Peritoneal carcinomatosis treatment CRS HIPEC

1. Peritoneal Carcinomatosis
Dr Dharma Poonia
Rajiv Gandhi cancer institute,
NEW DELHI.

2. • Introduction & Natural history.
• Patient selection
• CRS
• HIPEC
• Role in different diseases
• Summary

3. • Peritoneal carcinomatosis (GI and ovarian),
mesothelioma, and sarcomatosis are included in
the group of diseases collectively referred to, as
peritoneal metastases.
• Dismal prognosis of patients with PC with BSC/CT.
– 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

4. • 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

5. • Emerging technology
» Sugarbaker 1989
– it is a loco regional disease but not a metastatic process, can
be taken curative intent.
• Two essential components.
Cytoreductive surgery (CRS).
– Removal of visible disease with peritonectomy
Periop chemotherapy(HIPEC/EPIC)
– effective concerntation with low systemic side effects.

6. Patient selection
• Rule out the presence of distant metastases in
extra abdominal areas, which is an absolute
criterion of exclusion.
• 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

7. • 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.

8. • 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 that 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

10. • Diagnostic imaging (CT and CT/PET) is still considered
the 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.
» Valle et al
ROLE OF STAGING LAPAROSCOPY

11. • Difficulty of trocar positioning in the presence
of abdominal wall tumor masses or adhesions
from previous surgery
• Reliability and efficacy of the procedure in
evaluation of complete staging
• Contamination of the port sites.

12. 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
• With slight modifications, can be used even for
different forms of carcinomatosis.
• not accurately describe the distribution and
localization of neoplastic lesions

13. B. 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
• Even so, this classification is not detailed
enough about the distribution of the lesions

14. 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 ASCO Prog Proc 2002
Disadvantage: Epigastric region not designated

15. Sugarbaker’s classification -- PCI
• Location
• Lesion size
• The abdomen is divided into 9 sectors and small bowel
into into 4 more parts.
• for each sector a score is assigned (Lesion Size score
[LS]) related to the actual disease:
» LS 0: no macroscopic evidence
» LS 1: maximum diameter of the lesions up to 0.5 cm
» LS 2: maximum diameter up to 5 cm
» LS 3: maximum diameter larger than 5 cm or confluent nodules
• The total of the scores for all sectors gives the PCI.
Stage P1 to P2 of the Japanese classification
Gilly’s Stage I to II and to
Sugarbaker’s PCI of less than 13.

17. Prognostic factors
• Histopathology,
• the peritoneal cancer index (PCI),
• the completeness of cytoreduction score (CC),
• TNM (tumor, node, metastasis) stage with
peritoneal cytology play a central role in
patient selection.

18. 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

19. • If one has to consider Peritonectomy with HIPEC as a
curative treatment of peritoneal carcinomatosis,
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 quality of life; it can therefore
be considered as advanced palliative surgery.
Completeness of cytoreduction (CC)
score

20. Peritonectomy procedures
• The initially described six peritonectomy procedures have
recently been modified to the:
» 1) epigastric peritonectomy,
» 2) right subdiaphragmatic peritonectomy,
» 3)) left subdiaphragmatic peritonectomy,
» 4) greater omentectomy + splenectomy
» 5) lesser omentectomy,
» 6) pelvic peritonectomy,
» 7) cholecystectomy and resection of the omental bursa,
» 8) right parietal peritonectomy,
» 9) left parietal peritonectomy, and
» 10) resection of other organs (antrectomy, colectomy other than low
anterior, subtotal colectomy, total gastrectomy, segmental intestinal
resection)
» (Sugarbaker, 1999).
» (Sugarbaker, 1995).

21. • Peritonectomy procedures should aim address
macroscopic disease.
• Isolated tumor nodules are removed using
electroevaporation (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

22. • CRS in the absence of perioperative
intraperitoneal chemotherapy may actually
harm patients in the long run rather than help
them.
• It will cause free viable tumor cells that can
implants in deeper layers of abdomen, near
vital organs/ structure and leads to
complications.

23. Peritoneal stripping from beneath the left hemidiaphragm (left upper
quadrant).
From Sugarbaker

24. Right upper quadrant peritonectomy
From Sugarbaker

25. Cholecystectomy, lesser omentectomy and stripping of the
omental bursa
From Sugarbaker PH: Peritonectomy procedures

26. Initiation of the pelvic peritonectomy by
defining the limits of the dissection.

27. In patients who require gastrectomy in
addition to extensive cytoreduction, a high
diverting jejunostomy is performed. This
ostomy is closed in approximately six
months with a second-look surgery. (From
Sugarbaker PH:

28. 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)

29. 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

30. 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.

31. B. Peri operatice Chemotherpy
– HIPEC
– EPIC in the first 4 or 5 days after surgery in
normothermic conditions (EPIC), or as a
– combination of both.
•  Intraperitoneal
•  Hypethermia
• First described in 1978 by Dedrick et al
• result in a higher drug concentration and longer half-life in
the peritoneal cavity, as compared with intravenous (IV)
administration.

32. • Term HIPEC coined by the group from the
Netherlands Cancer Institute.
» Gonza´lez-Moreno S. Peritoneal surface oncology: 2006
•  Hyperthermia.
• It self 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.

33. true efficacy of HIPEC alone in
eradicating the residual nonvisible disease
after CCRS, applying the usual HIPEC
Procedure
2012

34. Between HIPEC/EPIC
• Randomized controlled studies have not been performed to
formally assess which modality of PIC is more
advantageous.
• A few retrospective comparative studies are available
showing a trend for or even an advantage for HIPEC alone
over HIPEC followed by EPICor EPICalone, in terms of
morbidity (fistula formation), although not in terms of
survival.
» Elias D et al 2007
• A recent small retrospective case-control Swedish study
reports a survival advantage of HIPEC over sequential
postoperative intraperitoneal chemotherapy after
complete cytoreduction in colorectal carcinomatosis.
» Glehen et al 2003

35. 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

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

37. • Two main methods
• open abdomen technique and
• closed abdomen technique.
• mixed methods (semiopen or semiclosed)
have been reported.

38. Open method
of HIPEC

39. Closed method of HIPEC

40. “peritoneal cavity
expander” (PCE).
• A variation of the open technique described.
• The PCE is an acrylic cylinder containing inflow
and outflow lines that is secured over the
laparotomy wound
• The use of the PCE is very limited (if any) at the
present time and has rarely been used outside
Japan.
» Fujimura and colleagues and Yonemura and colleagues

41. • Each HIPEC method has its own advantage
and disadvantages.
• No formal prospective controlled comparison
regarding patient outcomes, morbidity, or
surgical staff safety.
• A call for future studies to definitively answer
this question was made but has not been
answered.
• Consensus statement by panel of experts in Milan
2006

43. PERITONEAL CARCINOMATOSIS FROM
APPENDICEAL/PMP ORIGIN
• Treatment of PC from appendiceal origin with
CRS and intraperitoneal CT was first described
by the Basingstoke group in 1987
• There are three widely accepted types of PMP
– Disseminated peritoneal adenomucinosis (DPAM),
– peritoneal mucinous carcinomatosis (PMCA) and
– PMCA with intermediate or discordant
features(PMCA I/D).
» Ronnett et al

44. • According to Wake Forest Classification(new
classification of PC ) cases
• low-grade mucinous carcinoma peritonei  62%
5 yr OS.
• DPAM,  68 % 10 yr OS
• PMCA I/D.  28 % 10 yr OS
• well differentiated mucinous carcinomatosis and
• low-grade mucinous appendiceal neoplasms
• High grade mucinous carcinoma peritonei 
3&% 5 yr OS.
• moderately or poorly differentiated adenocarcinomas,
• cases with signet-ring cell component
• PMCA  3% 10 yr OS.

45. • Selection criteria based on the grade of the
appendiceal primary.
• For low-grade appendiceal cancer a cytoreduction is
attempted regardless of the volume of disease.
• HIPEC after incomplete cytoreduction depends on the
volume of residual disease and the amount of ascites.
– Patients with voluminous liquid ascites/ CC zero CRS 
HIPEC.
– In patients without symptomatic ascites but with excessive
post-CRS residual disease the perfusion is aborted.

46. • High-grade / nonmucinous appendiceal Ca
• Patients with imaging of disease not amenable
to complete cytoreduction are not taken into
the operating room.
• These patients are treated with systemic
chemotherapy followed by restaging imaging
to evaluate for resectability.

47. • Prognostic factors for PC from appendiceal origin are
– histopathological type,
– complete CRS and
– 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.
– however this issue is controversial due to the lack of
randomized trials comparing limited and complete
peritonectomy in PMP.

48. PERITONEAL CARCINOMATOSIS FROM
GASTRIC ORIGIN
• After local lymph node metastasis, peritoneal seeding
is the most common site for tumor deposits in gastric
cancer.
• 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 is should be considered.
•  Therapeutic
•  Preventive

49. 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

50. Gastric cancer

51. • In 2011, Yang et al performed the first prospective
randomized phase Ⅲ clinical trial on CRS and HIPEC in
68 patients(34+34) with PC from gastric cancer.
• Median survival was significantly better in the CRS and
HIPEC group than the CRS only group (11 mo vs 6.5
mo).
• A review of 10 studies including 441 patients who
underwent CRS and HIPEC for gastric PC reported an
overall median survival of 7 mo which was improved to
15 mo when complete CRS was achieved.

52. • Prognostic factors
– Completeness of
cytoreduction and
– Presence of ascites.
Glehen et al 2010
n 159, retrospective review

53. • Eligibility for HIPEC can be determined with
laparoscopic staging in patients with PC and
peritoneal lavage in advanced gastric cancer
• Further RCTs need to establish the role.
• Currently, Rau and colleagues in Germany are
conducting a phase 3 trial, the GASTRIPEC
study

54. Prevention of Gastric Cancer
Peritoneal Metastases
• Few Korean and Japanese phase 3 trials, shown
benefits of HIPEC in an adjuvant setting (T3, T4
and LN+ disease),.
• Yan and coworkers in a meta-analysis
• However, increased risk of intra-abdominal
abscess and neutropenia were also
demonstrated.
• Currently, a prospective randomized trial is being
performed in France to test adjuvant HIPEC in
gastric cancer.

55. PERITONEAL CARCINOMATOSIS FROM SMALL BOWEL
ORIGIN
• Rare disease with grave prognosis (median OS 9
to 20 mo)
• Approximately 25% of the patients present with
synchronous PC  OS 3.1 mo with palliative tt.
» Sadeghi et al[6].
• 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.

56. – signet-cell morphology,
– lymphovascular invasion and
– poor differentiation had worse oncologic outcomes,
– where lymph node metastasis did not influence survival.
• Marchettini et al and Jacks et al
• showed improved median survival with CRS and intraperitoneal
chemotherapy (12 mo and 30.1 mo, respectively).
• Complete CRS and HIPEC can be an option for selected
patients.
• however large series and randomized trials are needed.

57. PERITONEAL CARCINOMATOSIS FROM
COLORECTAL ORIGIN
• Patients with colorectal cancer present with PC in
approximately 10% of all cases.
» Glehen O et al 2003
• 40% patients of CRC devlop peritoneal only recurrence
[39].
» Cintron JR et al
• Half of those are synchronous PC with advanced stage
of the primary tumor and the median survival rate with
palliative management is very poor.
» Sadeghi B et al 2004
– Therapeutic
– Preventive

58. • The first randomized trial on CRS and HIPEC revealed a 2-
times shorter median survival (12.6 mo) in patients with
systemic CT alone than in the CRS and HIPEC (20 mo)group
(P = 0.03) n- 105
» Verwaal et al 2003 (amsterdam group),
• The median progression-free survival was 7.7 months in the
control arm and 12.6 months in the HIPEC arm (P = 0.020).
• The median disease-specific survival was 12.6 months in
the control arm and 22.2 months in the HIPEC arm (P =
0.028
» verwaal et al 2008 (8 year FU))
» Modern CT agents have prolonged median survival up to 19 mo in
patients with synchronous colorectal PC; however the results of
systemic CT alone is still poorer than CRS and HIPEC treatment.
• Saltz et al 2008
• Klever et al 2010

59. • A French multicenter study, including 523 patients,
• revealed that patients who were not amenable to
complete cytoreduction have similar median survival (9
mo) with systemic CT alone.
• However median survival was 30 months in optimally
treated patients
• Completeness of cytoreduction and PCI scores are
quantitative prognostic indicators of long-term results
» )
Elias et al 2010 (french study), JCO

60. • 47 studies included including 4 comparative
studies and 43 observational studies of CRS with
PIC
• Significant advantage with HIPEC (P < 0.0001).
• No advantage of EPIC only.
• Combined liver and PC should not be excluded
from resection if feasible
• However, there is a need for further evaluation of
the prognostic significance of lymph node and
liver involvement, ideally in large prospective
trials

62. • An absolute contraindication for complete
cytoreductive surgery (CCRS) plus HIPEC is a
– poor general status,
– the presence of extraperitoneal metastases, and a
– huge and diffuse PC. (PCI more than 20.)
• Relative contraindications are a
– subocclusive syndrome caused by more than 1 digestive
stenosis,
– Peritoneal disease progressing under chemotherapy, and
– the presence of more than 3 resectable liver metastases
(liver metastases are not contraindicated provided there
are fewer than 4 and if they are easily resectable )
» Elias D 2006

63. • Currently, there are two main approaches to
HIPEC in colorectal PC:
• The use of mytomycin C for 60-90 min at 41 ℃ and
• oxaliplatin for 30 min at 43 ℃.
• In the literature results on survival and
morbidity in HIPEC series for the two agents
are comparable.

66. Preventive role of CRS HIPEC
• Early diagnosis of peritoneal metastases is not
possible with radiologic imaging, but only with
a laparotomy,
• This is why the authors proposed second-look
surgery plus HIPEC in asymptomatic high risk
patients patients ( resected limited peritoneal
disease, ovarian deposit, perforated primary).
» Elias et al
» Sugarbaker

67. • N- 47 , high risk patients
• Second look laparotomy , Who not shown
peritoneal disease
• HIPEC vs Nothing
• The subgroup receiving HIPEC developed far
fewer peritoneal recurrences than those who
had not received HIPEC (17% vs 43%,
respectively) (p= 0.02).
» Elias et al (French trial )

68. Role of second look surgery

69. • Patients without established peritoneal disease
but at high risk for subsequent peritoneal
progression are being treated with HIPEC during
the same procedure used to resect the primary
tumor
– In case of recurrence the PCI will be maximally low.
– reliable radiologic tests to detect the progression of a
low volume of peritoneal metastases do not exist.
– Obviate the need of a second-look surgery.
» Verwaal 2004
» Elais d 2006

70. PERITONEAL CARCINOMATOSIS FROM
OVARIAN ORIGIN
• Ovarian cancer is a peritoneal surface
malignancy that remains within the peritoneal
cavity for much of its life history.
• Recurrence is common, with 70% of cases
having peritoneal disease, mostly peritoneal
only.

71. • Predictor of OS.
• In multivariate analysis, overall survival was influenced
by
– completeness of cytoreduction,
– type of chemo perfusion drug,
– nodal status, and
– tumor grade.
• In a Cox regression model, independent predictors of
overall survival
– Completeness of cytoreduction and
– tumor grade
» Ceelen and coworkers

72. • Divided treatment into time points:
– Front-line,
– Frontline failure (persistent disease at the end of
front-line treatment),
– Consolidation(maintenance treatment)
– Recurrent disease.

73. Frontline therpay
• Standard front-line treatment of EOC involves the
combination of cyto reductive surgery (CRS) and
chemotherapy.
• Gynecologic Oncology Group (GOG) study 172/
104/ 114
– The median OS for patients treated with combination
IV/IP chemotherapy was 65.6 months versus 49.7
months for patients treated with CRS and IV
chemotherapy only.
– Due to high toxicity only 42% patients able to
complete chemotherapy, so ..

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

75. here are no RCTs and the studies are heterogeneous

76. • United States, the Hyperthermic Intraperitoneal
Chemotherapy in Ovarian Cancer Registry
(HYPERO) Helm et al
• n- 26 patients (front line), treated with CRS and
HIPEC who fitted entry criteria for GOG 172,
having residual disease of less than 1 cm.
• There was no significant difference in the OS
(HIPEC 57.5 months, GOG 172 65.6 months, and
2-year OS 66.4%: 82%) and 2-year PFS (47.6%:
53%).

77. 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.

78. 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.
• There have been no randomized studies
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)

79. • Initial stage III EOC.
• 68 underwent Second-look laparotomy
following completion of front-line therapy:
• All received further IV chemotherapy
following the HIPEC (carboplati 5 30,
paclitaxel)
• The 3 year PFS was 56.3%and
16.7%respectively (P 5 .00028) and the 5-year
OS was 66.1%and 31.3% (P 5 .0003).
Bae JH 2007

80. • There may be a problem with using oxaliplatin
for consolidation.
• One of 2 recent studies reported a high
frequency of bleeding after surgery leading to
early closure.
• ? What should be target population.
• ? No RCTs.

81. Recurrent
Despite the large numbers, the studies are difficult to compare and interpret
because of their heterogeneity.
In the HYPERO report, despite 85% of the women treated for recurrence having
PC and 29% being platinum resistant, the median OS was 23.5 months

83. • Despite the extensive use of HIPEC for EOC
since the first report in 1994, there is no
defined conclusion regarding its use in ca
ovary.
• PRCTs and registry based reporting
encouraged.

84. • 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 debluking).
• French CHIPOR study.
– patients with platinum-sensitive recurrent disease receive
chemotherapy with carboplatin and liposomal doxorubicin or
paclitaxel and then undergo CRS.
– Those whose disease is resected to no visible disease or no greater
than 2.5 mm residual are randomized to HIPEC with cisplatin 75
mg/m2 versus no HIPEC
• In the Italian HORSE,
– patients with platinum-sensitive recurrence will be randomized to CRS
with HIPEC with cisplatin 75 mg/m2 versus CRS alone.

86. Diffuse malignant peritoneal
mesothelioma (DMPM)
• Rare disease.
• It progressive peritoneal seeding, eventually
leading to the patient’s death due to tumor
layering on peritoneal surfaces, bowel
obstruction, and intractable malignant
ascites.
• Ascites, abdominal pain, and asthenia were
the most frequent symptoms present on
77%, 69%, and 43% of patients.
• CT scan shows ascites, peritoneal
thickening, abdominal mass, and
mesenteric thickening,

87. • Cisplatin and pemetrexed.
• 2nd line  vinorelbine and gemcitabine, either
alone or combined with platinum compounds.
• Traditional therapy with palliative surgery and
systemic or intraperitoneal chemotherapy is
associated with a median survival of about 1
year, ranging from 9 to 15 months.
• 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, Bartlett D, Kusamura S, et al. Consensus statement on peritoneal
mesothelioma. J Surg Oncol 2008;98:268–272. [PMID: 18726890]

89. Sarcomatosis
• Soft tissue tumors of the viscera or
retroperitoneum are associated with high
rates of local-regional relapse.
• During surgical resection , cancer cell seedling
happens/ narrow margin  local-regional
recurrence.
• In patients with local-regional disease
progression or sarcomatosis, the survival is
limited to approximately 2 years.

90. • CRS + HIPEC  an overall 5-year survival was
>30%.
• Unusually large benefits with CRS and HIPEC in
patients with uterine sarcomatosis have been
reported.
• The mechanical removal of sarcoma
peritoneal metastases that occurs with HIPEC
may be as important or even more important
than the cytotoxic effects.

91. Laparoscopic HIPEC
• Four studies
– Used in patients with malignant ascites in view of
palliation
– No peritonectomy done in these cases
– Available studies on 5-14 patients
– Advantages
• less invasive
– Disadvantages
• Cellulits
• Experience