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REVISIONES
Cytoreductive surgery and intraperitoneal
chemotherapy for the treatment of peritoneal
surface malignancy
C. Pablo Carmignani, Jesús Esquivel and Paul H. Sugarbaker
aDepartament
of Surgical Oncology. Washington Cancer Institute.
Despite new developments in the treatment of solid
tumors, complete resection remains as an absolute
requirement for cure of gastrointestinal cancer. Success in the surgical management of peritoneal surface malignancy depends on the surgeon’s ability to
complete complex cytoreductive procedures so that
only microscopic disease remains. This paper describes the current strategy that the surgical oncologist should pursue in the treatment of patients with
peritoneal carcinomatosis, sarcomatosis and mesothelioma. Technical details required for this surgery
include patient position, incision and exposure,
complete lysis of adhesions, electroevaporative dissection, peritonectomy procedures, proper positioning of drains for intraperitoneal chemotherapy,
and reconstructive surgery.
Understanding the treatment and mastery of surgical skills to manage the peritoneal surface spread of
malignancy has led to long-term survival of selected patients.
The success of this treatment strategy depends on a
long-term dedication to achieve the full potential of
a curative outcome.
Key words: peritoneal carcinomatosis, cytoreductive
surgery, intraperitoneal chemotherapy.
Carmignani CP, Esquivel J, Sugarbaker PH. Cytoreductive surgery and intraperitoneal chemotherapy for the treatment of peritoneal surface malignancy. Rev Oncol 2003;5(4):192-8.c
INTRODUCTION
Peritoneal seeding is one of the most frequent manifestations of treatment failure in patients with abdo-
Correspondence: Dr. P.H. Sugarbaker
Departament of Surgical Oncology
Washinton Cancer Institute
110 Irving Street Suite CG-185 NW
Washington, D.C. 20010
United States.
E-mail: [email protected]
Received 9 December 2002; Revised 12 March 2003; Accepted
21 March 2003.
192
Cirugía citorreductora y quimioterapia
intraperitoneal para el tratamiento de
la neoplasia en la superficie peritoneal
A pesar de los nuevos descubrimientos en el tratamiento de los tumores sólidos, la resección completa continúa siendo un requisito absoluto para lograr la curación del cáncer gastrointestinal.
El éxito del manejo quirúrgico de la neoplasia en la
superficie peritoneal depende de la habilidad del cirujano para realizar complejas resecciones eliminando todo vestigio neoplásico visible. Este artículo describe la estrategia actual que el cirujano oncológico
debería usar en el tratamiento de pacientes con carcinomatosis, sarcomatosis y mesotelioma peritoneales. Los aspectos técnicos del procedimiento quirúrgico consisten en posición del paciente, incisión y
exposición, completa lisis de adherencias, disección
electroevaporativa, peritonectomías, adecuado posicionamiento de drenajes para la quimioterapia intraperitoneal y cirugía reconstructiva.
Como consecuencia de la comprensión del tratamiento y del perfeccionamiento de las habilidades
quirúrgicas para manejar la siembra peritoneal del
cáncer, la sobrevida ha aumentado en pacientes seleccionados. Es indispensable una prolongada dedicación tendiente a aprovechar todo el potencial de
esta estrategia terapéutica.
Palabras clave: carcinomatosis peritoneal, cirugía citorreductora, quimioterapia intraperitoneal.
minopelvic malignancies. Despite curative surgery,
between 20% and 30% of the patients will develop local tumor recurrence1,2. Regional dissemination with
peritoneal implants has always been a therapeutic
challenge with most patients undergoing palliative
surgery or no surgery at all.
Peritoneal carcinomatosis and sarcomatosis may occur either concomitantly with the primary tumor or
as a recurrence after surgical resection. In the former,
malignant cell dissemination is spontaneous, following serosal invasion or perforation of the involved
organ. In the latter, it may be the consequence of in-
Rev Oncol 2003;5(4):192-8
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CARMIGNANI CP, ESQUIVEL J, SUGARBAKER PH. CYTOREDUCTIVE SURGERY AND INTRAPERITONEAL CHEMOTHERAPY FOR THE
TREATMENT OF PERITONEAL SURFACE MALIGNANCY
vasive diagnostic or therapeutic procedures (i.e. fine
needle aspiration, tumor rupture during an operation)3. Peritoneal seeding may occur even in the absence of hematogenous or lymphatic metastasis.
A positive peritoneal fluid cytology has been detected
in 25% to 30% of resectable gastric and colonic
tumors4-7. Surgical resection results in the release of
viable cancer cells in 50% to 60% of the patients8-10.
The disruption of the peritoneal membrane provides a
fertile area for peritoneal implants during inflammatory response period along with the healing process11.
Combined use of peritonectomy and perioperative intraperitoneal chemotherapy is aimed to complete eradication of the disease. This new approach requires
the acquisition of new technical skills to ensure safety
and efficacy.
STRATEGY FOR COMBINED TREATMENT
Peritoneal surface malignancy requires a new therapeutic strategy that can be divided in four steps: electrosurgery for tumor resection and peritonectomy,
hyperthermic intraperitoneal chemotherapy, reconstruction and early postoperative intraperitoneal chemotherapy. The use of adequate instruments and specific surgical techniques are essential to achieve
optimum results.
Electrosurgical dissection
Surgical dissection is performed using 3 mm ball-tipped monopolar electrosurgery. The electrosurgical
generator is set to pure cut, 200-250 MW.12 Tissues
are evaporated at the contact of the ball tip, minimizing blood loss from vessels up to 1.5 mm in diameter. Larger vessels are electrocoagulated or ligated in
continuity and divided. Intermittent saline irrigation
is utilized to decrease the risk of heat damage to adjacent tissues. Heat necrosis at the tumor’s margin of
resection could reduce the possibility of dissemination and cancer recurrence.
Chemotherapy
Agent’s selection for intraperitoneal chemotherapy is
based on the ability of the drug to produce a cytotoxic
effect over a short period of time and to show heat synergy. Mitomycin C, doxorubicin and cisplatin have a
low clearance from the abdominal cavity13-15. Pharmacokinetic studies on intraoperative intraperitoneal
chemotherapy showed 75% to 90% absorption of mitomycin C and cisplatin within the first hour16,17. Despite the enhanced cytotoxicity due to high concentrations and heat, this technique is effective only when
treating small volume peritoneal carcinomatosis.
Any anastomosis is constructed once intraoperative
intraperitoneal chemotherapy is finished. In this way,
00
intestinal stumps are exposed to heat and to cytotoxic
agent, preventing possible anastomotic recurrences.
The first 5 days of the postoperative period, patients
undergo a treatment with intraperitoneal chemotherapy through a Tenckhoff catheter using a different
agent. Currently, the drugs on use are 5-fluorouracil
or paclitaxel, depending on the primary tumor, its
histologic characteristics, previous systemic or intraperitoneal chemotherapy and the response to these
treatments. This stage of the treatment may be restricted in some patients, due to concomitant conditions or when the postoperative chemotherapy may
increase importantly the morbidity of the procedure.
Safety
The occupational risk of the personnel exposed to
long-term, low-dose cytotoxic agents used in the operating room remains unknown. Nevertheless, to date,
research suggests no significant risk18. Guidelines for
administration and manipulation of such agents are
available19. The safety of all personnel in the operating room is paramount. The use of eye protection,
double gloving with outer elbow-length gloves secured with sterile tape and impervious gowns are essential to protect the operator. Incorporation of a plastic cover within the sutures to the skin edge prevents
droplet contamination. A smoke evacuation system
removes steam from the chemotherapy in the abdominal cavity.
INDICATIONS AND CONTRAINDICATIONS
This therapeutic approach has been successfully employed in patients with peritoneal dissemination of
primary peritoneal tumors, like peritoneal mesothelioma; in patients with tumors of the gastrointestinal
tract like appendiceal, colonic and gastric cancer, and
in selected cases of peritoneal sarcomatosis.
This treatment is contraindicated in four well defined
situations: when there is evidence indicating that the
patient may not survive the procedure, when there
are liver or extra-abdominal metastasis or when the
computed tomography (CT) scan shows signs of segmental small bowel obstruction. If none of these stop
signs is present and the surgeon finds during the operation that it would be impossible to re-establish intestinal function, he or she should perform the best
possible surgical palliation.
OPERATIVE PROCEDURE
Patient position
Careful positioning of the patient on the operating table is crucial to avoid complications related to areas
of pressure, since this is a procedure that can last 10
to 12 hours. We advocate the lithotomy position, with
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CARMIGNANI CP, ESQUIVEL J, SUGARBAKER PH. CYTOREDUCTIVE SURGERY AND INTRAPERITONEAL CHEMOTHERAPY FOR THE
TREATMENT OF PERITONEAL SURFACE MALIGNANCY
open legs, thighs flexed 15° on the abdomen and legs
flexed 30° on the thighs. The legs are supported by St.
Mark’s leg holders (AMSCO, Erie, PA, USA) surrounded with alternating pressure devices (SBC Compression boots, Kendall Co., Boston, MA, USA) and protected from decubitus lesions by egg crate foam padding.
The weight of the lower extremity is on the heel and
not on the calf or popliteal crease.
Exposure
A vertical xiphopubic incision is made to allow maximum exposure; the xiphoid process is usually excised. During re-operation, old surgical scar is resected
from the skin through the peritoneum, including umbilicus, to excise any implant in scar tissue20,21. A selfretaining retractor (Thompson Surgical Instruments,
Inc., Traverse City, MI, USA) allows multiple angles of
retraction to gain maximum exposure for peritonectomy (fig. 1).
Peritonectomy
All visible tumor should be excised in order to obtain
maximum benefit from intraperitoneal chemotherapy. Peritonectomy techniques make possible to resect any disease involving parietal peritoneum. Small
nodules can be electroevaporated but bigger nodules
must be resected (fig. 2).
Electroevaporative
surgery
Small implant
adenocarcinoma
Result
Intraperitoneal
chemotherapy
Large implant
adenoarcinoma
Fig. 2. The small nodules (≤ 7 mm) usually do not invade
beyond the muscular layer and allowing their electro-evaporation from the surface of the small bowel. Nodules bigger than the mentioned size invade the full thickness of the
bowel wall. In such cases, electro-evaporation is too risky.
Self-retaining
retractor
Lessea
omentum
Greater
omentum
Right and left upper quadrant peritonectomy
Falciform and triangular ligaments are resected at the
start of the operation. In right upper quadrant peritonectomy, peritoneum is stripped from the posterior
rectus sheath in continuum. Dissection extends to the
bear area of the liver. In case the tumor is advanced
and has an invasive component, peritoneal stripping
of the tendinous portion of the diaphragm may result
in penetration into the pleural cavity. Tumor nodules
sitting on the surface of the liver should be electroe-
Fig. 1. Abdominal incision and self-retaining retractor position.
Right
hemidiafragm
Centripetal surgery
Peritoneal stripping begins in the medial line and proceeds in a circumferential fashion towards the deepest
areas of the tumor and the major vessels. A coordinate
effort includes up to 6 peritonectomy procedures. It is
necessary to allow optimum clearance and containment of the tumor with minimal bleeding and no damage to vital structures. Rectal muscle should be preserved, but occasionally the posterior rectus sheath
may be sacrificed.
194
Peritoneum
involved
Fig. 3. Peritonectomy of the right upper quadrant.
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CARMIGNANI CP, ESQUIVEL J, SUGARBAKER PH. CYTOREDUCTIVE SURGERY AND INTRAPERITONEAL CHEMOTHERAPY FOR THE
TREATMENT OF PERITONEAL SURFACE MALIGNANCY
vaporated, sometimes going beyond the Glisson’s capsule. In the left upper peritonectomy, the stripping
away of the peritoneum will expose the left hemidiaphragm muscle and tendon, left adrenal gland,
distal portion of the pancreas and the cephalic portion of the perirenal fat. Care is taken with the left
gastric artery and coronary vein to protect the vascular supply of the stomach (fig. 3).
Greater omentectomy and splenectomy
The greater omentum is involved early in tumor dissemination within the abdominopelvic cavity and its
removal is important to reduce risk of recurrence
even if this structure appears normal. The greater
omentum is resected to include the branches of the
gastro-epiploic vessels on the greater curvature of
the stomach and the short gastric vessels. All vessels
are ligated and divided on the surface of the stomach.
Early mobilization of the omentum improves exposure and enables an adequate visual assessment of the
abdominal cavity, especially of the lesser sac. A splenectomy is performed to include the complete removal of tumor deposits on the anterior fascia of the
pancreas and on the splenic hilus.
Pelvic peritonectomy and rectosigmoidectomy
It includes peritoneal stripping from the right and left
caudal portions of the abdominal wall, the bladder
and resection of rectosigmoid portion of large bowel
along with their mesenteries from the origin of the inferior mesenteric artery. Stripping the peritoneum up
to the duodenum and ligament of Treitz completes
the peritonectomy and facilitates ligation of the inferior mesenteric artery and vein. In women a hysterectomy and bilateral salpingoophorectomy is performed. The subperitoneal rectum and apex of vagina in
women are removed en-bloc including all the neoplastic tissues in the peritoneal cul-de-sac. Closure of
the vagina is necessary before the intraoperative chemotherapy is initiated. Special care should be taken
in order to avoid injuries to the ureters, bladder and
pre-sacral and iliac vessels (fig. 4).
Cholecystectomy, lesser omentectomy, and
stripping the floor of the omental bursa
Cholecystectomy is performed from the fundus; the
structures of the porta hepatis are dissected free of tumor by a spreading clamp. Tumor from the anterior
surface of the left caudate lobe process is electroevaporated and the gastrohepatic ligament is excised in
resection of the lesser omentum. Care is taken with
the left gastric artery and vein to protect the vascular
supply of the stomach.
After tumor resection, the abdominopelvic cavity is
vigorously lavaged by many liters of warm saline solution aimed at mechanically eliminating viable cancer cells from fibrin and blood clots. The removal of
fibrin and blood clots also helps reduce the risk of
postoperative adhesions.
OPEN HYPERTHERMIC INTRAPERITONEAL
CHEMOTHERAPY
Wide ligament
(ligated)
Douglas
Pouch
Ovaric vessels
(sectioned)
Ureter
Inferior mesenteric
artery (ligated)
Fig. 4. The line shows the location of the incision for a
comprehensive pelvic peritonectomy.
00
Hyperthermia optimizes the dose intensity of chemotherapy to the abdominal and pelvic surfaces. The
combined use of hyperthermia and intraperitoneal
chemotherapy has enhanced the cytotoxicity of the
chemotherapeutic agents and increased tissue penetration by chemotherapy in cancerous as compared to
normal tissue.
Chemotherapy solution is administered with the abdomen open. To keep temperature to constant 42°C,
the solution is pumped by two rolling pumps through
a heat exchanger; then, through a Tenckhoff catheter
reaches the peritoneal cavity. The hyperthermic perfusate comes-off the abdomen through four JacksonPratt drains going back to the heat exchanger, closing
the circuit. The Tenckhoff catheter and the JacksonPratt drains are secured watertight with purse-string
sutures on the skin of the abdomen to avoid leaks and
spillage. Before starting the chemotherapy perfusion
the system is tested and primed for leaks using one liter of 1.5% of dextrose peritoneal dialysis solution. Finally, three liters of chemotherapy solution are used
Rev Oncol 2003;5(4):192-8
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CARMIGNANI CP, ESQUIVEL J, SUGARBAKER PH. CYTOREDUCTIVE SURGERY AND INTRAPERITONEAL CHEMOTHERAPY FOR THE
TREATMENT OF PERITONEAL SURFACE MALIGNANCY
to lavage the peritoneal cavity during 90 minutes at
42°C.
RECONSTRUCTION OF THE ALIMENTARY
TRACT AND CONSTRUCTION OF OSTOMIES
Any anastomosis or ostomy is performed once the heated intraoperative intraperitoneal chemotherapy is
finished. Patients that undergo a gastrectomy as part
of the cytoreductive surgery, receive a duodenal exclusion operation to protect the esophagojejunostomy.
The jejunum is transected 20 cm distal to the ligament of Treitz and its proximal portion is exteriorized
to divert biliopancreatic fluid. The distal portion of
the jejunum is anastomosed with the esophagus
using a circular stapler (Ethicon ILS 29, Cincinatti,
OH, USA).
Before closure the Tenckhoff catheter is placed in the
left upper quadrant close to the ligament of Treitz or
in the right subdiaphragmatic space. Drains are placed in the pelvis cavity and subdiaphragmatic spaces.
Chest tubes are inserted in pleural spaces when stripping of undersurface of diaphragm was performed.
The abdomen is then closed in the usual fashion. Skin
is sutured with a nylon running suture to decrease
the likelihood of chemotherapy spillage during postoperative intraperitoneal chemotherapy. One last drain
is positioned in the subcutaneous tissue.
EARLY POSTOPERATIVE INTRAPERITONEAL
CHEMOTHERAPY
It is indicated following the complete resection of appendiceal, colorectal, gastric or other gastrointestinal
carcinomas. Approximately 24 hours after cytoreductive surgery early postoperative intraperitoneal chemotherapy is initiated and the drains are closed for
23 hours. The abdomen is then drained for one hour
until next chemotherapy infusion. This is repeated for
5 consecutive days. Table 1 summarizes the indications for perioperative intraperitoneal chemotherapy
in the colorectal cancer setting.
TABLE 1. Indications for perioperative intraperitoneal
chemotherapy in colorectal cancer
Positive peritoneal cytology
Invasion or metastasis to the ovaries
Seeding to the colonic serosa
Rupture of a necrotic tumoral mass
Invasion to adjacent organs
Intraoperative peritoneal dissemination
Primary tumor perforation
Lymph node metastasis in the resection margin
Limited peritoneal seeding with a peritoneal cancer index <20
Completeness of cytoreduction score 0-1
Advanced primary mucinous tumor
Modified from Cancer Chemother Pharmacol23.
196
1
2
3
8
0
4
7
6
5
Regions
0 Central
1 Right superior
2 Epigastrium
3 Left superior
4 Left flank
5 Left inferior
6 Pelvis
7 Right superior
8 Right flank
9 Proximal yeyunum
10 Distal yeyunum
11 Proximal ileum
12 Distal ileum
11
9
10
12
Score of size of lesion
LS0 No visible tumor
LS1 Tumor until 0.5 cm
LS2 Tumor until 5 cm
LS3 Tumor bigger than
5 cm or tumoral
confluency
Fig. 5.Tumor volume as assessed by the lesion size score
is determined for the 13 abdomino-pelvic regions. The sum
of these scores (0-39) is the peritoneal cancer index.
PERITONEAL CANCER INDEX
The peritoneal cancer index is a quantitative prognostic score calculated after abdominal exploration and
complete adhesiolysis. The success of complete cytoreduction and long-term survival can be predicted by
grading the distribution and the mass of peritoneal
surface cancer22. It is not useful, however, in grading
minimally invasive tumors such as pseudomyxoma
peritonei or cystic mesothelioma. In patients with peritoneal seeding from colon cancer, a score of 20 or
less had a year survival of 50%, from 11-20 a survival
of 20% and a score greater than 20, survival of 0%
(fig. 5).
CYTOREDUCTION SCORE
Another quantitative prognostic score is the completeness of cytoreduction. For gastrointestinal cancer, the
completeness of cytoreduction score has been defined
as follows: CC-0, no visible peritoneal carcinomatosis
remained after cytoreduction; CC-1, tumor nodules
persist after cytoreduction but less than 0.25 cm; CC-2
tumor of 25 to 2.5 cm; CC-3 tumor greater than 2.5 cm
or confluence of tumor unresectable at any site (fig. 6).
Patients with complete cytoreduction have a higher
chance of long-term survival, but incomplete cytore-
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CARMIGNANI CP, ESQUIVEL J, SUGARBAKER PH. CYTOREDUCTIVE SURGERY AND INTRAPERITONEAL CHEMOTHERAPY FOR THE
TREATMENT OF PERITONEAL SURFACE MALIGNANCY
DISCUSSION
Citoreduction index
(after resection)
CC-0
CC-1
No evidence Evidence
of disease of disease
CC-2
0.25 cm
0.25 cm
CC-3
2.5 cm >2.5 cm
Fig. 6. Completeness of cytoreduction after surgery
duction have a higher chance of long-term survival,
but incomplete cytoreduction rarely offers cure. In
patients with peritoneal seeding from colon cancer a
complete cytoreduction had a 40% 5-year survival;
patients with an incomplete cytoreduction had a 0%
5-year survival23. No patient with long-term survival
has been reported undergoing surgery alone or surgery plus systemic chemotherapy.
POSTOPERATIVE COMPLICATIONS
Careful patient selection is crucial for the success of
this treatment. The most common postoperative complications are prolonged intestinal ileus and gastric
paresis. Nasogastric suction is maintained until there
is evidence of bowel function. Total parenteral nutrition is needed until full caloric and proteic intake is
achieved. About one fifth of the patients require parenteral feeding at home.
In the most recent study of 200 patients who had undergone cytoreductive surgery and heated intraperitoneal chemotherapy for peritoneal carcinomatosis,
25% of the patients had complications grade III and
IV. Mortality rate was less than 2% (3/200). Most frequent complications were peripancreatitis (7.1%) and
bowel fistula (4.7%)24. Acute postoperative peripancreatitis, a potentially life-threatening condition, occurs more frequently if the peritoneum and fat are
stripped from the surface of the pancreas. If the patient presents with fever, peripancreatitis should be
ruled out. Along with the routine blood sample, a
sample from the material in the left upper quadrant
drain should be sent for lipase and amylase levels.
SECOND-LOOK OPERATION
A second-look with closure of a diverting jejunostomy
or ileostomy is routinely performed at 6-9 months in
one third of the patients. Eighty percent of the patients are found to have recurrences but have a complete redo-cytoreduction in 80% of the cases because
of the low peritoneal cancer index.
00
The successful management of peritoneal surface
malignancy depends on several factors: the presence
of co-morbid conditions, the disease stage, tumor biology, the completeness of cancer excision and the elimination of minimal residual cancer by chemotherapy. The higher success rates associated with the
treatment of cystadenocarcinoma, cystic mesothelioma and low-grade sarcomas are attributable to their
expansive growth, with minimal invasion of the underlying structures. Poorer results were obtained with
the treatment of adenocarcinoma, probably related
to the invasive nature of these tumors. Incomplete peritonectomies result in early recurrence and treatment failure.
The surgical procedure for the management of peritoneal malignancies poses a steep learning curve. It is
technically and physically demanding with long operative time and a risk of excessive blood loss. Furthermore, the administration of early postoperative intraperitoneal chemotherapy may be compromised by the
patient’s postoperative status. These factors may contribute to poor treatment outcome during the early
stages of a program in treating peritoneal surface malignancy and may deter many surgeons25. However,
the use of electroevaporative surgery has revolutionized the radical excision of peritoneal malignancies by
minimizing blood loss.
The pharmacokinetics advantages to intraperitoneal
chemotherapy have been well described. The success
of intraperitoneal chemotherapy is dependent on the
elimination of residual cancer cells following complete resection. However, the benefit of intraperitoneal
chemotherapy is localized to the surface area of infusion. Drug diffusion occurs but the tissue penetration
is limited to 1-2 mm from the surface26-28. We believe
that the open technique is superior to the closed technique in allowing adequate and uniform exposure of
all abdominal and pelvic surfaces to intraperitoneal
chemotherapy, as demonstrated by dye studies. In
contrast, many areas are unstained with dye when
the closed technique is employed, especially the lesser omentum, the base of the mesentery, the pelvis
and the suture lines. As a result, recurrence of tumor
often occurs on these sites of poor chemoperfusion20.
SUMMARY
Traditionally, peritoneal surface malignancy was regarded as a terminal condition for which surgery was
indicated only as a palliative effort. Advances in cytoreductive surgery and perioperative intraperitoneal
chemotherapy have improved the surgical approach
for this condition23,25,29-32. Also, new evidence from
tumor biology research suggests that peritoneal carcinomatosis, sarcomatosis and mesothelioma may oc-
Rev Oncol 2003;5(4):192-8
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CARMIGNANI CP, ESQUIVEL J, SUGARBAKER PH. CYTOREDUCTIVE SURGERY AND INTRAPERITONEAL CHEMOTHERAPY FOR THE
TREATMENT OF PERITONEAL SURFACE MALIGNANCY
cur without systemic dissemination, which has sparked new interest in these conditions. Curative treatment for peritoneal surface malignancies requires a
complete cytoreduction followed by intraperitoneal
chemotherapy. The careful selection of patients for a
complete cytoreduction with curative intent vs. appropriate surgical palliation remains a crucial component of management to ensure that patients with
unresectable disease receive an adequate palliation.
This paper describes the current strategy for the management of patients with peritoneal carcinomatosis,
sarcomatosis and mesothelioma. The relevant technical details specific to this form of treatment include
patient position, incision and exposure, electroevaporative dissection, complete lysis of adhesions, peritonectomy procedures, reconstructive surgery and intraperitoneal chemotherapy.
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