Adrenocortical carcinoma surgery: Difference between revisions

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{{Adrenocortical carcinoma}}
{{Adrenocortical carcinoma}}
{{CMG}}; {{AE}} {{RT}}
{{CMG}}; {{AE}} {{RT}} {{MAD}}
==Overview==
==Overview==
Surgery is the mainstay of treatment for adrenocortical carcinoma.
[[Surgery]] is the mainstay of treatment for adrenocortical carcinoma. Appropriate [[preoperative evaluation]] and operative planning are really important to assure the best outcome. [[Lymph nodes]] should be removed as part of the en bloc [[resection]].  Recurrence in the [[peritoneum]] outside the tumor bed has the worst survival. [[Surgery]] is indicated in those patients with [[disease]] confined to one site or [[Organ (anatomy)|organ]].
==Surgery==
==Surgery==
*Surgery is the mainstay of treatment for adrenocortical carcinoma.
*[[Surgery]] is the mainstay of treatment for adrenocortical carcinoma.
*Surgery can also be performed even in the case of the invasion into large blood vessels, such as the [[renal vein]] or [[inferior vena cava]].
*[[Adrenalectomy]] can also be performed even in the case of the [[invasion]] into large [[blood vessels]], such as the [[renal vein]] or [[inferior vena cava]].
*A large percentage of patients are not surgical candidates.
*A large percentage of patients are not surgical candidates.
Appropriate preoperative evaluation and operative planning are the most important to assure the best outcome.  
*Appropriate preoperative evaluation and operative planning are the most important to assure the best outcome.
*Preoperative imaging should be obtained to evaluate the extent of the [[tumor]].
*[[Imaging]] should be done just before the [[surgery]] because ACC grow quickly and involvement of adjacent structures may change.
*Optimization of [[hormone]] excess in patients with functional [[Mass|masses]] especially those with [[Cushing's syndrome|Cushing’s syndrome]] should be done.
*Patients with widespread distant [[Metastasis|metastatic]] disease in multiple [[organs]] or those with multiple [[metastatic]] deposits in one [[Organ (anatomy)|organ]] system, unable to be completely resected, should not undergo [[adrenalectomy]]. The primary [[tumor]] can instead be treated with [[External beam radiotherapy|external beam radiation]] for [[Palliative care|palliation]] along with other adjuncts to improve local [[symptoms]] and for better control of [[hormone]] excess, if present.<ref name="pmid20675074">{{cite journal| author=Sabolch A, Feng M, Griffith K, Hammer G, Doherty G, Ben-Josef E| title=Adjuvant and definitive radiotherapy for adrenocortical carcinoma. | journal=Int J Radiat Oncol Biol Phys | year= 2011 | volume= 80 | issue= 5 | pages= 1477-84 | pmid=20675074 | doi=10.1016/j.ijrobp.2010.04.030 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20675074  }}</ref>
*[[Obstruction]] of the [[Inferior vena cava|vena cava]] by [[tumor]] [[thrombus]] can lead to massive lower extremity [[edema]]. If [[tumor]] [[resection]] is not technically operable, [[Vena cavae|vena cava]] [[stents]] can be placed, leading to temporary prevention of [[occlusion]].
*[[Debulking]] for control of [[hormone]] excess in the setting of known [[Metastasis|metastatic]] disease is also performed in some situations. The benefits of [[debulking]] must outweigh the risks of [[surgery]] in patients who have [[Wound healing phases|poor wound healing]].


Preoperative imaging should be obtained to evaluate the extent of the tumor.
* [[Lymph nodes]] should be removed as part of the en bloc [[resection]]. The [[lymphadenectomy]] is performed based on the [[arterial]] supply of [[Adrenal mass causes|adrenal tumors]].<ref name="pmid22306837">{{cite journal| author=Gaujoux S, Brennan MF| title=Recommendation for standardized surgical management of primary adrenocortical carcinoma. | journal=Surgery | year= 2012 | volume= 152 | issue= 1 | pages= 123-32 | pmid=22306837 | doi=10.1016/j.surg.2011.09.030 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22306837  }}</ref>
* Risk of severe [[bleeding]] and benefits of massive removal of [[Lymph node|lymph nodes]] should be balanced by surgeons in every case.<ref name="pmid22143204">{{cite journal| author=Reibetanz J, Jurowich C, Erdogan I, Nies C, Rayes N, Dralle H et al.| title=Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma. | journal=Ann Surg | year= 2012 | volume= 255 | issue= 2 | pages= 363-9 | pmid=22143204 | doi=10.1097/SLA.0b013e3182367ac3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22143204  }}</ref>
* Published data comparing the [[efficacy]] of [[laparoscopic]] [[adrenalectomy]] (LA) vs open [[adrenalectomy]] (OA) for ACC are limited.
{| class="wikitable"
![[Laparoscopic surgery|Laparoscopic]] [[adrenalectomy]] (LA)
!Open [[adrenalectomy]] (OA)
|-
|
* LA, when compared with open [[adrenalectomy]] has shown:
** Lower [[morbidity]] 
** Less [[pain]] 
** Shorter hospital stays
** Decreased recovery time if compared with open [[adrenalectomy]].
* Application of [[laparoscopic]] instruments can result in the shedding of [[malignant]] [[cells]].<ref name="pmid23158185">{{cite journal| author=Miller BS, Gauger PG, Hammer GD, Doherty GM| title=Resection of adrenocortical carcinoma is less complete and local recurrence occurs sooner and more often after laparoscopic adrenalectomy than after open adrenalectomy. | journal=Surgery | year= 2012 | volume= 152 | issue= 6 | pages= 1150-7 | pmid=23158185 | doi=10.1016/j.surg.2012.08.024 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23158185  }}</ref>
* Recurrence and [[Peritoneal|peritonea]]<nowiki/>l spread were more common in the LA group.<ref name="pmid16360394">{{cite journal| author=Gonzalez RJ, Shapiro S, Sarlis N, Vassilopoulou-Sellin R, Perrier ND, Evans DB et al.| title=Laparoscopic resection of adrenal cortical carcinoma: a cautionary note. | journal=Surgery | year= 2005 | volume= 138 | issue= 6 | pages= 1078-85; discussion 1085-6 | pmid=16360394 | doi=10.1016/j.surg.2005.09.012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16360394  }}</ref>
* Higher [[incidence]] of incomplete [[Resection|resections]] is found in LA.
* [[Peritoneal carcinomatosis]] ([[Spread of the cancer|spread]]) occurred in only 25% of cases.
* Recurrence rate is 100%.<ref name="pmid19851811">{{cite journal| author=Grubbs EG, Callender GG, Xing Y, Perrier ND, Evans DB, Phan AT et al.| title=Recurrence of adrenal cortical carcinoma following resection: surgery alone can achieve results equal to surgery plus mitotane. | journal=Ann Surg Oncol | year= 2010 | volume= 17 | issue= 1 | pages= 263-70 | pmid=19851811 | doi=10.1245/s10434-009-0716-x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19851811  }}</ref>
* 16% of patients had positive margins after the [[surgery]].
|
* American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons recommended OA as the procedure of choice.<ref name="pmid19632968">{{cite journal| author=Zeiger MA, Thompson GB, Duh QY, Hamrahian AH, Angelos P, Elaraj D et al.| title=American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas: executive summary of recommendations. | journal=Endocr Pract | year= 2009 | volume= 15 | issue= 5 | pages= 450-3 | pmid=19632968 | doi=10.4158/EP.15.5.450 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19632968  }}</ref>
* The [[Peritoneal carcinomatosis|peritoneal spread]] is 60% with significant earlier recurrence.


Imaging should be done just before the surgery because ACC grow quickly and involvement of adjacent structures may change
* 30% of patients had positive margins.
* Recurrence rate of 86% in the OA group.
* Survival for patients with stage 2 was longer in those undergoing OA.
|}


Optimization of hormone excess in patients with functional masses especially those with Cushing’s syndrome
==== '''''Surgical approach''''' ====
1. [[Incision]] and [[exploration]] of the [[peritoneal cavity]].


Patients widespread distant metastatic disease in multiple organs or those with multiple metastatic deposits in one organ system unable to be completely resected should not undergo adrenalectomy.  
2. Evaluation of [[liver]] for [[metastasis]].


The primary tumor can instead be treated with external beam radiation for palliation along with other adjuncts to improve local symptoms and better control hormone excess,
3. Containment: a self-retaining retractor system with towels or [[laparotomy]] pads should be placed in such a way as to exclude the rest of the [[peritoneal cavity]] from the area of the [[tumor]] and other [[organs]] requiring [[resection]].


if present (247).
4. Mobilization of [[organs]] adjacent to [[tumor]].


Obstruction of the vena cava by tumor thrombus can lead to significant lower body edema, which leads to significant patient suffering. If tumor resection is not technically operable, vena cava stents can be placed, leading to temporary prevention of occlusion.  
5. En bloc [[resection]]. Preserve any [[Tissue (biology)|tissue]] overlying the [[tumor]].  


Debulking for control of hormone excess in the setting of known metastatic disease is also performed in some situations. The benefits of debulking must outweigh the risks of surgery in these patients who have poor wound healing and lengthy recovery periods due to preexisting debilitation
6. Regional [[lymphadenectomy]].


'''''1.  Surgical approach'''''
7. Provide intact en bloc specimen for [[Pathology|pathologic]] review.


'''''Adrenalectomy'''''
8. Mark field to facilitate [[postsurgical]] [[External beam radiotherapy|external beam radiation therapy]].


1. Incision and exploration of the peritoneal cavity.
9. Dictate operative report.


2. Evaluation of liver for metastasis
==== '''''Recurrence of ACC''''' ====
* The number of [[organs]] involved by [[tumor]] at the time of the first [[metastasis]] is a predictor of survival.<ref name="pmid23150691">{{cite journal| author=Erdogan I, Deutschbein T, Jurowich C, Kroiss M, Ronchi C, Quinkler M et al.| title=The role of surgery in the management of recurrent adrenocortical carcinoma. | journal=J Clin Endocrinol Metab | year= 2013 | volume= 98 | issue= 1 | pages= 181-91 | pmid=23150691 | doi=10.1210/jc.2012-2559 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23150691  }}</ref>
* University of Michigan data shows the site of first [[metastasis]] can also be used to predict  the survival.
* Recurrence in the [[peritoneum]] outside the [[tumor]] bed has the worst survival.
* [[Surgery]] is indicated in those [[patients]] with [[disease]] confined to one site or [[Organ (anatomy)|organ]].
* Waiting 3 months while treating with [[chemotherapy]] to assess for [[tumor]] responsiveness of progression. If progression is not rapid, [[surgery]] may proceed with greater benefit.<ref name="pmid23158185" />
* The [[median]] survival of 74 months in those undergoing complete second resections and a median survival of 16 months in those undergoing incomplete second resection.<ref name="pmid17062775">{{cite journal| author=Assié G, Antoni G, Tissier F, Caillou B, Abiven G, Gicquel C et al.| title=Prognostic parameters of metastatic adrenocortical carcinoma. | journal=J Clin Endocrinol Metab | year= 2007 | volume= 92 | issue= 1 | pages= 148-54 | pmid=17062775 | doi=10.1210/jc.2006-0706 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17062775  }}</ref>


3. Containment A self-retaining retractor system with towels or laparotomy pads should be placed in such a way as
== Video shows laparoscopic retroperitoneal adrenalectomy ==
 
{{#ev:youtube|aV2cL5z1lWo}}
to exclude the rest of the peritoneal cavity from the area of the tumor and other organs requiring
 
resection.4. Mobilization of organs
 
adjacent to tumor
 
5. En bloc resection. Preserve any tissue overlying the tumor.
 
6. Regional lymphadenectomy
 
7. Provide intact en bloc specimen for pathologic review
 
8. Mark field to facilitate postsurgical external beam radiation therapy
 
9. Dictate operative report
 
'''''2.  Lymph node dissection'''''
 
The role of lymph node sampling or formal regional
 
lymph node dissection in the treatment of ACC remains
 
unknown (248). the lymphadenectomy is performed based on following the arterial supply of adrenal tumors
 
Because lymph nodes ideally should be removed as part of
 
the en bloc resection, surgeons need to individually balance
 
the increased risk due to extended surgery (eg, bleeding)
 
with the presumed benefit of radical lymph node dissection.
 
regional lymph node dissection improved tumor
 
staging ability and led to a more favorable oncological
 
outcome in patients with otherwise localized ACC. (249)
 
'''''3. Open vs laparoscopic surgery'''''
 
LA has
 
become the gold standard for resection of benign adrenal
 
masses, and it has been shown to result in significantly
 
lower morbidity, less pain, shorter hospital stays, and decreased
 
overall time to recovery when compared with
 
open adrenalectomy (OA).
 
Application of laparoscopic instruments to the tumor
 
can result in shedding of malignant cells that is undetectable
 
to the operating surgeon.
 
Minimizing direct contact with the tumor
 
surface is important so as not to abrade cells from the
 
tumor surface or enter the tumor capsule.
 
Some surgeons compromise by initiating adrenalectomies
 
laparoscopically to assess for evidence of intraperitoneal
 
metastasis or invasion of the adrenal gland into
 
other organs (246, 251).
 
Published data comparing the efficacy of LA vs OA for
 
ACC are limited.
 
At least 7 studies have been published since 2010 that
 
specifically address the topic of LA vs OA for ACC.
 
Two studies published by the M.D. Anderson Cancer Center
 
reported a recurrence rate of 86% in the OA group (154
 
patients) and 100% in the LA group (6 patients) (251,
 
257). Recent recommendations
 
by the American Association of Clinical Endocrinologists
 
and the American Association of Endocrine
 
Surgeons advocate OA by an experienced surgeon as the
 
procedure of choice (254).  Conversely, the European Society
 
of Endocrine Surgeons and European Society for
 
Medical Oncology suggest LA could be performed for
 
stage 1 and 2 ACC tumors less than 8 or 10 cm if an R0
 
resection is performed and surrounding periadrenal tissue
 
removed (255, 256).
 
Local recurrence and peritoneal carcinomatosis was
 
more common in the LA group. In a study by Leboulleux
 
et al (258), peritoneal carcinomatosis occurred in only
 
25% of patients treated by OA, as opposed to 60% of
 
patients who underwent LA.
 
In contrast, other studies reported evidence that LA
 
may be comparable to OA in patients with stage 1 and 2
 
ACC based on no significant difference in recurrence-free
 
survival (259, 260).
 
Surgical studies should focus on local and peritoneal
 
recurrence as indicators of quality of surgical resection,
 
because type of operative approach likely has a much
 
smaller role in the development of distant metastases. A
 
retrospective study from the University of Michigan reviewed
 
88 ACC patients, 17 of whom underwent LA, and
 
79% of the operations were performed at outside facilities,
 
and no laparoscopic operations for ACC were performed
 
at the University of Michigan, potentially introducing
 
a referral bias (262). Although overall recurrence
 
rates were similar and despite on average smaller tumors
 
in the LA group (7.0 cm) compared with the OA group
 
(12.3 cm), the LA group had a significantly earlier recurrence
 
(9.2 vs 19.2 months). Furthermore, there were more
 
R1 or R2 resections or notation of intraoperative tumor
 
spill (50% vs 18%). These data suggest that although LA
 
may be technically feasible (even for large tumors) (263,
 
264), the use of LA in ACC leads to a shorter disease-free
 
interval and a higher incidence of incomplete resections.
 
These results were confirmed in an extended follow-up
 
study of 110 patients undergoing OA and 46 undergoing
 
LA. After LA,30%had positive margins or intraoperative
 
tumor spill compared with 16% of OA patients despite
 
larger tumors and more stage 3 tumors. Overall survival
 
for patients with stage 2 ACC was longer in those undergoing
 
OA, and time to visible tumor bed recurrence or
 
peritoneal recurrence in stage 2 patients was shorter in LA
 
patients.
 
In summary, existing data are inconclusive and more
 
studies are needed to better judge the equivalence of LA to
 
OA. In accordance with the experience gained at the authors’
 
institution, a conservative approach using an open
 
approach is recommended for all adrenocortical lesions
 
that cannot be classified as benign before surgery.
 
'''''4. Surgery for recurrent disease'''''
 
Extent of disease and tempo of disease progression
 
guide the decision for reoperation in the setting of recurrence.
 
The number of organs involved by tumor at the time
 
of the first metastasis is a predictor of survival (243, 265).
 
In addition, University of Michigan data show the site of
 
first metastasis can also be used to predict survival,
 
with those having tumor recurrence in the peritoneum outside
 
the tumor bed having the worst survival.
 
Surgery is indicated in those patients with disease confined to 1 site or organ.
 
Beyond that, decisions regarding resection must be individualized. The type of initial operative resection is important to the decision-making process for reoperation.
 
Patients with tumor bed recurrence who have undergone
 
LA are much more likely to have disease too small to be
 
detected by imaging elsewhere in the peritoneal cavity
 
compared with those having undergone OA based on our
 
experience.
 
median survival of 74 months (5-year survival, 57%) in those undergoing complete second resections vs a median survival of 16 months (5-year survival, 0%) in those undergoing incomplete second resection. tumor grade nor additional nonsurgical treatment
 
Tumor grade influences the decision for reoperation
 
because it correlates with survival (243, 245).
 
In those with low-grade tumors, tempo of disease progression can be slower and lead to longer survival with resection of sites of recurrence or metastasis.
 
those patients with high-grade tumors, other sites of disease often appear quickly.
 
wait 3 months while treating with chemotherapy to assess for tumor responsiveness and/or tempo of progression. If progression is not rapid, surgery may proceed with greater benefit, whereas those with evidence of


==References==
==References==
{{reflist|2}}
{{reflist|2}}
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Latest revision as of 12:31, 31 October 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Mohammed Abdelwahed M.D[3]

Overview

Surgery is the mainstay of treatment for adrenocortical carcinoma. Appropriate preoperative evaluation and operative planning are really important to assure the best outcome. Lymph nodes should be removed as part of the en bloc resection. Recurrence in the peritoneum outside the tumor bed has the worst survival. Surgery is indicated in those patients with disease confined to one site or organ.

Surgery

Laparoscopic adrenalectomy (LA) Open adrenalectomy (OA)
  • American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons recommended OA as the procedure of choice.[7]
  • The peritoneal spread is 60% with significant earlier recurrence.
  • 30% of patients had positive margins.
  • Recurrence rate of 86% in the OA group.
  • Survival for patients with stage 2 was longer in those undergoing OA.

Surgical approach

1. Incision and exploration of the peritoneal cavity.

2. Evaluation of liver for metastasis.

3. Containment: a self-retaining retractor system with towels or laparotomy pads should be placed in such a way as to exclude the rest of the peritoneal cavity from the area of the tumor and other organs requiring resection.

4. Mobilization of organs adjacent to tumor.

5. En bloc resection. Preserve any tissue overlying the tumor.

6. Regional lymphadenectomy.

7. Provide intact en bloc specimen for pathologic review.

8. Mark field to facilitate postsurgical external beam radiation therapy.

9. Dictate operative report.

Recurrence of ACC

  • The number of organs involved by tumor at the time of the first metastasis is a predictor of survival.[8]
  • University of Michigan data shows the site of first metastasis can also be used to predict the survival.
  • Recurrence in the peritoneum outside the tumor bed has the worst survival.
  • Surgery is indicated in those patients with disease confined to one site or organ.
  • Waiting 3 months while treating with chemotherapy to assess for tumor responsiveness of progression. If progression is not rapid, surgery may proceed with greater benefit.[4]
  • The median survival of 74 months in those undergoing complete second resections and a median survival of 16 months in those undergoing incomplete second resection.[9]

Video shows laparoscopic retroperitoneal adrenalectomy

{{#ev:youtube|aV2cL5z1lWo}}

References

  1. ↑ Sabolch A, Feng M, Griffith K, Hammer G, Doherty G, Ben-Josef E (2011). "Adjuvant and definitive radiotherapy for adrenocortical carcinoma". Int J Radiat Oncol Biol Phys. 80 (5): 1477–84. doi:10.1016/j.ijrobp.2010.04.030. PMID 20675074.
  2. ↑ Gaujoux S, Brennan MF (2012). "Recommendation for standardized surgical management of primary adrenocortical carcinoma". Surgery. 152 (1): 123–32. doi:10.1016/j.surg.2011.09.030. PMID 22306837.
  3. ↑ Reibetanz J, Jurowich C, Erdogan I, Nies C, Rayes N, Dralle H; et al. (2012). "Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma". Ann Surg. 255 (2): 363–9. doi:10.1097/SLA.0b013e3182367ac3. PMID 22143204.
  4. ↑ 4.0 4.1 Miller BS, Gauger PG, Hammer GD, Doherty GM (2012). "Resection of adrenocortical carcinoma is less complete and local recurrence occurs sooner and more often after laparoscopic adrenalectomy than after open adrenalectomy". Surgery. 152 (6): 1150–7. doi:10.1016/j.surg.2012.08.024. PMID 23158185.
  5. ↑ Gonzalez RJ, Shapiro S, Sarlis N, Vassilopoulou-Sellin R, Perrier ND, Evans DB; et al. (2005). "Laparoscopic resection of adrenal cortical carcinoma: a cautionary note". Surgery. 138 (6): 1078–85, discussion 1085-6. doi:10.1016/j.surg.2005.09.012. PMID 16360394.
  6. ↑ Grubbs EG, Callender GG, Xing Y, Perrier ND, Evans DB, Phan AT; et al. (2010). "Recurrence of adrenal cortical carcinoma following resection: surgery alone can achieve results equal to surgery plus mitotane". Ann Surg Oncol. 17 (1): 263–70. doi:10.1245/s10434-009-0716-x. PMID 19851811.
  7. ↑ Zeiger MA, Thompson GB, Duh QY, Hamrahian AH, Angelos P, Elaraj D; et al. (2009). "American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas: executive summary of recommendations". Endocr Pract. 15 (5): 450–3. doi:10.4158/EP.15.5.450. PMID 19632968.
  8. ↑ Erdogan I, Deutschbein T, Jurowich C, Kroiss M, Ronchi C, Quinkler M; et al. (2013). "The role of surgery in the management of recurrent adrenocortical carcinoma". J Clin Endocrinol Metab. 98 (1): 181–91. doi:10.1210/jc.2012-2559. PMID 23150691.
  9. ↑ Assié G, Antoni G, Tissier F, Caillou B, Abiven G, Gicquel C; et al. (2007). "Prognostic parameters of metastatic adrenocortical carcinoma". J Clin Endocrinol Metab. 92 (1): 148–54. doi:10.1210/jc.2006-0706. PMID 17062775.

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