Here are the key steps: 1. The left subphrenic space is entered by incising the peritoneum overlying the left hemidiaphragm. 2. The peritoneum is dissected off the left hemidiaphragm in a cephalad direction towards the diaphragmatic crus. 3. The peritoneum is then stripped down the left paracolic gutter towards the pelvis, removing all peritoneal surfaces. 4. The left subphrenic peritonectomy is then completed, exposing the left hemidiaphragm and removing all peritoneal surfaces in the left subphrenic space.

1. CYTOREDUCTIVE
SURGERY AND HIPEC
DR AMIT DANGI
DEPARTMENT OF SURGICAL
GASTROENTEROLOGY
KGMU

2. OUTLINE
• PERITONEUM AS ORGAN
• CYTOREDUCTIVE SURGERY
• HIPEC AND ITS TECHNIQUES
• CRS + HIPEC IN CRC, MALIGNANT
MESOTHELIOMA, APPENDICIAL TUMORS,
PSEUDOMYXOMA, GASTRIC CANCER, OVARIAN
MALIGNANCY
• RESULTS/SURVIVAL
• INDIAN EXPERIENCE

5. EVOLUTION OF CRS AND HIPEC

7. WHY CRS AND HIPEC

8. WHY CRS AND HIPEC ???
• Dismal prognosis
• Median survival about 9 months.
• Now, long-term survival is possible in 25%–85% of patients
Canadian HIPEC Group. Curr Oncol, Vol. 22,
Chu DZ et al 1989
Sadeghi B et al 2000 (EVOCAPE 1 multicentre prospective study.)
Jayne DG et al; 2002.
Elias et al
Franko et al

10. • Natural history studies 
• Large proportion of patients develop isolated
peritoneal recurrence, and become cause of
death.
• These patients are appropriate for treatment
by CRS and HIPEC.
Segelman et al 2012
Yan D et al 2006
Dawson et al 1983

11. • Two essential components.
CYTOREDUCTIVE SURGERY (CRS).
– Removal of visible disease with peritonectomy
PERIOPERATICE
CHEMOTHERAPY(HIPEC/EPIC)
– Effective Concentation With Low Systemic Side
Effects.

17. PATIENT SELECTION
• Rule out the presence of distant extra abdominal
metastases.
• USG/ CT/ MRI/ FDG PET all useful,
• Standard is CT abdomen.
– sensitivity to detect Peritoneal cancer index (PCI), is
88% and
– accuracy 12%
– low sensitivity in assessing small-bowel lesions (8%–
17%), which further drop down in less than 5mm
lesion.
A. CYTO REDUCTIVE
SURGERY

18. Contra indications
• Extra abdominal metastasis
• Mesenteric Root Infiltration
• Massive Involvement Of Retroperitoneum
• Massively Infiltrated Pancreatic Capsule
• Expected Small Bowel Resection For More Than
One-third Of The Whole Length And
• Unresectable Liver Metastases Are Widely
Accepted Absolute Exclusion Criteria For Radical
CRS.

19. Absolute contraindications
• BIOPSY PROVEN EXTRA-ABDOMINAL DISEASE
LIKE LUNG METS, SCLN.
• EXTRAPERITONEAL DISEASE, SUCH AS
MORE THAN 3 LIVER METASTASES AND
N3 LYMPH NODES
UNKNOWN PRIMARY TUMOUR.
CANADIAN HIPEC GROUP GUIDELINES. Curr Oncol,
Vol. 22 , 2015

20. ABSOLUTE AND RELATIVE CRITERIA
FOR PATIENT SELECTION
CANADIAN HIPEC GROUP GUIDELINES. Curr Oncol,
Vol. 22 , 2015

21. RELATIVE CONTRAINDICATIONS :
• Bowel Obstruction at time of HIPEC
• Non responders to NACT (If Used To Downstage The Disease),
• Grade 3 Adeno- Carcinoma (Including Signet-ring Cells And Pmca)
• Frozen pelvis secondary to rectal cancer recurrence
SHORT INTERVAL B/W PRIMARY ADENOCARCINOMA & PC
(SYNCHRONOUS OR <6 MONTHS)
• Careful selection of patients
• NACT Is Strongly Recommended Before Crs Plus HIPEC
• Patients with up to 3 liver metastases responding to NACT could be
eligible if all other patient and disease criteria are favourable.
CANADIAN HIPEC GROUP GUIDELINES. Curr Oncol, Vol. 22 , 2015

22. DISEASE WORK UP
• AN APPROPRIATE HISTORY AND PHYSICAL EXAMINATION;
• APPROPRIATE BLOOD TESTS (CEA IN NON MUCINOUS DISEASE)
• TOTAL COLONOSCOPY
• CT IMAGING OF CHEST, ABDOMEN, AND PELVIS
• PET-CT : (IF AVAILABLE IN CASES OF NON- MUCINOUS DISEASE)
• CONFIRMATION OF DISEASE (THAT IS, PATHOLOGY REVIEW,
TISSUE BIOPSY, OR PROGRESSION ON IMAGING); AND
• OTHER APPROPRIATE EXAMINATIONS, INCLUDING LAPAROSCOPY.
Dromain C, et al. J Comput Assist Tomogr 2003;27:327–32.
Dromain C, et al. Staging of peritoneal carcinomatosis: enhanced ct vs. pet/ct. Abdom
Imaging 2008;33:87–93.

23. • 18F-FDGPET/CT and MRI No adv
• 18F-FDG PET/CT  between true relapses and
fibrotic scars caused by treatments is often
difficult.
• Not all histological types show good glucose uptake at 18F-
FDG PET/CT
•  showed that both CT and 18F-FDG PET/CT
were unable to give a correct staging of
carcinomatosis.
• No noninvasive procedure can correctly evaluate
PCI and expected cytoreduction index after
treatment, especially if the lesions are small.
Pfannemberg et al 2009 .
Passot G et al 2010

25. • Diagnostic imaging (CT and CT/PET) : First and
mandatory diagnostic test for peritoneal
carcinomatosis.
• When imaging-based PCI is in favor of enrolling the
patient for treatment, VLS staging allows assessment
of the true PCI, granting a correct selection of patients.
• 104/351 (29%) patients were excluded from surgical
exploration because of massive infiltration of the small
bowel or its mesentery basis detected by VLS.
• In a recent evaluation by Pasqual et al. preoperative CT
and FDG- PET/CT failed to detect PC in 9% and 17% of
cases
Valle et al
ROLE OF STAGING LAPAROSCOPY

27. LOCOREGIONAL STAGING
• A. JAPANESE CLASSIFICATION 1990
• A staging format for carcinomatosis from
gastric cancer was proposed:
» P1 (FEW NODULES ABOVE THE
MESOCOLON)  21% 2 YR OS
» P2 (MODERATE AMOUNT OF NODULES
EVEN BELOW TRANSVERSE
MESOCOLON)
» P3 (MANY SPREAD NODULES)  4% 2
YR OS

28. B. PRIOR SURGICAL SCORE
• PSS uses abdominopelvic regions 0-8 to create an important
quantitative prognostic indicator.
• No prior abdominopelvic surgery or biopsy : PSS of 0
• Up to 1 abdominopelvic region dissected : PSS of 1,
• 2 – 5 abdominopelvic regions : PSS of 2
• 6 or more regions dissected : PSS of 3.
• PSS of 3 or higher had a significantly reduced survival than
those patients with a PSS of 0, 1 or 2.
Look, M., Chang, D., Sugarbaker, P.H. 2003, Int. J. Gynecol. Cancer

29. C. GILLY’S CLASSIFICATION
Stage 0: no macroscopic signs of
disease
Stage I: nodules smaller than 5 mm,
confined to one abdominal region
Stage II: nodules smaller than 5 mm,
disseminated through the abdomen
Stage III: size of nodules between 5
mm and 2 cm
Stage IV: lesions larger than 2 cm

30. D. Dutch Simplified Peritoneal
Cancer Index (SPCI)
• Tumor is recorded as
Large >5cm
Moderate 1–5cm
Small <1cm
None
• Seven abdominal regions
I Pelvis
II Right lower abdomen
III Greater omentum,
transverse colon and spleen
IV Right subdiaphragmatic
area
V Left subdiaphragmatic area
VI Subhepatic and lesser
omental area
VII Small bowel and small
bowel mesentery
Disadvantage: Epigastric region not designated
ASCO Prog Proc 2002

31. E. Sugarbaker’s classification
-- PCI
In contrast to the PSS, the small bowel is assessed as an
additional 4 abdominopelvic regions, designated AR-9 to
AR-12 and includes the upper jejunum, lower jejunum,
upper ileum and lower ileum respectively.
The summation of the lesion size score in each of the 13
abdominopelvic regions is the peritoneal cancer index
(PCI), ranging from 0 to 39

33. A high score would suggest a minimal palliative
intervention.
Stage P1 to P2 of the Japanese classification
Gilly’s Stage I to II and to
Sugarbaker’s PCI of less than 13 (>20 is
relative C/I).

35. SURVIVAL

36. PROGNOSTIC FACTORS

38. Completeness of cytoreduction
(CC) score
• Major prognostic factor for survival in PC
patients.
• Absolute R0 resection is not necessary.
• According to this residual tumor classification,
– CC-0 no visible peritoneal seeding after CRS.
– CC-1 Persisting nodules less than 0.25 cm after CRS
indicates,
– CC-2 nodules between 0.25 and 2.5 cm indicates and
– CC-3 nodules greater than 2.5 cm indicates.
• The aim of CRS CC-0 and CC-1
Harmon RL
Sugarbaker PH

39. • If one has to consider CRS with HIPEC as a curative
treatment of PC, patients who cannot be classified as
expected CC0 should be excluded from the procedure.
• CC1 cases (residual lesions between 0.25 and 2.5 mm)
in HIPEC-responder patients can also be considered
CC0 after cytoreduction.
• In CC1 HIPEC nonresponders, CC2, and CC3, the
integrated treatment offers limited increase in OS but a
marked improvement in QOL; it can therefore be
considered as advanced palliative surgery.
Completeness of cytoreduction (CC)
score

41. Verwal Prognostic Score
• Prognostic score : 0.592C + 0.448D + 0.487H +
0.343 Re
C: 1 if CRC, 0 if not
R: 1 if CRC, 0 if not
D: 1 well/moderately well differentiated, 2 poor
H: 1 if no signet ring, 2 if there is signet ring
Re: Number of affected regions (1-7)

43. SURGICAL
CONSIDERATIONS
ASSESSMENT
PHASE
CYTOREDUCTIVE
PHASE
HIPEC
PHASE

44. Cytoreductive surgery is divided
into 3 phases:
• ASSESSMENT PHASE:
Rule out extraperitoneal disease (>3 liver mets or N3 LN)
To evaluate if a resection is feasible.
Measurement of PCI.
The decision to proceed—or not—is then made.
• CYTOREDUCTION PHASE:
Resection of all macroscopic disease
Evaluation of completeness of cytoreduction (cc)
• HIPEC Phase:
Delivery of HIPEC is performed, followed by creation of diverting
stomas (if required).
The abdomen is then closed..
Reconstructions are performed either before or after HIPEC.

45. ASSESSMENT PHASE
• In the case of a high PCI discovered at
laparotomy, or when a CC 0 resection is not
achievable, three subsequent strategies are
possible:

46. SITUATION 1
• Close the abdomen and consider NACT until
the best tumour response has been achieved
and then try again
• Encouraged in the case of grade 1 or 2 classical
adenocarcinoma, when a CC-0 resection
seems hard to achieve as demonstrated by the
assessment or when a very-high- risk resection
seems the only way to achieve CC-0.

47. SITUATION 2
• Proceed to a double cytoreduction with or
without systemic chemotherapy between the
procedures. This approach is used mainly in
the case of DPMA or PMCA-i with a PCI Score
exceeding 20.
• The goal of the first procedure is to remove all
tumour from the upper or the lower
abdomen; during the second procedure, the
goal is to remove all remaining tumour and to
proceed to the hipec phase.

48. SITUATION 3
• • Close the abdomen and consider best
supportive care if neoadjuvant systemic
chemotherapy is not an option.

49. • A decision to go ahead with the procedure
should be reserved for very motivated and
highly selected patients. The relevant
situations are
• DEFINITIVE END STOMA WITH CONCOMITANT
ILEAL BLADDER (PELVIC EXENTERATION),
• WHIPPLE PROCEDURE,
• SHORT-BOWEL SYNDROME, OR
• MAJOR HEPATECTOMY.

50. Peritonectomy procedures
The initially described six peritonectomy procedures have recently been modified.
SUGARBAKER 1995,1999, 2013

51. • Peritonectomy procedures should address
only macroscopic disease.
• Normal appearing peritoneal surfaces are not
stripped.
• Only structures or organs coated by disease
are resected.
Sugarbaker 2013

52. • Isolated tumor nodules are removed using
electro-evaporation using ball tip cautery
(viable tumor cells at margin)
• Electroevaporation/ electrosurgery
– Less blood loss,
– less dissemination
of tumor cells.
– High energy likely to
kill tumor cells at
resection margin

53. CYTO-REDUCTION IN 2
STEPS
• In selected cases of a high PCI score and DPAM OR PMCA-I,
performing the cytoreduction as two separate procedures
is an option if
• Complete Cytoreduction Is Expected To Last More Than 10–
15 Hours,
• If Blood Loss Is Too High, Or
• If Surgical Complications Make Proceeding With HIPEC a
Contraindication.
• In such a situation,
First Surgery : Infra-mesocolic area is addressed
Second surgery : Supra- mesocolic + HIPEC

54. CRS WITHOUT PERI-OPERATIVE
IPC

55. SURGICAL TECHNIQUES
• Vertical median xipho- pubic incision is
performed.
• The incision should always include the
umbilicus since, in cases of peritoneal
carcinomatosis, this anatomic site is at a very
high risk of cancer involvement.
• SELECTIVE AND RADICAL PERITONECTOMY

56. Locations of peritoneal surface
malignancy
• 3 IMPORTANT anatomic sites .
1. THE RECTOSIGMOID COLON : non-mobile, dependent
site and frequently layered by peritoneal metastases.
2. THE ILEOCECAL VALVE
3. ANTRUM OF THE STOMACH which is fixed to the
retroperitoneum at the pylorus.
• Tumor coming into the foramen of Winslow accumulates in
the subpyloric space and may cause GOO.
• Large volumes of tumor in the lesser omentum combined
with disease in the subpyloric space may require total
gastrectomy for complete cytoreduction
Carmignani CP, Sugarbaker TA, ET AL Cancer Metastasis
Rev 2003;22:465-72.
Sugarbaker PH. Eur J Surg Oncol 2002;28:443-6.

57. ABDOMINAL EXPOSURE
Elevation of the edges of the abdominal incision. Skin traction on
a self-retaining retractor facilitates dissection of abdominal wall
structures and minimizes the likelihood of damage to bowel loops
adherent to the abdominal wall.

58. Xiphoidectomy
Xiphoidectomy is used to gain maximal exposure
beneath the right and left hemidiaphragms

59. Total anterior parietal peritonectomy
Peritoneal window is necessary to assess the
need for total anterior parietal peritonectomy

60. Lateral dissection of the parietal peritoneum away
from the posterior rectus sheath and the
abdominal wall musculature completes the
anterior parietal peritonectomy.

61. Lysis of adhesions
• “Tumor cell entrapment hypothesis”
• All adhesions are separated, resected and
submitted as a pathological specimen.
• Cancer cells trapped within the scar tissue :
may not be eradicated by the perioperative
chemotherapy.

62. Self-retaining retractor provides
continuous exposure of all
quadrants of the abdomen
including the pelvis.

63. Left subphrenic peritonectomy

64. LEFT SUBPHRENIC
PERITONECTOMY COMPLETED

65. Greater omentectomy and
possible splenectomy
• To free the mid-abdomen of a large volume of
tumor, the greater omentectomy-splenectomy
is performed.
• Great care is taken not to traumatize the body
or tail of the pancreas

66. Right subphrenic peritonectomy
• Peritoneum is stripped from beneath the right
posterior rectus sheath to begin the
peritonectomy in the right upper quadrant of the
abdomen.
• Strong traction on the specimen
• Again, ball-tipped electrosurgery on pure cut is
used to dissect at the interface of tumor and
normal tissue.
• Coagulation current is used to divide the blood
vessels between diaphragm and peritoneum as
they are encountered and before they bleed.

67. Stripping of tumor from glisson’s
capsule
Electroevaporation of tumor from the liver surface with
resection of Glisson’s capsule

68. Completed right subphrenic
peritonectomy

69. Lesser omentectomy and
cholecystectomy with stripping
of the hepatoduodenal ligament

70. Circumferential resection of the
hepatogastric ligament and
lesser omental fat by digital
dissection

71. Stripping of the omental bursa
after dividing the peritoneal
reflection between left caudate
lobe and superior vena cava

72. Stripping of peritoneum from the
floor of the omental bursa and
body of the pancreas has been

73. A. Division of the pont hepatique (hepatic bridge) for
cytoreduction along the umbilical ligament AND
B. Pont hepatique (hepatic bridge) divided showing
tumor nodules on the umbilical ligament beneath the
divided liver parenchyma. The umbilical ligament will
be resected at its entrance into the liver parenchyma.

74. The complete pelvic
peritonectomy includes uterus
and ovaries, rectosigmoid colon
and pelvic peritoneum.

75. Resection of rectosigmoid colon and
cul-de-sac of Douglas.

76. Vaginal closure and low
colorectal anastomosis

77. Left colon mobilization for a
tension-free low colorectal
anastomosis

78. Optimization of cytoreduction of
small bowel and its mesentery
ELECTROSURGICAL DESTRUCTION
(ELECTROEVAPORATION) OF TUMOR
NODULES ON SMALL BOWEL
MESENTERY DURING HYPERTHERMIC
INTRAPERITONEAL CHEMOTHERAPY
USING THE OPEN TECHNIQUE.

79. CYTOREDUCTION OF SMALL
BOWEL AND ITS MESENTERY
Type 1 - non-invasive tumor nodules are usually
resectable using a curved Mayo scissor.

81. Techniques & procedure
Radicality of the Peritonectomy Procedure
• Depends upon histology of primary tumor & pattern
of spread in peritoneal cavity
• Aggressive complete peritonectomy reserved for
– Generalized peritoneal carcinomatosis
– Pseudomyxoma peritonei
– Appendix cancer ( Cystoadenocarcinoma G1, G2, G30
– Colorectal cancer ( Mucinous G1, G2, G3)
– Diffuse malignant mesothelioma
– Ovarian cancer (Mucinous)

82. Techniques & procedure
Ostomy ?
• 13 studies mentioned about stoma
• In most studies bowel complications same in
spite of stoma
• If rectum excised
– Perform diversion
• If rectum spared
– Can avoid stoma
J Surg Oncol 2004
Eur J Surg Oncol 2006
Surg Oncol Clin N Am 2003

84. Timing of Bowel
Anastomoses
• Before HIPEC
Advantages
1. Reduce costs and
operation time
Disadvantages
1. Mechanical traction
during perfusion can
impair integrity of
anastomoses
• After HIPEC
Advantages
1. Effect of heat &
chemotherapy on suture
healing
2. Possibility to treat
bowel margins against
eventual implantation of
tumor cells
Disadvantages
1. Bowel edema so
Technically more difficult.

85. HIPEC

87. THE FIRST HIPEC

90. B. Peri operative intra peritoneal
Chemotherpy
NIPS
HIPEC
EPIC : First 4 or 5 days after surgery in
normothermic conditions (EPIC)
Or Combination of both or all.
• Term HIPEC coined by the group from the
Netherlands Cancer Institute.
Gonza´lez-Moreno S. Peritoneal surface oncology: 2006

91. Why HEAT ????
• Hyperthermia.
• Exhibits a selective cell-killing effect to malignant cells
• potentiates the cytotoxic effect of chemotherapy
agents,
• Enhances the tissue penetration of the administered
drug.
Sticca RP, Dach BW. Rationale for hyperthermia with
intraoperative intraperitoneal chemotherapy agents.
Surg Oncol Clin N Am 2003;12:689–701.

92. VARIABLES
• Chemotherapy agents
• Duration of HIPEC
• Level of heat for hyperthermia
• Different techniques for abdominal irrigation
• Laparoscopic HIPEC in selected patients.

93. Proper selection of chemotherapy
agents for HIPEC
THE HEAT-AUGMENTED DRUGS WITH THE MOST
FAVORABLE AUC RATIOS ARE
MITOMYCIN C
DOXORUBICIN,
GEMCITABINE, AND
PEGYLATED-LIPOSOMAL DOXORUBICIN.
HEAT-AUGMENTED DRUGS WHICH HAVE A
PROLONGED RETENTION ARE
GEMCITABINE AND
PEGYLATED- LIPOSOMAL DOXORUBICIN.

94. • Acute phase drugs
• Heat augmented (MITOMYCIN C, DOXORUBICIN, GEMCITABINE,
AND PEGYLATED-LIPOSOMAL DOXORUBICIN).
• High AUC
• Prolonged retention and slow clearance (GEMCITABINE
AND PEGYLATED- LIPOSOMAL DOXORUBICIN)
• Continous infusion of drug (ifosfamide)
• Repeated dosing of the chemotherapy agents.
Sugarbaker. J Gastrointest Oncol 2016;7(1):29-4

95. PRODIGE 7 : FRENCH TRIAL

96. Between HIPEC/EPIC
• NO Randomized controlled studies.
• HIPEC alone VS HIPEC followed by EPIC or EPIC
alone,
↓ LESS MORBIDITY IN HIPEC (FISTULA
FORMATION)
EQUAL SURVIVAL.
Elias D et al 2007
• Survival advantage of HIPEC over EPIC
Glehen et al 2003

97. Rationale of HIPEC
• The intraperitoneal route, when properly
used, will
– allow uniform distribution by surgeon/ positional
changes
– high concentration of anticancer therapy at the
site of the malignancy, when disease load is
minimal
– Prevent TUMOR CELL ENTRAPMENT

98. • Currently, protocols exist attempting to use HIPEC to reduce
or eradicate local- regional failures in those patients who
are at risk for subsequent local failure and/or peritoneal
metastases.
• The COLOPEC trial is currently active in the Netherlands
and
• the PROMENADE protocol is in the process of being
activated from Rome, Italy.
Adjuvant HIPEC in High Risk Colon Cancer (COLOPEC). Available online: https://clinicaltrials.gov/ ct2/show/NCT02231086
Sammartino P, Societa Italiana di Chirurgia Oncologica (SICO).
PROMENADE Trial (PROactive Management of ENdoperitoneal spreAD in colonic cancer).2015.

99. Complications
• Over all complication rates : 30-45%
• Chemotherapy toxicity to kidneys, bone marrow,
liver, lungs- 2-5%
• Organ damage secondary to hyperthermia
(Careful intra-operative monitoring avoids them)
• Surgical complications – 25-30%
– MC small bowel fistula
• Mortaility during procedure- 0-5%
EJSO 2008

100. TWO MAIN METHODS
1. OPEN ABDOMEN TECHNIQUE
2. CLOSED ABDOMEN TECHNIQUE.
3. MIXED METHODS (SEMIOPEN OR
SEMICLOSED) HAVE BEEN REPORTED.

101. OPEN
METHOD OF
HIPEC

102. CLOSED METHOD OF HIPEC

103. CREDITS AND DEBITS OF TWO DIFFERENT TECHNOLOGIES FOR
HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY

104. “PERITONEAL CAVITY
EXPANDER” (PCE)
• Variation of the open technique
• Acrylic cylinder containing inflow
& outflow lines, secured over
laparotomy wound
• Rarely been used outside Japan.
Fujimura and colleagues and Yonemura and colleagues

105. PERITONEAL CARCINOMATOSIS FROM
COLORECTAL ORIGIN

110. PROGNOSTIC FACTORS

111. • 47 studies including 4 comparative studies and
43 observational studies of CRS with PIC
• Significant survival advantage with HIPEC (P <
0.0001).
• No advantage of EPIC only.
• Combined liver and PC should not be excluded
from resection if feasible

113. Two main approaches to HIPEC in colorectal PC
1. THE USE OF MITOMYCIN C FOR 60-90 MIN AT 41 ℃
2. OXALIPLATIN FOR 30 MIN AT 43 ℃.

114. PREVENTIVE ROLE OF CRS
HIPEC
Sugarbaker PH. Second-look surgery for colorectal cancer: revised selection factors and
new treatment options for greater success. Int J Surg Oncol 2011;2011:915078.

119. Role of second look surgery

120. Future Trials
• Several randomized trials :
PROPHYLOCHIP
GASTRICHIP
PROMENADE
explore the strategy of surgery plus HIPEC in
high risk patients

121. The median survival : 13 to 29 months, and
5-year survival rates ranged from 11% to 19%.
CC-0 : benefited most, with
median survival varying from 28 to 60 months and
5-year survival ranging from 22% to 49%.

122. Diffuse malignant peritoneal
mesothelioma (DMPM)
• Rare disease.
• Progressive peritoneal seeding
• Ascites, abdominal pain, and asthenia
• CT : Ascites, peritoneal thickening,
abdominal mass, and mesenteric
thickening.
• Median survival of about 1 year

123. • Cisplatin and pemetrexed.
• 2nd line  vinorelbine and gemcitabine +/-
platinum compounds.
• CRS and HIPEC  Median survival grew from
12 months with a systemic chemotherapy
treatment to 53 months with CRS with HIPEC,
with 50% 5-year overall survival.
Deraco M, et al. J Surg Oncol 2008]

126. PERITONEAL CARCINOMATOSIS FROM
APPENDICEAL/PMP ORIGIN
• Basingstoke group in 1987 first described CRS +
IPCT in PC from appendicial origin.
• 3 types
 DISSEMINATED PERITONEAL ADENOMUCINOSIS
(DPAM)
 PERITONEAL MUCINOUS CARCINOMATOSIS (PMCA)
 PMCA WITH INTERMEDIATE OR DISCORDANT
FEATURES(PMCA I/D).
Ronnett et al

127. WAKE FOREST CLASSIFICATION
(NEW CLASSIFICATION OF PC)
• LOW-GRADE
MUCINOUS
CARCINOMA
PERITONEI
•  62% 5 YR OS.
• DPAM,  36 % 10 yr OS
• PMCA I/D.  28 % 10 yr
OS
• well differentiated
mucinous carcinomatosis
and
• HIGH GRADE
MUCINOUS
CARCINOMA
PERITONEI
•  37% 5 YR OS.
• moderately or poorly
differentiated
adenocarcinomas,
• cases with signet-ring cell
component
• PMCA  3% 10 yr OS.

128. SELECTION CRITERIA BASED ON THE
GRADE OF THE APPENDICEAL PRIMARY.
• LOW-GRADE APPENDICEAL
CANCER
CRS attempted regardless of
the volume of disease.
Patients with voluminous liquid
ascites/ CC-0 CRS  HIPEC.
In patients without
symptomatic ascites but with
excessive post-CRS residual
disease the perfusion is
aborted.
• HIGH-GRADE / NON-
MUCINOUS APPENDICEAL
CA
• IF CC-0 not possible : Not
taken for cytoreduction
• Systemic chemotherapy
followed by restaging
imaging to evaluate for
resectability.

129. PROGNOSTIC FACTORS
1. HISTOPATHOLOGICAL TYPE
2. COMPLETE CRS
3. TUMOR MARKERS
• Complete cytoreduction is the standard of care in PMP.
• ? Role of HIPEC is under trial.
To date, there is no published prospective
randomized trial comparing CRS with CRS/HIPEC
(although several trials have been attempted).
• ? Extent of peritonectomy
Unlike other gastrointestinal primaries of PC, resection
of all peritoneal surfaces is highly recommended.

131. PERITONEAL CARCINOMATOSIS FROM
GASTRIC ORIGIN
• Despite initial R0 resection, peritoneal metastasis
develops in 60% of cases with T3 and T4 tumors.
• 10% to 20% of patients with gastric cancer have
peritoneal deposits at presentation.
• OS  5-6 months with morbidity.
• Therefore, role of CRS HIPEC should be
considered.
•  Therapeutic
•  Preventive

132. Treatment-related mortality was 3.9%,
major complications occurred in 23.6%
The median survival rate was 15.8 months,
with 1-, 2-, and 5-year survival rates of 66%, 32% and 10.7%,
respectively

134. PERITONEAL CARCINOMATOSIS FROM SMALL BOWEL
ORIGIN
• Rare disease
• Grave prognosis (median OS 9 to 20 months)
• 25% of the patients have synchronous PC  OS
3.1 mo with palliative tt.
Sadeghi et al
• Chua et al (retrospective trial)reported median
disease free and overall survival rates of 12 mo
and 25 mo in 7 patients who underwent
complete CRS and HIPEC or early postoperative
intraperitoneal chemotherapy.

136. • In multivariate analysis, OS was influenced by
CC SCORE
TYPE OF CHEMO PERFUSION DRUG
NODAL STATUS
TUMOR GRADE.
• In a Cox regression model, independent
predictors of overall survival
CC SCORE
TUMOR GRADE
Ceelen and coworkers
PREDICTOR OF OS

137. Divided treatment into time points:
FRONT-LINE,
FRONTLINE FAILURE (PERSISTENT DISEASE AT THE
END OF FRONT-LINE TREATMENT),
CONSOLIDATION(MAINTENANCE TREATMENT)
RECURRENT DISEASE.

138. Frontline therpay
• Combination of CRS and chemotherapy.
The median OS for patients:
– Combination IV/IP chemotherapy : 65.6 months
– CRS WITH IV CT ONLY: 49.7 months
Gynecologic Oncology Group (GOG) study 172/ 104/ 114

139. IP chemotherpy
• A Cochrane Collaboration meta-analysis of all
randomized studies using IP therapy for EOC
(Epithelial ovarian tumors)  significant
survival advantage for IP delivery.
–  optimal regimen for IP chemotherapy ?
–  adding HIPEC

140. FL Failure
• A study of CRS and HIPEC in this setting was
instituted by surgeons at the Instituto Tumori
in Milano but closed early because of
excessive morbidity and poor study accrual.

141. Consolidation
• Multiple trials of maintenance (consolidation) therapy,
there is still no proven method.
» continuation of systemic chemotherapy beyond 6 cycles,
» use of intraperitoneal therapy, and
» experimental treatments including immunotherapy.
• No RCTs investigating HIPEC for consolidation, but
those that have been performed suggest that HIPEC
may have beneficial effects in this situation.
• Few retrospective studies
(Bae JH & Gori J)

142. RECURRENT
In the HYPERO report, despite 85% of the women treated for recurrence having

143. • Long term results of HYPERO (Helm et al ) awaited.
• 3 large, ongoing, randomized studies investigating
HIPEC based in 3 different European countries.
• Netherlands Cancer Center
– Role of HIPEC after NAC (at interval debulking).
• French CHIPOR study.
– patients with platinum-sensitive recurrent disease
receive chemotherapy with carboplatin and liposomal
doxorubicin or paclitaxel and then undergo CRS.
– CC-0/CC-1 : Randomized to HIPEC with cisplatin 75 mg/m2
versus no HIPEC
• Italian HORSE,
– patients with platinum-sensitive recurrence will be
randomized to CRS with HIPEC with cisplatin 75 mg/m2
versus CRS alone.

144. Sarcomatosis
• High loco-regional recurrence/relapse
• Conventional therapy : 2 year survival in
patients with local-regional disease
progression or sarcomatosis.
• CRS + HIPEC  5-year OS >30%.
• Large benefits in pts with Uterine
Sarcomatosis.

145. Laparoscopic HIPEC
• Four studies
– Used in patients with malignant ascites in view of
palliation
Valle et al. in 52 patients with refractory malignant ascites
observed one clinical recurrence of the ascites after
laparoscopic HIPEC
Less invasive
Limited experience.

146. STUDIES ON COMBINED LAPAROSCOPIC
CYTOREDUCTIVE SURGERY AND HIPEC

148. Characteristics of patients undergoing
CRS and HIPEC

149. Operative findings in 384 patients
treated with CRS and HIPEC

150. Morbidity and Mortality in patients
undergoing CRS and HIPEC

152. Sugarbaker 2015

153. Current indications for cytoreductive surgery and
perioperative intraperitoneal chemotherapy
Sugarbaker 2015