Surgical cytoreduction and intraperitoneal chemotherapy for peritoneal carcinomatosis arising from the appendix.
ABSTRACT Peritoneal carcinomatosis (PC) originating in the appendix is a rare disease for which the long-term prognosis is poor. The aim of our study was to evaluate the results of an aggressive treatment approach used in our institution in the last decade.
We prospectively collected and analyzed data from all patients with PC. Treatment consisted of complete surgical cytoreduction of the tumour followed by intraperitoneal chemotherapy. Chemotherapy was either early postoperative intraperitoneal chemotherapy (EPIC) or hyperthermic intraperitoneal chemotherapy (HIPEC). We used Ronnett's classification for tumour grading (disseminated peritoneal adenomucinosis = grade 0, peritoneal mucinous carcinomatosis with intermediate features = grade 1 and peritoneal mucinous carcinomatosis = grade 2).
From September 1997 to June 2005, 37 patients underwent laparotomy with curative intent; 13 received EPIC and 11 HIPEC. Thirteen patients could not have complete cytoreductive surgery and received no intraperitoneal chemotherapy. The estimated 5-year overall survival was 56% (95% confidence interval [CI] 34%-77%) for all patients, 58% (95% CI 30%-86%) for patients who underwent EPIC and 60% (95% CI 10%-100%) for patients who underwent HIPEC (p = 0.97). Histologic grade was an important prognostic indicator as all patients with grade 0 tumours survived whereas no patients with grade 2 tumours survived (p < 0.001). Patients with grade 1 tumours had an estimated 87% (95% CI 64%-100%) 5-year overall survival. There was no mortality attributed to surgery. The overall complication rate was 36%, including fistulas (16%), intra-abdominal abscesses (12%) and hemorrhage (9%).
This therapeutic approach seems both feasible and safe in select patients. Patients with high-grade tumours are poor candidates for this treatment.
- [show abstract] [hide abstract]
ABSTRACT: A prominent part of treatment failure of gastrointestinal and gynecologic malignancy is dissemination to peritoneal surfaces. This has been associated with a limited survival and no reliable treatment strategies. A review of the natural history of carcinomatosis was performed and a rationale for intraperitoneal chemotherapy was sought. The pharmacology of chemotherapy administration into the peritoneal cavity was reviewed. The technology of perioperative intraperitoneal chemotherapy requires the administration of drugs along with moderate hyperthermia in the operating room as a planned part of the surgical procedure. The solution in which the chemotherapy is diluted has an effect upon the drug clearance from the peritoneal cavity. Also, the volume of the carrier solution affects the exposure of cancer nodules on peritoneal surfaces . New combinations of intraperitoneal chemotherapy administration when combined with optimal surgical technology for maximal chemotherapy effects should result in benefit to patients with peritoneal surface dissemination of gastrointestinal and gynecologic malignancy.Journal of Oncology Pharmacy Practice 10/2005; 11(3):111-9.
- [show abstract] [hide abstract]
ABSTRACT: Pseudomyxoma peritonei (PMP) is a clinical syndrome with a poorly defined natural history. Relative contributions of tumor biology, patient selection, and the extent of treatment on ultimate outcome are not well characterized. Patients treated at the Memorial Sloan-Kettering Cancer Center between 1980 and 2002 with a diagnosis of PMP were identified. Patient characteristics, pathologic features, and details of treatment were analyzed retrospectively. The 97 patients included in this study underwent a mean 2.2 +/- 0.1 operations (range, 1-6). Although complete cytoreduction was achieved in 55% (53/97), disease recurred in 91% (48/53) of patients. The median disease-free interval after complete cytoreduction was 24 months. The median overall survival was 9.8 years and was independently associated with low-grade pathologic subtype (P < 0.001) and the ability to achieve complete cytoreduction (P < 0.001). Ten-year survival was attained in 21% (20/97) of the patients, of which 90% (18/20) had low-grade pathologic features. At the time of death or completion of follow-up, only 12% (12/97) of the patients were disease free. Outcome in patients with PMP is strongly associated with tumor biology. Although improved survival is associated with low-grade pathology and tumors amenable to complete cytoreduction, recurrence of PMP is common. Treatment may be beneficial, particularly in controlling symptoms, but absolute cure, defined as a prolonged disease-free state, is uncommon.Annals of Surgery 02/2005; 241(2):300-8. · 6.33 Impact Factor
Article: Pseudomyxoma peritonei.[show abstract] [hide abstract]
ABSTRACT: Pseudomyxoma peritonei is a clinical entity that has lead to much confusion about its etiology, clinical manifestations, treatment, and prognosis. Pseudomyxoma peritonei is currently defined as a grade I mucinous adenocarcinoma that arises from a primary appendiceal adenoma. The clinical entity is defined by a redistribution phenomenon. This means that cancer cells from the appendix tumor are found localized at predetermined sites within the abdomen and pelvis but that the primary tumor may be small and inconspicuous. The small bowel is spared of mucinous tumor, while spaces beneath the hemidiaphragms and within the pelvis are filled by disease. The omentum is massively replaced by tumor in most patients. The disease, when treated by multiple surgical procedures, presents a median survival of approximately 2 years. Good results depend on early diagnosis and treatment before large volumes of disease and multiple surgical procedures lead to small bowel entrapment by tumor. In modern therapy using peritoneotomy procedures and intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil, the long-term survival at 10 years approaches 80 percent.Cancer treatment and research 02/1996; 81:105-19.
© 2009 Canadian Medical Association Can J Surg, Vol. 52, No. 2, April 2009
Accepted for publication
Nov. 20, 2007
Dr. L. Sideris
Division of General Surgical Oncology
Department of Surgery
5415 boul. de l’Assomption
Montréal QC H1T 2M4
fax 514 252-0896
RESEARCH • RECHERCHE
Surgical cytoreduction and intraperitoneal
chemotherapy for peritoneal carcinomatosis
arising from the appendix
Lucas Sideris, MD*
Andrew Mitchell, MD†
Pierre Drolet, MD‡
Guy Leblanc, MD*
Yves E. Leclerc, MD*
Pierre Dubé, MD, MSc*
From the Departments of *Surgery,
†Pathology and ‡Anesthesiology,
Maisonneuve-Rosemont Hospital, Uni-
versité de Montréal, Montréal, Que.
Background: Peritoneal carcinomatosis (PC) originating in the appendix is a rare
disease for which the long-term prognosis is poor. The aim of our study was to
evaluate the results of an aggressive treatment approach used in our institution in
the last decade.
Methods: We prospectively collected and analyzed data from all patients with PC.
Treatment consisted of complete surgical cytoreduction of the tumour followed by
intraperitoneal chemotherapy. Chemotherapy was either early postoperative intra-
peritoneal chemotherapy (EPIC) or hyperthermic intraperitoneal chemotherapy
(HIPEC). We used Ronnett’s classification for tumour grading (disseminated peri-
toneal adenomucinosis = grade 0, peritoneal mucinous carcinomatosis with intermedi-
ate features = grade 1 and peritoneal mucinous carcinomatosis = grade 2).
Results: From September 1997 to June 2005, 37 patients underwent laparotomy
with curative intent; 13 received EPIC and 11 HIPEC. Thirteen patients could not
have complete cytoreductive surgery and received no intraperitoneal chemotherapy.
The estimated 5-year overall survival was 56% (95% confidence interval [CI]
34%–77%) for all patients, 58% (95% CI 30%–86%) for patients who underwent
EPIC and 60% (95% CI 10%–100%) for patients who underwent HIPEC (p = 0.97).
Histologic grade was an important prognostic indicator as all patients with grade 0
tumours survived whereas no patients with grade 2 tumours survived (p < 0.001).
Patients with grade 1 tumours had an estimated 87% (95% CI 64%–100%) 5-year
overall survival. There was no mortality attributed to surgery. The overall compli-
cation rate was 36%, including fistulas (16%), intra-abdominal abscesses (12%) and
Conclusion: This therapeutic approach seems both feasible and safe in select pa-
tients. Patients with high-grade tumours are poor candidates for this treatment.
Contexte : La carcinomatose péritonéale émanant de l’appendice est une maladie
rare dont le pronostic à long terme est sombre. Le but de notre étude était d’évaluer
les résultats d’une approche thérapeutique radicale utilisée dans notre établissement
depuis une dizaine d’années.
Méthodes : Nous avons recueilli et analysé de manière rétrospective les données
concernant tous les patients atteints de carcinomatose péritonéale appendiculaire. Le
traitement reposait sur une cytoréduction chirurgicale complète de la tumeur, suivie
d’une chimiothérapie intrapéritonéale. La chimiothérapie était administrée sous
forme de chimiothérapie intrapéritonéale postopératoire immédiate (CIPPI) ou de
chimiohyperthermie intrapéritonéale (CHIP). Nous avons stadifié les tumeurs selon
la classification de Ronnett (adénomucinose péritonéale diffuse = grade 0, carcino-
matose péritonéale mucineuse associée à des caractéristiques intermédiaires = grade 1
et carcinomatose péritonéale mucineuse = grade 2).
Résultats : Entre septembre 1997 et juin 2005, 37 patients ont subi une laparo-
tomie à visée curative; 13 ont reçu la CIPPI et 11, la CHIP. Treize patients n’ont
pas pu subir de chirurgie cytoréductrice complète et n’ont pas reçu de chimio-
thérapie intrapéritonéale. La survie globale estimée à 5 ans a été de 56 % (inter-
valle de confiance [IC] à 95 %, 34% à 77 %) pour tous les patients, de 58 % (IC à
95 %, 30% à 86 %) pour les patients qui ont reçu la CIPPI et de 60 % (IC à 95 %,
10% à 100 %) pour les patients qui ont reçu la CHIP (p = 0,97). Le stade his-
tologique a servi d’important indicateur pronostique puisque tous les patients
présentant des tumeurs de grade 0 ont survécu, tandis qu’aucun des patients qui
présentaient des tumeurs de grade 2 n’a survécu (p < 0,001). Les patients qui
avaient des tumeurs de grade 1 ont présenté une survie globale estimée à 5 ans de
been published proposing a novel aggressive treatment
approach with curative intent.2,5–12This approach consists of
treating macroscopic PC with complete cytoreductive
surgery and treating residual microscopic PC with immedi-
ate intraperitoneal chemotherapy. Complete cytoreductive
surgery is necessary because experimental studies show that
drug penetration is limited to a few cell layers under the sur-
face of the tumour.13,14Intraperitoneal chemotherapy must
be immediate to avoid trapping residual tumour cells in the
postoperative fibrin adhesions.15Immediate intraperitoneal
chemotherapy can be delivered in 2 ways: as early postoper-
ative intraperitoneal chemotherapy (EPIC), which is admin-
istered in normothermia, or as hyperthermic intraperitoneal
chemotherapy (HIPEC), which is delivered intraoperatively
along with a heating system. The latter method leads to high
local concentration of antineoplastic agents;16–19with in-
creased cytotoxicity due to the hyperthermia,18,20the cytotox-
icity of oxaliplatin is increased by 180%.21
Results of this treatment approach for PC originating in
the appendix have been encouraging, with overall 5-year
survival ranging from 40% to 87% and 10-year survival
ranging from 21% to 85%.1,2,8,22–29The aim of our study was
to evaluate an aggressive treatment approach combining
cytoreductive surgery and intraperitoneal chemotherapy
used in our institution over the last decade.
eritoneal carcinomatosis (PC) originating in the ap-
pendix is an uncommon disease, with poor long-term
prognosis.1–6In recent years, a number of studies have
From a prospective database we included all patients with
peritoneal surface spread of appendiceal cancer treated in our
tertiary care centre between January 1998 and December
2005. Both our institution’s clinical trial review board and
an independent ethics committee approved our study.
All patients were offered treatment consisting of maximal
surgical cytoreduction with immediate intraperitoneal
chemotherapy if they fulfilled the following criteria: diagno-
sis proven by histological examination, no evidence of vis-
ceral metastasis on computed tomography (CT) scans of the
chest and abdomen, technically resectable disease and gen-
eral health status good enough to tolerate major surgery.
We collected and analyzed the following factors: demo-
graphic data, surgical procedures performed, pathologic
diagnoses, complications and length of stay in hospital.
Surgery for peritoneal carcinomatosis
For this series, we defined maximal cytoreductive surgery as
resection of all tumour deposits greater than 2 mm in diam-
eter. This condition was mandatory before administering
immediate intraperitoneal chemotherapy because this treat-
ment is efficient only for nodules smaller than 2 mm.18,19
We approached the abdomen through a xyphopubic
midline incision. After complete adhesiolysis, we con-
firmed the diagnosis of PC by frozen section and scored
the extent of PC according to Sugarbaker’s peritoneal
index.30,31This index takes into account the number of
invaded areas among a total of 13, and the maximal size
of tumour nodules within 3 possible groups (< 5 mm,
5 mm to 5 cm, > 5 cm). When PC seemed resectable, we
removed the primary tumour and all visceral or peri-
toneal surface tumour deposits as completely as possible
by using peritonectomy procedures, as described by
Sugarbaker.32Macroscopically detectable disease had to
be completely resected before administering intraperi-
toneal chemotherapy. However, the presence of remain-
ing tumour seeding smaller than 2 mm in diameter was
allowed if it was located on the small bowel or stomach.
Depending on the extent of disease, complete cytoreduct-
ive surgery may have required several hours to perform.
If, after thorough exploration, we considered the PC re-
section to be incomplete, no immediate intraperitoneal
chemotherapy was administered and patients received
Immediate intraperitoneal chemotherapy
We performed immediate intraperitoneal chemotherapy
to allow for optimal exposure to the chemotherapy solu-
tion before any adhesions formed that might impair the
distribution of the drug. Patients underwent either EPIC
(1998–2002) or HIPEC (2002–2005). The EPIC proced-
ure consisted of administering normothermic intraperi-
toneal chemotherapy for 5 days in the immediate postop-
erative period. We installed 3 drains (Tenkhoff catheters)
for intraperitoneal drug instillation. We administered
mitomycin C (10 mg/m2) on day 1 and 5-fluorouracil
(15 mg/kg) on days 2–5, given in a 2-L solution 23h/d, ac-
cording to the procedure described by Sugarbaker.30,31The
intra-abdominal contents were thus soaked in the
chemotherapy solution for 5 days, and we unclamped the
drains thereafter to allow for complete evacuation of the
J can chir, Vol. 52, No2, avril 2009
87 % (IC à 95 %, 64% à 100 %). Aucun décès n’a été attribué à la chirurgie. Le
taux global de complications a été de 36 %, incluant des fistules (16 %), des abcès
intra-abdominaux (12 %) et des hémorragies (9 %).
Conclusion : Cette approche thérapeutique semble faisable et sécuritaire chez cer-
tains patients. Les patients porteurs de tumeurs de haut grade sont avancées sont de
mauvais candidats pour ce type de traitement.
The HIPEC procedure consisted of the delivery of
intraperitoneal chemotherapy intraoperatively along with a
heating system. We used oxaliplatin in all but 1 patient
(this patient received mitomycin C) because of its efficacy
against colorectal cancer, and because it is much shorter to
administer than mitomycin C, according to a phase I
study.18We performed HIPEC with a continuous closed
circuit using 4 36-French drains (2 inlets and 2 outlets)
connected to 2 pumps. We used 1 heating unit and 2 heat
exchangers to eliminate a Y connector that could reduce
flow rates and heat homogeneity.19The procedure took
place with the abdomen open and the skin sutured to a
retractor ring placed above the anterior surface of the
abdomen. The flow rate was 1 L/min for each pump. Four
thermal probes inside the peritoneal cavity provided con-
tinuous temperature feedback, and the intra-abdominal
temperature was maintained everywhere between 42°C
and 43°C. The duration of perfusion was 30 minutes from
the time when optimal temperature (42–44°C) was
reached. Usually, less than 5 minutes were necessary to
reach a high homogeneous temperature, leading to a total
peritoneal infusion duration of about 35 minutes. After-
wards, the infusion liquid was completely evacuated. The
total oxaliplatin dose was delivered as a bolus mixed with
5% dextrose at the beginning of the procedure. The total
amount of peritoneal fluid used was based, as for oxali-
platin dosage, on body surface area: 2 L/m2. Dosage of ox-
aliplatin was 460 mg/m2, as recommended in a previous
study in humans.18Instillation volume and oxaliplatin
dosage both resulted in a similar intraperitoneal concentra-
tion of the drug in each patient.
An experienced pathologist (A.M.) performed the patho-
logic classification. When surgery of the primary tumour
was performed in an institution other than ours, the
pathology material was sent to us for revision. We per-
formed the tumour grading of both primary (when avail-
able) and peritoneal deposits according to Ronnett’s
histologic classification.33We considered disseminated
peritoneal adenomucinosis to be a grade 0 tumour; the
tumour was characterized histologically by the presence of
scant low-grade adenomatous mucinous epithelium within
abundant extracellular mucin and associated fibrosis. We
classified peritoneal mucinous carcinomatosis as a grade 2
tumour; this tumour had the cytologic and architectural
features of higher-grade mucinous carcinoma associated
with extracellular mucin, often with invasive components
and sometimes demonstrated signet ring cell differentia-
tion. A grade 1 tumour consisted of peritoneal mucinous
carcinomatosis with intermediate features combining
grade 0 and grade 2 characteristics; such tumours were
derived from well-differentiated mucinous adenocarcin-
omas of the appendix.
We administered systemic chemotherapy preoperatively
for 3–6 months among patients with extensive disease.
The aim of this systemic treatment was to diminish the
tumour burden and maximize the chances of complete
surgical cytoreduction thereafter. We administered adju-
vant systemic chemotherapy only among patients who had
grade 2 disease for 6 months. Chemotherapy consisted of
5-fluorouracil in addition to irinotecan or oxaliplatin once
these drugs became available. In our institution, systemic
chemotherapy for digestive tumours is administered by
We saw patients at the outpatient clinic in 3- to 4-month
intervals, and we performed a physical examination. We
obtained a CT scan of the abdomen and pelvis every
6 months for 5 years, and yearly thereafter.
We prospectively collected all data. No patient was lost
during follow-up. We established survival curves using the
Kaplan–Meier method, and we compared the results using
the log-rank test. We considered the differences to be sig-
nificant at p ≤ 0.05.
From September 1997 to June 2005, 37 patients with a
PC originating in the appendix underwent laparotomy
Can J Surg, Vol. 52, No. 2, April 2009
2 had repeat
3 with no
Fig. 1. Patient distribution. EPIC = early postoperative intraperi-
toneal chemotherapy; HIPEC = hyperthermic intraperitoneal
with curative intent. There were 17 men and 20 women,
with a mean age of 51 (33–73) years. The primary tumour
had been removed in 20 patients. At laparotomy, 12 pa-
tients had nonresectable disease, either because the PC
was too extensive or because of intraoperative discovery of
visceral metastasis (Fig. 1). Two of these patients under-
went repeat surgery with successful cytoreduction and in-
traperitoneal chemotherapy after 6 months of systemic
chemotherapy. Three other patients who received initial
diagnoses of a mucinous tumour of the appendix with lim-
ited peritoneal disease had no evidence of PC when we
performed a second-look laparotomy in our centre
6 months later. These patients had undergone appendec-
tomy along with the complete removal of peritoneal tu-
mours at another centre before being referred to us.
Hence, these patients did not receive intraperitoneal
We performed complete surgical cytoreduction fol-
lowed by immediate intraperitoneal chemotherapy in
24 patients: 13 EPIC and 11 HIPEC. Twelve of these
patients with extensive peritoneal disease underwent pre-
operative systemic chemotherapy (including the 2 patients
who had repeat surgery). Details of the surgical parameters
are outlined in Table 1. There was no mortality attributed
to surgery. The overall complication rate was 36%, includ-
ing fistulas (16%), intra-abdominal abscesses (12%) and
hemorrhage (9%). One patient in the HIPEC group expe-
rienced grade 2 neuropathy that lasted for 1 week after
surgery. That same patient also experienced grade 3
thrombocytopenia 1 week postoperatively. There was no
statistically significant difference in the complication rates
between the EPIC and HIPEC groups.
Final pathology reports showed diffuse peritoneal ade-
nomucinosis (grade 0) in 5 patients (21%; EPIC n = 2,
HIPEC n = 3), an intermediate type (grade 1) in 12 pa-
tients (50%; EPIC n = 7, HIPEC n = 5) and peritoneal mu-
cinous carcinomatosis (grade 2) in 7 patients (29%; EPIC
n = 4, HIPEC n = 3).
We administered systemic adjuvant chemotherapy in
the 7 patients with grade 2 tumours. Treatments started
within 6–10 weeks after surgery, depending on the pa-
Median follow-up was 23 (range 7–81) months for the
entire series. The estimated 5-year overall survival rate for
the entire series was 56% (95% confidence interval [CI]
34%–77%) and 59% (95% CI 29%–88%) for patients
who underwent immediate intraperitoneal chemotherapy
(Fig. 2). The estimated 5-year overall survival for patients
who underwent EPIC was 58% (95% CI 30%–86%), and
60% (95% CI 10%–100%) for patients who underwent
HIPEC (Fig. 3). There was no statistically significant dif-
ference between these groups with regards to survival. At
the time of data analysis, 5 patients had isolated peritoneal
recurrence, 4 patients had visceral recurrence only and
1 patient had both.
J can chir, Vol. 52, No2, avril 2009
Table 1. Intraoperative data for 24 patients who received
complete cytoreductive surgery followed by immediate
Parameter Mean SD Median Range
No. of organ
No. of anastomoses
Duration of surgery, min
Blood loss, mL
Length of stay, d
SD = standard deviation.
*This index can range from 1 to 39. The 13 areas of the abdominal cavity are scored as
follows: 0 when there is no tumour deposit, 1 when tumour deposit is sized between 0
and 5 mm, 2 when tumour deposit is sized between 5 mm and 5 cm, and 3 when
tumour deposit is sized greater than 5 cm or diffuse.
7 3 0
1 4 6 0
2 1 9 0
2 9 2 0
p = 0.97
No. years post-treatment
Overall survival, n = 37
Survival after IIPC, n = 24
Fig. 2. Overall survival for the entire series (intent-to-treat) and
for all patients who underwent complete surgical cytoreduction
followed by immediate intraperitoneal chemotherapy. IIPC = im-
mediate intraperitoneal chemotherapy.
2 9 2 0
p = 0.61
No. years post-treatment
Fig. 3. Overall survival results: early postoperative intraperi-
toneal chemotherapy (EPIC) versus intraperitoneal chemohyper-
Histologic grade was an important prognostic indicator
since all patients with grade 0 tumours survived, whereas
no patients with grade 2 tumours survived (p < 0.001). Pa-
tients with grade 1 tumours had an estimated 87% (95%
CI 64%–100%) 5-year overall survival (Fig. 4). Other
parameters such as age, sex, peritoneal index, duration of
surgery, blood loss and systemic chemotherapy (neoadju-
vant or adjuvant) had no statistically significant influence
Finally, we also followed the 3 patients who underwent
second-look laparotomy and who we found had no disease.
The first patient had a grade 0 tumour and was disease-free
after 20.6 months. The second had a grade 1 tumour
and was disease-free after 13.2 months. The third patient
had a grade 2 tumour and received 6 months of adjuvant
irinotecan-based systemic chemotherapy after her primary
surgery. She was disease-free after 8.6 months.
We started treating PC patients with intraperitoneal
chemotherapy more than 7 years ago. Nearly 60% of
these patients are still alive today. This is comparable with
most large series.2,4–6,9,10,12,34–38This treatment approach is
complex, and there is a high risk of complications in the
postoperative period. Hence, a multidisciplinary approach
by an experienced team is mandatory.
Our study confirmed the correlation between low histo-
logic grade and better prognosis demonstrated in previous
studies.1,39–41Similarly, high peritoneal index has been
shown to be an adverse prognostic factor in a series study-
ing colorectal PC.26In the presence of high-grade tumours,
the procedure is not curative, especially when the peri-
toneal index is high. All patients in our series with high-
grade tumours had a poor outcome (0% survival after
2 years). Conversely, an aggressive approach is warranted
when the histopathologic grade is low or very low, even
with a high peritoneal index (87% survival at 5 years). Very
low-grade disease may represent truly benign disease.5,42
As the surgery is often long, with large fluid shifts and a
high risk of postoperative complications, patients in our
series had to be relatively young and fit to be considered
for the procedure. This is an important factor reflected in
the absence of procedure-related deaths. Regarding mor-
bidity, 1 of 3 patients had significant complications after
the procedure. Most were infectious (fistulas and ab-
scesses). Intraperitoneal chemotherapy is probably largely
responsible for these complications.27,38,43,44In spite of its po-
tential deleterious effect on tissue, we did not observe any
increase in the complication rate when heat was combined
with intraperitoneal chemotherapy. The shorter exposition
of viscera to the chemotherapy solution (30 min v. 5 d)
may explain this phenomenon.
In our series, HIPEC did not seem more effective than
EPIC when used in the treatment of appendiceal PC, but
it is impossible to draw any conclusion since the number of
patients in each group was too small and there was no ran-
domization. At the beginning of our study, we used EPIC,
but when HIPEC became available in 2002 in our institu-
tion, we favoured this approach because there was evidence
in the literature of increased chemotherapy cytotoxicity
when using hyperthermia.18,20Furthermore, HIPEC is
more comfortable for the patient and is simpler for the
nursing staff. Despite no demonstrable survival advantage,
these reasons were deemed reasonable to justify the use of
Patients with a high peritoneal index can be helped by
preoperative (neoadjuvant) systemic chemotherapy, even if
the histologic grade is low. In our study, 10 patients who
received the complete treatment of surgery and immediate
intraperitoneal chemotherapy had been treated with
neoadjuvant chemotherapy before surgery. Two other pa-
tients considered to be initially nonresectable at first la-
parotomy became potentially curable after neoadjuvant
systemic treatment. The increasing availability of irinote-
can and oxaliplatin has come to offer some hope for these
classically refractory tumours. Furthermore, neoadjuvant
treatment may allow for improved patient selection.
During HIPEC, we chose oxaliplatin for its high effi-
cacy against colorectal cancer.45–50Before using this drug in
humans, we performed pharmacokinetics studies of oxali-
platin administered in pigs by intraperitoneal route at dif-
ferent temperatures. We found it possible to achieve very
high intracellular concentrations of oxaliplatin (potential-
ized by heat) without substantial systemic absorption, mak-
ing this technique relatively safe. Based on Elias’ stud-
ies16,18,26and ours, we considered it to be the drug of choice
for this disease.
We cannot measure precisely the effect of selecting a
particular treatment on the prognosis of patients with dif-
fuse peritoneal adenomucinosis. This would require a ran-
domized trial that would offer complete surgical cytore-
duction followed or not by immediate intraperitoneal
chemotherapy. Of note, Miner and colleagues51recently
Can J Surg, Vol. 52, No. 2, April 2009
2 9 2 0
No. years post-treatment
p ≤ 0.001
Fig. 4. Overall survival according to histologic grade.
reported on the long-term survival of patients who re-
ceived treatment for pseudomyxoma peritonei by repeat
surgical cytoreduction without intraperitoneal chemother-
apy, with a median survival of 9.8 years; 21% of patients
with low-grade disease survived 10 years.
Finally, for patients with no residual disease at second-
look laparotomy 6 months after complete surgical excision
of the appendix and PC, our experience showed that they
were all disease-free after several months. However, longer
follow-up is needed to determine whether prophylactic
intraperitoneal chemotherapy is needed when no disease is
found at second-look laparotomy, especially for patients
with higher-grade tumours.
Although the results of this study are preliminary, the
treatment of peritoneal carcinomatosis arising from the ap-
pendix by complete surgical cytoreduction followed by im-
mediate intraperitoneal chemotherapy seems both feasible
and safe in select patients. However, patients with
high-grade tumours are poor candidates for this treatment.
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tonei of appendiceal origin: a clinicopathologic analysis of 101 pa-
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2. van Ruth S, Acherman YI, van de Vijver MJ, et al. Pseudomyxoma
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