1. The Role Of Cytoreductive Surgery
and HIPEC in Peritoneal surface
Malignancy With Ovarian origin
Dr. ABDULAZIZ ALZAHRANI

2. INTRODUCTION AND LITERATURE
2
- Cancers originating from organs in the peritoneal cavity
account for approximately 250,000 new cancer cases annually in
the USA.
- The peritoneal cavity is a common site for metastases owing to
locoregional spread.
- Ovarian cancer with peritoneal involvement when treated with
aggressive surgical debulking combined with intravenous
chemotherapy is yielding ,unlike the nongynecological
malignancies.

3. INTRODUCTION AND LITERATURE
Ovarian cancer is the fifth leading
cause of cancer death in females.
Epithelial ovarian cancer accounts
for the majority of ovarian cancers
(>75%).
The diagnosis is often delayed
because of the nonspecific nature
of its presenting symptoms.

4. INTRODUCTION AND LITERATURE
The prevalence of advanced stage disease with
peritoneal and distant metastasis (FIGO stage
III/IV) is high, with the chance of cure being low
The overall 5-year survival rate of patients with
ovarian cancer of all stages is 43%, and it
decreases to <22 % in patients with advanced
disease.
Ovarian cancer spreads through exfoliation of
malignant cells into peritoneal fluid,
disseminating along the abdominal and pelvic
peritoneum

5. INTRODUCTION AND LITERATURE
Although ovarian cancer is often responsive to
initial maximal cytoreductive surgery (CRS)
and platinum-based chemotherapy, there
remains a high rate of recurrence(up to 70%)
and poor long-term survival.
Maximal cytoreductive surgical efforts against
recurrent ovarian cancer have been shown
to be independently associated with
improved overall survival.
.

6. INTRODUCTION AND LITERATURE
Intraperitoneal (IP) chemotherapy, given by infusion of
chemotherapeutic agents directly into the peritoneum, has been
investigated;
- Demonstrated an improvement in overall and
disease-free survival.
Two forms of IP chemotherapy may be delivered:
1 -Postoperative adjuvant IP chemotherapy delivered as adjuvant
treatment after recovery from CRS
2 -Intraperitoneal chemotherapy delivered as a heated
chemoperfusate intraoperatively .
.

7. INTRODUCTION AND LITERATURE
Postoperative adjuvant IP chemotherapy:
-Evaluated in several RCTs and has
demonstrated an improvement in overall
and disease-free survival.
.

8. INTRODUCTION AND LITERATURE
Intraoperative intraperitoneal chemotherapy : :
- known as hyperthermic intraperitoneal chemotherapy
(HIPEC).
-A recent systematic review on the combination of CRS
and HIPEC in ovarian cancer shows significant
potential benefits in disease-free and
overall survival rates
-Showed acceptable rates of morbidity and mortality including
platinum resistant cases.
.

9. INTRODUCTION AND LITERATURE
Intraoperative intraperitoneal chemotherapy : :
- Recently, Spiliotis et al. in a phase III prospective trial
evaluated the role of CRS and HIPEC plus systemic
chemotherapy versus CRS plus systemic
chemotherapy in women with recurrent EOC after
initial debulking surgery and systemic chemotherapy.
- The median survival rate was 19.5 months versus 11.2
months ( P < 0.05)
- The three-year survival was 50% versus 18% in favor of
the HIPEC group .
.

11. Peritoneal shedding of tumor cells
. Free intraperitoneal tumor emboli as a result of full thickness
invasion of the bowel wall by cancer.
. Leakage of malignant cells from transected lymphatic channels.
. Dissemination of malignant cells from trauma as a result of
dissection at a narrow margin.
. Blood clots that remain in the abdomen or pelvis that contain
viable cancer cells;.
. Fibrin entrapment of intraabdominal tumor emboli on
traumatized peritoneal surfaces.
. Tumor promotion of these entrapped cells through growth factors
involved in the wound healing process

12. • Passive Mode.
– Gravity
– Respiratory movements
– Peritoneal recesses
• Active movement
How do cancer cells move in the peritoneal
cavity?

19. Peritonectomy :
-An attempt to do complete
Cytoreduction of the malignant
peritoneal involvement by stripping
the involved parietal peritoneum
and ablation or resection of the
involved visceral peritoneum.
Definitions :

20. Definitions :
cont.
:PCI
- Peritoneal Cancer Index
-A score used to assess the feasibility of
Cytoreductive Surgery .
- Scored from 0 to 39 .
- Preoperative PCI (Radiological) .
- Intraoperative PCI .

21. Definitions

22. Peritoneal Surface Disease Severity Score
• PSDSS I < 4, PSDSS II = 4–7, PSDSS III = 8–10,
and PSDSS IV > 10

23. Definitions :

24. Rationale for Hyperthermic Intraperitoneal
Chemotherapy (HIPEC)
- In the treatment of peritoneal malignancies, it
is well known that there will be at least residual
microscopic cancer cells remaining in the
peritoneal cavity after the surgical procedure.
-Residual disease < 2.5 mm is amenable to
destruction by HIPEC and that counts for CC0 and
CC1 .

25. • IP Chemotherapy
– Pharmacokinetic argument:
- Peritoneal-plasma barrier makes higher
dose
. Of cytotoxic agents feasible(MMC 40 times)
– Maximal effect immediately after
. cytoreduction
– Limited systemic resorption / toxicity
Rationale for Hyperthermic Intraperitoneal
Chemotherapy (HIPEC)

26. • IP Chemotherapy
• Hyperthermia
– Pharmacodynamic argument;
- increased drug penetration
– Selective cytotoxicity of hyperthermia
– Synergism with chemotherapy
Rationale for Hyperthermic Intraperitoneal
Chemotherapy (HIPEC)

27. Rationale for Hyperthermic Intraperitoneal
Chemotherapy (HIPEC))
So , the advantages of HIPEC in the treatment of
peritoneal malignancies are numerous;
1) The residual malignant cells are directly exposed
to higher doses of chemotherapy than would be
possible with systemic chemotherapy.
2) The addition of heat, which potentiates the
chemotherapy, also increases its penetration into
malignant cells.
Heat itself is preferentially cytotoxic to malignant
cells.
3) Toxicity of the chemotherapy agents is not an
issue for the patient, as these are delivered while
the patient is under general anesthesia.

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31. 31

39. Gastrointestinal Cancers Symposium2012ASCO,
J Clin Oncol 30, 2012
Early and long-term outcome data on 2,298 patients with
pseudomyxoma peritonei treated by a strategy of cytoreductive
surgery and hyperthermic intraperitoneal chemotherapy.
2298 patients from 16 specialized units underwent CRS
&HIPEC for PMP.
-Mortality was 2%
-Major operative complication was 24%
-The median survival was 196 months
-The median progression-free survival was 98 months
5-,10- and 15-year survival rate of 78%, 63% and 59%
respectively

40. Gastrointestinal Cancers Symposium2012ASCO,
J Clin Oncol 30, 2012
Early and long-term outcome data on 2,298 patients with pseudomyxoma peritonei treated by
a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Independent predictors for a poorer progression-free survival are;
-PMCA histopathological subtype (P<0.001)
-Major postoperative complication (P=0.008)
-High PCI (P=0.013)
-Debulking surgery (CCR2/3) (P<0.001)

41. Gastrointestinal Cancers Symposium2012ASCO,
J Clin Oncol 30, 2012
Early and long-term outcome data on 2,298 patients with pseudomyxoma peritonei treated by
a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Independent predictors of a poorer overall survival are;
-Older age (P=0.006)
-Major postoperative complication (P<0.001)
-Debulking surgery (CCR2/3) (P<0.001)
-Prior chemotherapy treatment (P=0.001)
-PMCA histopathological subtype (P<0.001)

42. • 301 Patients from 18 French-speaking
centres
• 109 females and 111 males
• Mean age 52
• PMP from appendix 91%, ovary 7%
• Mean PCI 18.5

43. 43

44. 44

45. 401 Patients
Median Follow-Up 33 months
(range 1 to 235 months)
Epithelioid - 318 (79%)
Mean PCI – 20
CC0/1 – 187 (46%)
HIPEC – 372 (92%)

48. Patients with epitheloid tumors with complete (CC0) cytoreduction
Median
Survival
87 months

49. •- 23 articles reporting M&M from various
peritonectomy units were reviewed.
•- Institutions categorised between high and
•low volume

50. Mean ICU Stay = Range from 1 to 5
Mean Hospital Stay = Range 7 to 48
Overall Mortality = 0 to 17%
High Volume Centres
Mortality rates ranged 0.9% to 5.8%

51. • Between January 1997 and October 2008
• 243 consecutive patients undergoing CRS and
HIPEC for PMP
• Complications assigned based on NCI CTC

52. NCI - CTC
• Grade 0 – no complication
• Grade 1 – minor complication self remediating
• Grade 2 – complication requiring medical
therapy
• Grade 3 – complication requiring invasive
radiological intervention
• Grade 4 – complication requiring re-operation

54. French Multicentre Data
n = 1290
25 centres
Case volume Total Pts
Institution 1 403 403
3 100-300 450
3 50-100 225
4 20-50 100
5 10-20 75
6 <10 45

55. Drill Down PMP French Study
Centre 3Yr 5Yr
Best 87 77
Worst 47 45
Elias + Assoc F de Chir EJSO 2010

56. What is the learning curve about?
Selection
Decision Making
Technical Factors
Team (Nurse, Anaesthetist, ICU,
Oncologist, Radiology)
MDT

57. PATIENT SELECTION
The outcome of CRS is affected variably by;
- Patient conditions.
Age,nutrition , performance , comorbidities
- Disease volume.
PCI
- The biological behavior of the tumor
. low grade VS high grade.
. propensity to spread by direct peritoneal
attachment and proliferation VS
lymphatic and hematogenic.

58. Selection Protocol
PMP DPAM - Any Vol
PMCA (Angio CT, PET) Signet
CRC PCI <20, +/- Liver <4, Diff, Signet
(Angio CT, PET, ?Laparoscopy)
Meso Epith ? No Sarcomatoid (Angio CT, PET)
Ovarian Recurrent disease (Angio CT, PET)
Gastric PCI <10 (Angio CT, PET, Laparoscopy)
Redos PMP. Meso
?CRC

59. MDT MEETING
Radiology
Surgery
Oncology
ICU
Records

60. Consent/Education
Information Book
Education
More than 1 person to consent
Other patients

61. CHEMOTHERAPY PROTOCOL
and sarcomamesotheliomaFor ovarian cancer,
1. Add cisplatin (50 mg/m²) ________ mg to 2 liters of 1.5% dextrose peritoneal
dialysis solution. Add doxorubicin (15 mg/m²) _______ mg to same 2 liters of 1.5%
dextrose peritoneal dialysis solution.
2. Add ifosfamide (1300 mg/m²) ________ mg to 1 liter 0.9% sodium chloride.
Begin continuous IV infusion over 90 minutes simultaneously with IP chemotherapy.
3. Add mesna disulfide (260 mg/m²)________ mg to100 ml 0.9% sodium chloride to
be given IV as a bolus 15 minutes prior to ifosfamide infusion.
4. Add mesna disulfide (260 mg/m²)________ mg to 100 ml 0.9% sodium chloride to
be given IV as a bolus 4 hours after ifosfamide infusion begins.
5. Add mesna disulfide (260 mg/m²)________ mg to 100 ml 0.9% sodium chloride to
be given IV as a bolus 8 hours after ifosfamide infusion begins.
6. Send all the above to operating room #________ at ________ o’clock on
___________ (Date) for a 90-minute treatment.

62. CHEMOTHERAPY PROTOCOL
and sarcomamesotheliomaFor ovarian cancer,
)5-1(postoperative daysPaclitaxel
1. Paclitaxel __________ mg (20-40 mg/m2 x __________ m2) (maximum dose: 80
mg) in __________cc 6% Hetastarch (B. Braun, Irvine, CA) via IP catheter on
_________________. Last dose _________.
2. Infuse as rapidly as possible via Tenckhoff catheter. Dwell for 23 hours. Drain from
Tenckhoff x 15 minutes before draining all catheters for one hour prior to next
instillation.
3. Use 1 liter 6% Hetastarch for body surface 1 - 2 m2, 1.5 liters for body surface >
2.0 m2.
4. Continue to drain abdominal cavity after last dose until Tenckhoff catheter is
removed.
5. During initial 6 hours after chemotherapy infusion, patient's bed should be kept
flat. The patient should be on the right side during infusion. Turn at ½-hour post
infusion onto the left side and continue to change sides at ½-hour intervals for 6
hours.
6. Monitor with pulse oximeter during the first 6 hours of intraperitoneal
chemotherapy

63. Peritonectomy Techniques
Open vs closed
position:
Modified lithotomy position is achieved with the legs
extended in St. Mark's leg holders.
.

64. Peritonectomy Techniques
Procedure :
-Long midline incision.
-After full exposure of intraperitoneal cavity, tumour burden is
checked .
-In PMP & Ovarian tumours , if > more than 1.5 m of small bwoel
can be saved > Go ahead .
-In other diseases > PCI then decide.
Which is first ?
-If liver and rt upper quadrant is extensively involved > start there.
-If liver and rt upper quadrant involvement is not bad > start in the
pelvis(almost always extensively involved)

65. Peritonectomy Techniques
Bookwalter or Thompson ,Argon beam, CUSA, Smoke
evacuator ,Ball-tip (3mm)
Total anterior parietal peritonectomy
.

66. Peritonectomy Techniques
Total anterior parietal peritonectomy
Then > greater omentectomy, and splenectomy.
>Right upper quadrant peritonectomy
right hemidiaphragm,
right subhepatic space
the surface of the liver
Cholecystectomy
stripping of the hepatoduodenal ligament
resection of the falciform ligament

67. Peritonectomy Techniques
> Left upper quadrant peritonectomy
Left hemidiaphragm peritoneal striping
? Total or partial gastrectomy and reconstruction
?Resection of the tail of the pancreas
.

68. Peritonectomy Techniques
> Pelvis
Hysterectomy
transection of the
rectum beneath the
peritoneal reflection
> Small bowel and mesentry
Marking stitches

73. Peritonectomy Techniques
At the end of peritonectomy > secure hemostasis
wash thoroughly
Then > Chemo setting
Coliseum Technique;
.

76. 76

77. The Peritonectomy Unit
At KAMC
The Story Of The Start

78. Establishment Stages
•With medical oncology:
•1- Convince them that we are able to operate(mortality
and morbidity issues)
•
•2-Bring our evidence on:
•Patient &personnel safety
•Survival benefits
•No more high morbidity and mortality procedure.
3- Get them to write the IP Chemo protocool.
Success and then discussed cases in tumor board and
peritonectomythen we have patients listed for

79. •OR stage:
•We need a special set up.
•-Hyperthermia perfusion pump + the disposabe circuits
for HIPEC (BELMONT)
•-Train perfusionest
•-Make sure that Chemo is prepared in large bag of 3 liters
of Dianel 1.5(we are the only center to have it in the KSA)
•Special retracor system( Bookwalter and Thompson with
long side vertical bars)……..not optimal…..we modified our
tecneque.(good)
•Special sterile plastic drapes for isolation……….Available
•Jet smoke evacuator with ball diathermy to coagulate at
100-120
•-Argon beam ,CUSA for liver resections and ablations.
•…………………………………………………………Every thing is available

80. Anaesthesia special preparation:
•- Got the protocol for anaesthesia during
HIPEC.
•- Cooling measures to overcome HIPEC
hyperthermia(42-44 c) otherwise ,patient
brain will be cooked easily.
•cooling mattress
•Ice bags around neck,axilla ,
groin, etc.
•-Continuous monitor of core temp

81. Getting Started
•The first case:
•-63 yrs female
•-PMP …..Very high volume diease and redo
surgery debulked three times in other
hospitals.
•-PCI of 39 , badly symptomatic with
respiratory compromise due the tense
abdominal distension .
•Option for her is either surgery or DNR.

82. •Operation done……> HIPEC went smooth
•>21 hrs
•> 15 kg of tumor is out
•>8 units of PRBCS
•
•Did well except morphia adiction issues and
rising bilirubin level ,liver biopsy > CASH.
•2 months later > CVA ,aspiration pneumonia and
DIC. > Death

83. 2nd case :
42 yrs male
Healthy otherwise
Low volume peritoneal
carcinomatosis(appendex )
Tumor Board > for CRS &HIPEC
Operation…..(peritonectomy ,omentectomy, Rt diaphragm and pelvic
stripping +HIPEC withmitomycin c for 90 minutes.
-7 hrs
--No blood transfusion
-- No EPIC - Sort hospital stay
-- 6 months later . No recurrence.

84. 3rd case
47 yrs male
PMP (high volume disease )
PCI> 30
PROCEDURE > peritonectomy omentectomy
distal gastrictomy distal pancreatetomy splenectomy
hepatic metastatectomy sig 1,2,6 porta hepatis and
caudate lobe dissection resection of falciform lig.
Cholecystectomy subtotal colectomy bilateral
diaphragmatic and pelvic peritoneal stripping multiple
segmental small bowel resections.
Then HIPIC wit Mitomycin c.
-19 hrs
6 units of PRBCS
Post Op did well
Now , he is disease-free with good quality of life.> 13
months

88. 4TH case
•49 yrs male
•Rectosigmoid ca with peritoneal mets
•Radiological PCI >10
•Operative PCI 17
•Neoadjuvent chemo.
•Surgery:
•Anterior resection of rctosigmoid+primary
anastomosis,Peritonectomy,Multiple liver resections,
clearance of porta hepatus and caudate lobe, bilat.
Diaghramatic and pelvic stripping.
•EPIC with 5fu
•Smooth Post-OP course

93. 5th and 6th cases are doing fine as well.
Cases # 12 and 13, done two weeks back;
One of them is 72 yrs old female with high volume
disease(Ovarian)
-Cisplatinum HIPEC used.
No complication related to the HIPEC except ileus
for 7days.
Now ,in the ward , ready to be discharged.
2nd patient is peritoneal mesothelioma PCI >15
-Cisplatinum & Mitomycin C HIPEC used

96. THANK YOU