Abstract
Liver metastases from adrenocortical carcinoma are very rare and no clear indications for surgery exist. The aim of the present work was to define surgical indications for these neoplasms. All the patients submitted to hepatic resection for liver metastases from adrenal carcinoma reported in the literature (PubMed source) from 1978 to 2005 were considered for the present study. Forty-eight patients were found in the period of study, but it was only possible to obtain certain data for nine patients (18.7%). The data investigated suggest that metachronous metastases, developed after a minimum of 1 year from the primary tumor, and completely removable, may represent an indication for surgery – although this still needs to be proved.
Keywords: Liver metastases, adrenocortical carcinoma, hepatic surgery
Introduction
With an incidence of 0.5–2 cases per million population each year, adrenocortical carcinoma represents a very rare tumor 1. Isolated liver metastases are even more rare, since only about 50 cases have been reported in the literature. The majority of these cases have been comprehensively discussed in association with other noncolorectal nonneuroendocrine liver metastases.
The aim of this study was to analyze exclusively liver metastases from adrenal carcinoma in order to determine indications for surgery.
Patients and methods
All the patients submitted to hepatic resection for liver metastases from adrenal carcinoma reported in literature (PubMed source) from 1978 to 2005 were considered for the present study. The following details were considered for each publication: the number of patients, sex, age, time of metastases presentation in relation to primary tumor, number of metastases, size of the tumor, localization in the liver, extent of resection (according to Couinaud 2 classification of minor hepatic resection is defined as less than two segments, major hepatic resection as three or more segments), adjuvant chemotherapeutic treatment, disease-free interval (DFI), survival after liver resection and outcome. Literature with incomplete data was investigated by an e-mail request addressed to the authors of the original reports.
Results
Patients considered for this study are listed in Table I3,4,5,6,7,8,9,10,11,12,13,14,15. Forty-eight patients were found in the period of study, but it was only possible to obtain certain data for nine patients (18.7%).
Table I. Liver metastases from adrenocortical carcinoma reported in the literature*.
| References | Year | Number of patients | Sex | Age (years) | Time from primary tumor | Number of metastases | Site | Size (cm) | Extension of resection | Chemotherapy | DFI | Survival | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Foster 3 | 1978 | 2 | – | – | – | – | – | – | |||||
| Cobourn et al. 4 | 1987 | 2 | – | – | – | – | – | – | |||||
| Iwatsuki & Starzl 5 | 1988 | 4 | – | – | – | – | – | – | |||||
| Harrison et al. 6 | 1997 | 7 | – | – | – | – | – | – | |||||
| Berney et al. 7 | 1998 | 1 | Female | 27 | Met (36 months) | 2 | Segment 4 | 2.8–6 | Minor | Yes (mitotane) | 135 months | 135 months | Alive |
| Lang et al. 8 | 1999 | 6 | – | – | – | – | – | – | |||||
| Hemming et al. 9 | 2000 | 3 | – | – | – | – | – | – | |||||
| Laurent et al. 10 | 2001 | 1 | Met (22 months) | – | Bilobar | – | 42 months | Dead | |||||
| Langer et al. 11 | 2000 | 2 | Syn | 1 | – | Minor | 1 months | Dead | |||||
| Met | 1 | – | minor | 4 months | Dead | ||||||||
| Williams et al. 12 | 2002 | 1 | Met (20 months) | 3 | Bilobar | 9, 7, 5, respectively | Major | No | 18 months | 27 months | Dead | ||
| Di Carlo et al. 13 | 2004 | 1 | Female | 32 | Met (36 months) | 1 | Segment 6 | 7 | Minor | No | 38 months | 38 months | Alive |
| Weitz et al. 14 | 2005 | 15 | |||||||||||
| Ercolani et al. 15 | 2005 | 3 | Male | 18 | Syn | 4 | 12 | – | 11 months | Dead | |||
| Male | 22 | Met (6 months) | 6 | Right lobe | 7 | Major | No | 6 months | 10 months | Dead | |||
| Male | 51 | Syn | 3 | 5 | – | 6 months | Dead | ||||||
| Total number of patients | 48 |
syn, synchronous; met, metachronous; DFI, disease-free interval.
*Search of PubMed.
A case of a female patient aged 36 years, affected by adrenal carcinoma and developing a single liver metastasis 3 years after primary tumor resection, has been reported by our group 13. The lesion was located in segment 6 of the liver and a segmentectomy was performed. The patient is alive without any relapse. No chemotherapy has been administered.
Williams et al. reported the case of a male patient submitted to a two-stage subtotal hepatectomy 20 months after an adrenalectomy for bilobar liver metastases 12. A metastasis of 9 cm in diameter was located in the left lobe, and two lesions, measuring 7 and 5 cm, respectively, in the right lobe. A right hemihepatectomy and cryotherapy to the left lobe were performed at the first step; 4 months later the patient was submitted to a left lobectomy including the mass treated with cryotherapy. The patient was free from disease for 18 months, but he died 2 years and 3 months after the initial liver resection. The cause of death is not specified in the manuscript.
Langer et al. report the cases of two patients affected by hepatic metastases from adrenal carcinoma 11. In one patient the metastasis was synchronous, so adrenalectomy, nephrectomy and resection of liver metastasis were performed at the same time. This patient died 1 month after surgical treatment. The second patient, after resection of primary tumor, developed a local recurrence and liver metastasis that were both resected, but the patient survived only 4 months. The single case reported by Berney et al. 7 has experienced an excellent survival of 135 months. In contrast, the patients in the report by Ercolani et al. had a poor outcome 15. These patients were affected by synchronous metastases or had a limited DFI between the primary tumor and the liver metastases.
The remaining patients presented in the literature are reported comprehensively with other kinds of tumor, and data are incomplete.
Discussion
Adrenal carcinoma is a rare malignancy with a poor prognosis. Different reports have been published with different conclusions about the appropriate treatment of this tumor. However, the basis of any treatment is the complete surgical ablation of the tumor and of the local or metastatic recurrence. Hepatic metastases from adrenal carcinoma are very rare and concern the field of noncolorectal nonneuroendocrine metastases.
The presented data are limited and details of only a few of these cases are complete. We have contacted the authors of the recent reports but, due to moving to other hospitals and consequent lack of access to the old data 8, or no reply to our requests 6,9, some reported cases remain incomplete. Of the data reported in the present study the best results were achieved in patients with metachronous metastases developed after a disease-free survival >1 year in which a complete resection was performed. The patients with synchronous metastases had poor results, recurrence occurred rapidly and the survival was short.
Surgery is the only choice of treatment for metastatic disease, because there is no definitive protocol for chemotherapy, and although therapy with mitotane is commonly used, its therapeutic value, alone or in combination with other chemotherapeutic agents, is still very controversial. In fact, the use of mitotane after surgical resection, as recommended by some authors, to improve the survival, has not been proved to be effective 1,16. Cryotherapy has been reported as a bridging therapy to prevent progression of the remaining tumor, in order to perform a two-stage subtotal hepatectomy for multiple metastases from adrenal carcinoma 12.
In conclusion, no guidelines can be given, but this study suggests that metachronous metastases, developed after a minimum of 1 year from the primary tumor, and completely removable, may represent an indication for surgery, although this has still to be proved. Cryotherapy or radiofrequency ablation can be used to make the metastases resectable.
Acknowledgments
Special thanks to Dr G. Ercolani, University of Bologna (Italy), Dr C. Laurent, University of Bordeaux (France), and Professor G. Mentha, University of Geneva (Switzerland) for providing me with the requested data which were not contained in their published works. I am indebted to Dr F. Barbagallo for revising the English language of the manuscript.
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