LETTER TO THE EDITOR

In Reply: PseudomyxomaPeritonei: Debulk orMaximal Cytoreduction?

TO THE EDITORS:

Thank you for asking us to respond to Dr. Pocard and

colleagues’ comments on the adoption of a two-step proce-

dure for pseudomyxoma peritonei. This was made in

response to our study published in the Annals of Surgical

Oncology.1 Our study critically evaluated the perioperative

outcomes of 145 patients with pseudomyxoma peritonei who

were treated with cytoreductive surgery and perioperative

intraperitoneal chemotherapy. Many patients presented with

advanced disease (mean PCI = 20) and underwent a lengthy

surgical procedure (mean duration = 10 h). The mortality

rate in this group of patients was 3%, and the grade III/IV

morbidity rate was 45%. Two independent predictors of a

poor perioperative outcome were identified: ASA score C 3

and operation length C 10 h. As stated by Pocard and col-

leagues, these data are concordant with French data as well as

other centers offering this treatment modality. In the French

multicentric study conducted by the Association Francaise

de Chirurgie of 301 patients with pseudomyxoma peritonei

undergoing cytoreductive surgery and intraperitoneal che-

motherapy, Elias et al. reported a mortality rate of 4.4% and

severe morbidity rate of 40%.2

In light of the strong association between ASA status

and duration of operation with poor perioperative outcome,

Pocard and colleagues have suggested that because ASA

status may not be reduced other than by altering nutritional

status, a rather novel strategy to reduce operation length to

improve perioperative outcome should be adopted. This

strategy adopts the principles of ‘‘damage control surgery,’’

which is restricted to emergency cases. Firstly, we are

pleased to report that in patients who are manifesting

symptoms of a bowel obstruction secondary to peritoneal

carcinomatosis, we do electively admit these patients for

in-hospital total parenteral nutrition feeding preoperatively

to manage bowel obstruction. Secondly, damage control

surgery, a principle of trauma surgery, when applied for

abdominal trauma is performed by surgical repair of major

visceral tears followed by intensive unit care. Once the

patient is stable, a second operation is then undertaken to

repair any remaining smaller tears. The advantage of this

approach serves to provide a second-look operation,

allowing a more extensive surgery to be undertaken when

the patient is more stable for which there is less likelihood

of an adverse outcome. There is no evidence to support the

efficacy of this approach in abdominal trauma as reported in

a Cochrane review.3 In the context of a malignant disease

such as pseudomyxoma peritonei, we have not adopted the

strategy of performing debulking surgical procedures such

as omentectomy, subtotal colonic resection, and ileocolonic

anastomosis or ileostomy unless the patient is not fit for a

surgical cytoreduction. It has been reported that two-stage

procedures may result in disease progression that make it

impossible to perform a complete cytoreduction.4 Debul-

king surgery and the associated negative outcomes in

pseudomyxoma peritonei is well established for the fol-

lowing reasons: alteration of the surgical planes for a

complete peritonectomy, adhesions that develop require

additional time for adhesiolysis in the second operation and

form a bed for tumor cell entrapment, incomplete cytore-

duction has been well regarded as a negative prognostic

factor for survival, and harboring residual disease is a risk

factor for developing malignant transformation of the

mucinous neoplasm from low to high grade.5 For these

reasons, we have advocated that general surgeons who

encounter an unexpected appendiceal malignancy at the

time of appendectomy should at most perform an appen-

dectomy, partial caecetomy, or right hemicolectomy

without undertaking any tumor debulking surgery to limit

the amount of surgical dissection performed. Murphy et al.

from the Basingstoke peritonectomy unit have proposed an

algorithm for which large appendiceal tumors [2 cm

should be treated by right hemicolectomy.6 If the tumor is

\2 cm, and the base of the appendix and mesoappendix is

clear, only appendectomy should be performed. If there is

evidence of mucinous ascites, appendectomy or, if not

possible, tissue biopsy alone should be sufficient prior to

referral to a specialist center for diagnostic workup. We

believe this management algorithm is appropriate. The

majority of the patients we treat have undergone tumor

debulking surgery, which may explain the morbid results.

However, in recent years, surgeons have became aware of

the biology of this unique disease for which a favorable

outcome may be achieved through cytoreductive surgery

and hyperthermic intraperitoneal chemotherapy; prudent

recognition of the manifestation of this disease by surgeons

in our country has led to early referral of patients. From our

peritonectomy database, we have undertaken retrospective

Ann Surg Oncol (2011) 18:284–285

DOI 10.1245/s10434-010-1194-x

chart reviews to compare upfront cytoreduction compared

with delayed cytoreduction and to study the critical time

points of pseudomyxoma peritonei surgery. These manu-

scripts are being prepared for publication.

We appreciate the Hippocratic Oath, Primum non n

ocere (First, do no harm), and the strategy propose by

Dr. Pocard. Clearly a randomized trial of tumor debulking

versus complete cytoreductive surgery and hyperthermic

intraperitoneal chemotherapy according to an intention to

treat analysis to evaluate progression-free survival would

be an attractive study. However, the knowledge of the poor

outcome from debulking surgery makes it difficult for a

peritonectomy surgeon to commit to such a randomization.

At the current time, our experience has informed us that the

best possible outcome for patients with pseudomyxoma

peritonei is to undergo a complete cytoreduction and

hyperthermic intraperitoneal chemotherapy to achieve the

longest possible survival that is achievable despite under-

going an operation with a significant risk of developing a

severe postoperative complication compared with suffering

the consequence of ongoing subacute bowel obstruction

and ascites from the manifestations of peritoneal carcino-

matosis and its debilitating symptoms. Further, this

treatment is no longer regarded as experimental therapy.

Akshat Saxena, BMedSc, Terence C. Chua, BSc (Med)

(Hons), MBBS, and David L. Morris, MD, PhD

Department of Surgery, Hepatobiliary and Surgical

Oncology Unit, University of New South Wales, St George

Hospital, Sydney, Australia

e-mail: a.saxena@ugrad.unimelb.edu.au

Published Online: 7 July 2010

� Society of Surgical Oncology 2010

REFERENCES

1. Saxena A, Yan TD, Chua TC, Morris DL. Critical assessment of

risk factors for complications after cytoreductive surgery and

perioperative intraperitoneal chemotherapy for pseudomyxoma

peritonei. Ann Surg Oncol. 2010;17:1291–301.

2. Elias D, Gilly F, Quenet F, Bereder JM, Sideris L, Mansvelt B,

et al. Pseudomyxoma peritonei: A French multicentric study of

301 patients treated with cytoreductive surgery and intraperitoneal

chemotherapy. Eur J Surg Oncol. 2010;36:456–62.

3. Cirocchi R, Abraha I, Montedori A, Farinella E, Bonacini I,

Tagliabue L, et al. Damage control surgery for abdominal trauma.

Cochrane Database Syst Rev. 2010;1 (CD007438).

4. De Simone M, Scuderi S, Vaira M, Costamagna D, Barone R,

Fiorentini G, et al. Treatment of pseudomyxoma peritonei with

two times—cytoreduction and hyperthermic antiblastic peritoneal

perfusion (HAPP). J Exp Clin Cancer Res. 2003;22:25–8.

5. Jarvinen P, Jarvinen HJ, Lepisto A. Survival of patients with

pseudomyxoma peritonei treated by serial debulking. ColorectalDis. 2009. doi:10.1111/j.1463-1318.2009.01947.x.

6. Murphy EMA, Farquharson SM, Moran BJ. Management of an

unexpected appendiceal neoplasm. Br J Surg. 2006;93:783–92.

Pseudomyxoma Peritonei: Debulk or Maximal Cytoreduction? 285