Adrenal cortical carcinoma is a rare cancer that often presents in an advanced stage. Not only systemic metastases but also local recurrence and peritoneal metastases prevent long-term survival in these patients.
A profoundly symptomatic patient with extensive peritoneal metastases and local recurrence was treated using cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with melphalan as the chemotherapy agent.
Relative sparing of the small bowel within the abdomen and pelvis allowed a visible complete resection of all cancer. The HIPEC with melphalan was used to control microscopic residual disease. Similar surgical technology used in this patient could be used to prevent local recurrence and peritoneal metastases in patients at the time of resection of the primary adrenal cortical carcinoma.
Rare diseases may have peritoneal metastases as a component of disease progression and profit from treatment with CRS plus HIPEC. The clinical features suggesting a favorable outcome from this combined treatment are relative sparing of small bowel and its mesentery, absence of disease outside the abdomen, low-grade disease, or limited extent of high-grade disease.
Tumori 2016; 102(6): 588 - 592
Article Type: ORIGINAL RESEARCH ARTICLE
AuthorsPaul H. Sugarbaker
- • Accepted on 01/09/2016
- • Available online on 27/09/2016
- • Published in print on 01/12/2016
This article is available as full text PDF.
Initial success with the potentially curative treatment of peritoneal metastases occurred with low-grade appendiceal mucinous neoplasms causing the pseudomyxoma peritonei syndrome (1). Cytoreductive surgery (CRS) plus perioperative intraperitoneal chemotherapy is now the global standard of care for this rare disease (2). This management plan has been used to treat peritoneal metastases from more common malignancies with peritoneal dissemination such as colorectal cancer, gastric cancer, and ovarian cancer (3-4-5). However, rare abdominal and pelvic malignancies that produce peritoneal metastases have been successfully treated using this management strategy (6). Adrenal cortical carcinoma is one of these rare cancers that progress with local recurrence and peritoneal metastases in approximately 50% of patients (7). In this report, we describe the management of a patient with a large extent of local recurrence plus peritoneal metastases of adrenal cortical carcinoma. Complete CRS plus hyperthermic intraperitoneal melphalan was used to produce a short-term favorable outcome. A literature review of other unusual diseases treated by CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) follows. Our goal is to define the selection criteria for patients with peritoneal metastases from rare diseases for this comprehensive treatment strategy.
In December 2015, a 31-year-old woman presented with abdominal pain from progressive peritoneal metastases from metastatic adrenal cortical carcinoma. Her medical history revealed back pain beginning in September 2013. In March 2014, the pain suddenly increased and abdominal distention was first noted. Computed tomography (CT) showed a large right-sided hepatic malignancy thought to be a hepatocellular carcinoma. On April 9, 2014, a right hepatectomy and right adrenalectomy were performed. Pathology showed an unexpected adrenal cortical carcinoma with extensive invasion into the right liver. Postoperative radiation to the adrenal resection site was performed. From September 2014 through February 2015, the patient received systemic chemotherapy. In May 2015, an open and close surgical procedure was performed and the widespread peritoneal metastases were considerably unresectable. On July 7, 2015, a debulking procedure to remove the greater omentum was performed and hyperthermic intraperitoneal cisplatin was used. This palliative procedure resulted in approximately 5 months of benefit.
Computed tomography on December 8, 2015, showed a 6-cm pleural mass medially and inferiorly in the right thorax. More than half of the right kidney was destroyed by the mass. Small bowel was not dilated. It was compartmentalized in the right mid and lower abdomen by large cancerous masses. Below the umbilicus, no small bowel was visible on CT, but the colon and rectum were not dilated. Tumor masses surrounded the bladder but there was no ureteral obstruction (see
Computed tomography slices through the abdomen and pelvis show the distribution of an advanced peritoneal dissemination of an adrenocortical carcinoma.
On December 30, 2015, the patient underwent a 13-hour cytoreduction that included a right nephrectomy and partial resection of the right hemidiaphragm and pleural mass, hysterectomy and bilateral salpingo-oophorectomy, pelvic peritonectomy, and left colectomy with low anastomosis (
Intraoperative photograph. The large masses of tumor fill the pelvis and left side of the abdomen. The small bowel is compartmentalized in the right side of the abdomen and neither small bowel nor transverse colon show bowel obstruction.
Computed tomography performed on April 23, 2016, showed a new mass lesion in the left adrenal gland. Magnetic resonance imaging on June 3, 2016, confirmed that the mass had rapidly expanded to 9.8 5.0 6.7 cm. With a preoperative diagnosis of second primary adrenal cortical carcinoma, the patient underwent exploratory laparotomy and left adrenalectomy on June 29, 2016. There was no evidence of peritoneal metastases and there was an R0 resection of the left adrenal cortical carcinoma with adjuvant melphalan at 50 mg/m2 at 42°C for 60 minutes. She was discharged on postoperative day 5. Her current performance status is 0 and she is clinically disease-free.
Adrenocortical carcinoma has not been previously identified as a malignancy appropriate for treatment by CRS plus HIPEC. Elias (9), in a personal communication, described 4 patients, 3 of whom had died, and concluded that complete cytoreduction may be of benefit in selected cases but that HIPEC is unlikely to be of benefit because of chemotherapy resistance of the tumor. Hughes et al have generated a protocol for treatment of peritoneal metastases from adrenocortical carcinoma but as yet no publications have been forthcoming (10). Our patient had a complete resection of a very large volume of disease followed by HIPEC with melphalan. Her short-term outcome (palliation) has been excellent as a result of the complete visible removal of abdominal and pelvic cancer. Longer follow-up is necessary before any conclusions concerning maintenance of the complete cytoreduction by melphalan can occur.
The natural history of adrenocortical carcinoma suggests that surgical technology to improve local control of the primary malignancy may result in improved outcomes with this disease process. In 2010, Leboulleux et al (11) reported a 27% incidence of peritoneal metastases in 58 patients treated by open surgery. In 6 patients resected by laparoscopic surgery, the incidence of peritoneal metastases was 67%. In 2012, Miller et al (12) reported on 110 open resections with a 16% incidence of peritoneal metastases. In 56 laparoscopic resections, the incidence of peritoneal metastases was 30%. Likewise, in 2012, Lombardi et al (13) published a multi-institutional study of 126 open resections with a 19% incidence of peritoneal metastases. Thirty laparoscopic resections were reported with a 21% incidence of peritoneal metastases.
In 2016, Amini et al (7) gathered information on 180 patients from 13 institutions who had a potentially curative resection of adrenocortical carcinoma. Two-thirds of the patients experienced disease recurrence. This was local only in 36.3%, distant only in 45.1%, and combined local-regional and distant in 18.6%. Increasing T-stage was associated with local-regional recurrence (p = 0.02). Margonis et al (14) reported that the surgical margin status had an impact on long-term outcomes. An R0 resection was achieved in 126 patients (76.4%) and R1 resection in 39 (23.6%). Median and 5-year overall survival for patients undergoing R0 resection were 96.3 months and 64.8% as compared to 25.1 months and 33.8% for patients having an R1 resection (p<0.001). The authors concluded that an emphasis on surgical technique to achieve an R0 margin of resection was crucial to optimizing long-term survival.
The high incidence of local-regional recurrence and peritoneal metastases in adrenocortical carcinoma patients suggests that additional surgical technology is required to optimize the primary resection of these patients. Local-regional failure including peritoneal metastases was reported to be 16% to 67% depending on the institution and the method of resection (open vs laparoscopic). No reports that describe treatments or results of treatment for local-regional or metastatic disease were available. This report of CRS plus hyperthermic intraperitoneal melphalan as a possible approach to peritoneal metastases from this disease is the first in the literature.
Adrenal cortical carcinoma is one of many rare diseases that cause peritoneal metastases. Many of these rare diseases manifest peritoneal metastases that have been successfully treated by CRS and HIPEC (6). Urachal adenocarcinoma with peritoneal metastases, ovarian teratoma with peritoneal metastases, and small bowel adenocarcinoma with peritoneal metastases are a few with accompanying literature.
Rare diseases having isolated peritoneal metastases and possibly treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
|Low malignant potential ovarian tumors|
|Colonic polyps (traumatic resection)|
|Desmoplastic small round cell tumor|
|Endocervical mucinous adenocarcinoma|
|Fibrolamellar hepatocellular carcinoma|
|Germ cell testicular tumor|
|Frantz pseudopapillary tumor of the pancreas|
|Adenocarcinoma of unknown primary site (normal appendix identified)|
An important consideration of this new concept in management of peritoneal metastases from rare diseases is the selection process. The surgeon wishes to perform CRS and HIPEC on those patients who are likely to profit and who have an acceptable morbidity and mortality that accompanies these treatments. All or almost all diseases within the abdomen and pelvis must be removed by peritonectomy procedures and visceral resections (1, 6). The radiologic evaluation should show a relative sparing of small bowel and small bowel mesentery of metastatic disease. Also, there should be no metastases in the lungs or distant lymph nodes. If hepatic metastases are present, they should be of limited extent and resectable without major parenchymal liver resection. High-grade disease intimately associated with the porta hepatis is rarely resectable (15, 16). If the malignancy is aggressive, only a small or moderate peritoneal cancer index may be present (17). The top portion of
Clinical features suggesting a favorable outcome for use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal metastases from rare diseases and clinical features suggesting cytoreductive surgery and hyperthermic intraperitoneal chemotherapy should not be recommended
|Clinical features suggesting a favorable outcome|
|1. General medical condition compatible with survival and recovery from the procedure.|
|2. Clinical information regarding the peritoneal metastases compatible with a complete or near complete cytoreduction.|
|a. Relative sparing of the small bowel and colon.|
|b. Absence of disease outside the abdomen/pelvis.|
|c. If hepatic metastases are present, they are limited, compatible with wedge resection.|
|d. Absence of disease within the porta hepatis.|
|3. With a high-grade malignancy, a low or moderate peritoneal cancer index.|
|4. Symptomatic patient.|
|Clinical features suggesting an unfavorable outcome|
|1. Poor performance status.|
|2. Rapid progression of a high-grade disease process.|
|3. Low likelihood of a response to perioperative chemotherapy.|
|4. Prior abdominal or pelvic radiation therapy.|
|5. Asymptomatic from peritoneal metastases.|
Sugarbaker PH Management of unusual abdominal and pelvic neoplasms with peritoneal dissemination: Case reports and literature review. (In) Sugarbaker PH (Ed). Cytoreductive Surgery & Perioperative Chemotherapy for Peritoneal Surface Malignancy. Textbook and Video Atlas. Cine-Med Publishing: Woodbury, CT, 2012, pp. 137-158.