruction and was commenced on adjuvant doxorubicin and methotrexate. Unfortunately, she developed metastases in the porta hepatis, liver and peritoneum 20 months postoperatively and died 4 months later.

There was one perioperative mortality giving an overall pancreatoduodenectomy perioperative mortality rate of 1.5% for the period 2006-2016. This was the only male in the series and the tumour encased the superior mesenteric pedicle. Bleeding was encountered during the dissection around the mesenteric vessels. Difficulty was encountered in securing haemostasis and the abdomen required packing, with a plan for removal after 48 hours. On return to the Intensive Care Unit, the patient had respiratory deterioration, escalating inotrope requirements and died from a massive pulmonary embolus.

All six patients that survived the perioperative period had disease recurrence, with a median DFI of 11 months (range=4-27 months). These patients all had intermediate-high-grade (grade 2-3) tumours. Median overall survival was 21 months (range=4 days to 86 months) from pancreatoduodenectomy.