Peritonectomy for Peritoneal Carcinomatosis: Long-TermOutcomes from a Single Brazilian Institution

Eduardo Akaishi Æ Frederico Teixeira Æ Marcelo Katayama ÆNelson Mizumoto Æ Frederico P. Costa Æ Antonio Carlos Buzaid ÆPaulo M. Hoff

Published online: 24 January 2009

� Societe Internationale de Chirurgie 2009

Abstract

Background The objective of this study was to evaluate

the long-term outcomes of a single institution, Hospital

Sırio-Libanes in Sao Paulo, Brazil, regarding the treatment

of peritoneal carcinomatosis.

Methods Between October 2002 and October 2006, 46

consecutive patients were treated with radical cytoreduction

and hyperthermic peritoneal chemotherapy. There were 21

patients with peritoneal surface malignancy (PSM) from

colorectal origin (among whom 8 had an appendiceal pri-

mary), 15 with ovarian carcinomas, 2 with primary peritoneal

mesotheliomas, and 8 with other cancers. The median age was

49 years (range 18–77 years). All patients were followed for a

median of 20 months. Demographic data, tumor histology,

the peritoneal carcinomatosis index (PCI), operative proce-

dures (extension of resection, lymphadenectomy), and

hyperthermic intraperitoneal chemotherapy (HIPEC)

characteristics (drugs, temperature, duration) were prospec-

tively recorded. Perioperative mortality and morbidity and the

long-term outcome were assessed.

Results Complete cytoreduction was achieved in 45

patients. The median PCI was 11, and the mean operating

time was 17 h. There were no procedure-related deaths, but

major morbidity was observed in 52% and included fistu-

las, abscesses, and hematologic complications. The overall

Kaplan–Meier 4-year estimated survival was 56%. Among

patients with PSM from colorectal carcinoma, the esti-

mated 3-year survival was 70%. Nine (42%) patients had a

recurrence, three with peritoneal disease. The median dis-

ease-free-interval was 16 months. The ovarian cancer

patients had an estimated 4-year survival rate of 75% and

median disease-free survival duration of 21 months.

Conclusions Cytoreductive surgery with HIPEC may

improve survival of selected patients with peritoneal car-

cinomatosis, with acceptable morbidity.

Introduction

Malignancies that involve the abdominal and pelvic cavi-

ties commonly cause their greatest morbidity and mortality

through progressive involvement of the peritoneal surfaces

in a process commonly referred to as peritoneal carcino-

matosis. This process is often seen in patients suffering

from appendiceal, ovarian, colorectal, or gastric cancer,

mesothelioma, or pseudomyxoma peritonei. Peritoneal

carcinomatosis is a fatal disease when treated with

conventional surgical and medical interventions. The use of

a multidisciplinary approach, combining an extensive

surgical intervention with hyperthermic intraoperative

intraperitoneal chemotherapy (HIPEC), offers the best

E. Akaishi (&) � F. Teixeira � M. Katayama

Department of Surgical Oncology, Sao Paulo University School

of Medicine (LIM62); Centro de Oncologia, Hospital Sirio

Libanes, Rua Dona Adma Jafet, 91, CEP 01308-050 Sao Paulo,

SP, Brazil

e-mail: eduardoakaishi@uol.com.br

Present Address:E. Akaishi

Rua Sao Firmo 100, Sao Paulo, Brazil

N. Mizumoto

Department of Anesthesiology, Sao Paulo University School of

Medicine (LIM62); Centro de Oncologia, Hospital Sirio

Libanes, Sao Paulo, Brazil

F. P. Costa � A. C. Buzaid � P. M. Hoff

Department of Medical Oncology, Sao Paulo University School

of Medicine (LIM62); Centro de Oncologia, Hospital Sirio

Libanes, Sao Paulo, Brazil

123

World J Surg (2009) 33:835–839

DOI 10.1007/s00268-008-9880-6

hope for long-term control and possibly cure of this drea-

ded disease.

Peritonectomy provides the most reliable surgical tech-

nique to reduce the volume of low- or high-grade tumors to

the lowest possible level [1–3]. In addition, the pharma-

cologic basis for intraperitoneal chemotherapy

administration has been well established [4–6], and prior

clinical studies have shown that patients with peritoneal

carcinomatosis derived from cancer of the colon or

appendix can be effectively treated by this approach, with

reported long-term disease-free survivors [7, 8].

The size of the residual tumor after surgery is of major

importance because chemotherapy does not reliably pene-

trate tumor nodules that are [5 mm in diameter [4].

Intraoperative administration of heated intraperitoneal

chemotherapy has been designed to overcome such obsta-

cles. Hyperthermia is added for its potential direct

cytotoxic effect as well as the perceived synergism against

tumor cells when it is combined with chemotherapy [9].

The purpose of this review was to analyze the morbidity,

mortality, and long-term outcomes associated with this

type of treatment when given to patients with peritoneal

carcinomatosis in a single institution in Brazil.

Patients and methods

A systematic review of our records showed that 46 patients

were treated with peritonectomy and HIPEC between

October 2002 and October 2006. Although these patients

had not been included in a prospective trial, there were a

number of selection factors that influenced the composition

of this patient population. Exclusion criteria included

advanced age; Eastern Cooperative Oncology Group

(ECOG) performance status [2; abnormal cardiac, hepatic,

or renal function; clear evidence of massive abdominal

cavity involvement on clinical or imaging examination;

and/or the presence of extraabdominal metastasis.

The characteristics of the 46 selected patients are shown

in Table 1. There were 31 women and 15 men with a

median age of 49 years (range 18–77 years). Primary

tumors included 13 colorectal, 8 appendiceal, and 15

ovarian cancers; 2 primary peritoneal mesotheliomas; and

8 other cancers (including 1 benign cystic mesothelioma, 2

cases of sarcomatosis, 1 fibrolamellar hepatocarcinoma, 1

cortical adrenal carcinoma, 1 neuroendocrine gastric car-

cinoma, 1 gastric adenocarcinoma, and 1 pancreatic

cancer).

Surgery

The technique for cytoreductive surgery has been previ-

ously described [10]. In brief, cytoreductive surgery

comprises a combination of visceral and parietal periton-

ectomy procedures: omentectomy, splenectomy, left

subdiaphragmatic peritonectomy, right subdiaphragmatic

peritonectomy, pelvic peritonectomy, sigmoidectomy,

cholecystectomy, and lesser omentectomy. High-voltage,

ball-tip electrode electrosurgery was used not only to per-

form the peritonectomy but also to remove tumor nodules

from the surface of the small bowel and small bowel

mesentery [11]. Disease-free areas of the peritoneal surface

were spared from resection.

All bowel anastomoses were constructed with hand-

sewn, two-layer closure, with two exceptions. Low colo-

rectal anastomoses and esophagojejunal anastomoses were

performed with the assistance of intraluminal staplers after

the peritoneal perfusion was completed.

HIPEC using the coliseum technique [12] with the

chemotherapeutic agent of choice was performed after all

resections were completed and before construction of any

suture lines. The apparatus for HIPEC included a kit

designed for a high-volume infusion and drainage; it was

composed of one inflow tube and three drainage tubes,

which were placed over the midline abdominal incision

through a small space between the skin and the plastic

covering sheet—one underneath each hemidiaphragm, and

one in the pelvis. This set was developed after some per-

sonal initial problems with closed suction drains. The

abdominopelvic perfusion was performed for 30–90 min

using a heat exchanger, two roller pumps, and a heater/

cooler unit. Three liters of 1.5% dextrose peritoneal dial-

ysis solution containing the chemotherapeutic agent was

Table 1 Patients’ characteristics

Characteristic No. of patients (n = 46)

Sex (M/F) 15/31

Age

Median 49

Range 18–77

Primary tumor

Colorectal cancer 13

Appendiceal cancer 8

Ovarian cancer 15

Mesothelioma 2

Other 8

PCI

Median 11

Range 1–25

Completeness of cytoreduction

CC-0 45

CC-2 1

PCI peritoneal carcinomatosis index, CC-0 complete cytoreduction,

CC-2 incomplete cytoreduction

836 World J Surg (2009) 33:835–839

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heated and infused at approximately 1 l/min. The temper-

ature was measured with a digital thermometer and was

kept between 42 and 43�C at the inflow line, averaging

41�C at the intraabdominal sites. Throughout the perfusion,

the surgeon continuously manipulated the viscera to dis-

tribute both heat and chemotherapy. A Tenckhoff catheter

was placed through the abdominal wall at the end of the

surgical procedure if early postoperative intraperitoneal

chemotherapy (EPIC) was planned.

Type of intraperitoneal chemotherapy

Patients with a colorectal primary cancer received mito-

mycin C (MMC) at a dose of 35 mg/m2 (maximum dose

70 mg) [13] or oxaliplatin at a dose of 460 mg/m2 [14].

Patients with ovarian or peritoneal malignant mesotheli-

oma received a combination of cisplatin (CDDP) at a dose

of 50 mg/m2 and doxorubicin at a dose of 10 mg/m2 [15,

16]. Gastric cancer patients received MMC ? CDDP

intraperitoneally at doses of 20 and 200 mg/m2 [17],

respectively. The details of the chemotherapeutic agents

used for each patient are detailed in Table 2.

All the patients were transferred to an intensive care unit

postoperatively for a median time of 24 h (6–264 h) and

then to the surgical department. The median hospital stay

was 17 days (range 6–57 days). Clinical, biologic, and

radiologic follow-up of the patients was done on a regular

basis after discharge from the hospital.

Statistical analysis

Data were collected and analyzed on a commercially

available computer program (version 12.0; SPSS, Chicago,

IL, USA) and are expressed as the mean, median, and

range. Kaplan–Meier tests were used for analysis of the

censored survival and recurrence rates.

Results

Peritonectomy results

At the end of the surgical procedures, complete cytore-

duction (CC-0) was obtained in 45 of the patients and

incomplete (CC-2) cytoreduction in one patient. The

median peritoneal carcinomatosis index (PCI) was 11

(range 1–25), and the median operating time was 17 h

(range 9–27 h) including the HIPEC.

There were no deaths related to the procedure. Major

postoperative morbidity, observed in 52% of the patients,

included fistulas, abscesses, and hematologic complications

(Table 3). The most significant were five spontaneous gas-

trointestinal perforations (one gastric, two small bowel, two

colonic), two digestive fistulas requiring surgical treatment,

four pancreatic fistulas, and one biliary fistula treated by

percutaneous drainage. Grade II/IV hematologic toxicity

occurred in six patients and systemic infection in five.

Survival results

The median follow-up was 20 months (range 1–

47 months). The 4-year overall survival rate was 56%

(Fig. 1). Ten patients had died, seven from recurrent dis-

ease, with a median disease-free interval of 16.3 months.

Among the 21 patients with peritoneal carcinomatosis

(PC) from colorectal origin, 9 (42%) had a recurrence, 3

with peritoneal disease. The 3-year and disease-free

Table 2 Chemotherapeutic agents and their duration of administration

Diagnosis Chemotherapeutic

agent

Dose

(mg/m2)

Duration

Colon and appendiceal CA

18 Patients Mitomycin C 35 90 min

3 Patients Oxaliplatin 460 30 min

Ovarian CA

(15 patients)

Cisplatin 50 90 min

Doxorubicin 10

EPIC paclitaxel 20 5 days

Gastric CA

(1 patient)

Mitomycin C 20 90 min

Cisplatin 200

Mesothelioma

(2 patients)

Cisplatin 50 90 min

Doxorubicin 10

EPIC paclitaxel 20 5 days

CA cancer, EPIC early postoperative intraperitoneal chemotherapy

Table 3 Complications

Complication No. of events

Pancreatic fistula 3

Anastomosis leak 2

Hematologic toxicity 6

Abdominal compartmental syndrome 1

Billiary fistula 1

Sepsis 5

Urinary fistula 2

Abdominal abscess 1

Gastroparesis 4

Abdominal bleeding 1

Spontaneous digestive tract perforation 5

Pulmonary complications 3

Renal failure 1

Pulmonary embolism 2

Congestive heart failure 3

World J Surg (2009) 33:835–839 837

123

survival rates were 70 and 35%, respectively. The 15

patients with PC from ovarian origin had an estimated 4-

year survival of 58%. Eight presented with recurrent dis-

ease, five of these in the peritoneum. The median disease-

free survival was 21 months, and the Kaplan–Meier 4-year

disease-free survival was 13%.

Discussion

During the past decade, a number of groups have reported

their results of cytoreduction combined with intraperito-

neal chemotherapy. The results from 385 patients affected

by appendiceal malignancies were published in 1999 and

showed a 5-year survival rate of 30% for patients with

appendiceal hybrid and mucinous adenocarcinoma [7]. In

a similar study, Loggie et al. [18] made a clear distinction

between patients who had complete cytoreduction and

those who had incomplete cytoreduction. In this study,

complete cytoreduction resulted in a median survival of

28 months, and those who had incomplete cytoreduction

survived a median of 10 months. Comparable results were

reported by Shen et al. [19]; their 3-year survival rate was

68% for patients who underwent complete cytoreduction

versus 21% survival rate for the others. Based on their

experience in Paris, Elias et al. [20] reported a 2-year

survival rate of 54%; and Beaujard et al. [21] in Lyon

found a median survival of 16 months in patients who

underwent successful cytoreduction. Piso et al. [22] found

a remarkable 4-year survival rate of 75%. Even in patients

with incomplete cytoreduction the 4-year survival rate

was 40%, and after complete cytoreduction it was 90%.

The Roman study of Cavaliere et al. [23] showed a 2-year

survival of 61%. At The Netherlands Cancer Institute, a

median survival of 22 months was found in a randomized

trial comparing cytoreduction plus HIPEC followed by

systemic adjuvant chemotherapy versus a 12.6 months’

median survival after palliative surgery and systemic

chemotherapy [13]. A 4-year survival rate of 55% was

observed in the present study, which includes all patients

treated for peritoneal carcinomatosis by cytoreduction and

HIPEC at Hospital Sirio Libanes, Sao Paulo, Brazil.

Appropriate selection of patients for cytoreduction and

HIPEC is difficult. The key issue is to select patients with a

satisfactory performance in whom it is feasible to attain

complete cytoreduction to maximize survival and minimize

the complication rates. The best way to identify those

patients is through laparotomy, in which PC is diagnosed

and quantified [24, 25]. It is therefore important that the

operative notes provide full details of the procedure during

which the carcinomatosis is diagnosed, including a full

description of the findings as well as an explanation of the

attempts made to explore the abdomen. A standardized

form on which operative findings can be reported would be

helpful.

Ironically, although the studies involving cytoreduction

plus HIPEC are conducted primarily by surgical groups,

not medical oncologists, a typical study on this subject

often provides the full data on the HIPEC itself, whereas

data on the surgery performed for cytoreduction are often

poorly presented. In our study, an attempt to provide the

extent of surgery is given by describing the median PCI

index. Our experience indicates that the small bowel and its

mesentery is the limiting factor for complete cytoreduction

and survival. Once it has been affected by PC, it indicates a

poor outcome, even when cleared of tumor. The reason for

this is that there is a minimal length of bowel that must be

preserved to maintain adequate nutritional and fluid uptake,

limiting the possibility of resecting all of the affected

bowel and mesentery.

The extent of the surgical procedure and the chemo-

therapic agent given intraperitoneally not only determines

the complication rate but also affects the remaining bowel

function. McQuellon et al. [26, 27] studied quality of life

after cytoreduction plus HIPEC and found no long-lasting

impairment of the quality of life after the procedure. This

probably means that the remaining abdominal function is

adequate for ‘‘normal’’ well-being [26, 27].

The question of what part of the treatment—cytore-

duction or HIPEC—is effective remains open to debate.

Based on a review of the literature, it is clear that a mac-

roscopically complete resection (CC-0) is a basic necessity

for a good outcome, with the evidence for HIPEC being

less compelling.

Recent developments in the medical treatment of stage

IV colon carcinoma and stage IIIC ovarian carcinoma have

brought promising results. These developments provide an

Fig. 1 Overall survival

838 World J Surg (2009) 33:835–839

123

opportunity to improve adjuvant treatment after HIPEC.

They also bring the opportunity to test newer agents in the

HIPEC setting.

Conclusion

Evidence is mounting that cytoreduction and HIPEC in

appropriate candidates can result in long-term survival for

those with peritoneal carcinomatosis of colorectal and

ovarian origin. Therefore, this treatment should be con-

sidered for all patients in whom complete cytoreduction of

the abdominal cavity is feasible. If complete cytoreduction

is not accomplished, the patient cannot be expected to

benefit from this treatment and so should be treated sys-

temically only.

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