Peritoneal Carcinomatosis

Dr Dharma PooniaRajiv Gandhi cancer institute,

NEW DELHI.

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

• 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

• 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

• 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.

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

• 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.

• 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

• 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

• 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.

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

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

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

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 classificationGilly’s Stage I to II and to Sugarbaker’s PCI of less than 13.

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.

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 RLSugarbaker PH

• 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

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).

• 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

• 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.

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

Right upper quadrant peritonectomyFrom Sugarbaker

Cholecystectomy, lesser omentectomy and stripping of the omental bursaFrom Sugarbaker PH: Peritonectomy procedures

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

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

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)

Techniques & procedureOstomy ?

• 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 2004Eur J Surg Oncol 2006

Surg Oncol Clin N Am 2003

Timing of Bowel Anastomoses

• Before HIPECAdvantages

1. Reduce costs and operation time Disadvantages

1. Mechanical traction during perfusion can impair integrity of anastomoses

• After HIPECAdvantages

1. Effect of heat & chemotherapy on suture healing2. Possibility to treat bowel margins against eventual implantation of tumor cells

Disadvantages 1. Bowel edema so Technically more difficult.

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.

• 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.

true efficacy of HIPEC alone ineradicating the residual nonvisible disease after CCRS, applying the usual HIPECProcedure 2012

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

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

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

• Two main methods

• open abdomen technique and • closed abdomen technique. • mixed methods (semiopen or semiclosed)

have been reported.

Open method of HIPEC

Closed method of HIPEC

“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

• 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

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

• 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.

• 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.

• 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.

• 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.

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

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

Gastric cancer

• In 2011, Yang et al performed the first prospective randomized phase clinical trial Ⅲ 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.

• Prognostic factors – Completeness of

cytoreduction and – Presence of ascites.

Glehen et al 2010 n 159, retrospective review

• 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

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.

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.

– 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.

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

• 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

• 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

• 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

• 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

• 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.

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

• 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 )

Role of second look surgery

• 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

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.

• 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

• Divided treatment into time points: – Front-line, – Frontline failure (persistent disease at the end of

front-line treatment), – Consolidation(maintenance treatment)– Recurrent disease.

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 ..

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

here are no RCTs and the studies are heterogeneous

• 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%).

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.

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)

• 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

• 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.

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 havingPC and 29% being platinum resistant, the median OS was 23.5 months

• 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.

• 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.

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,

• 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]

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.

• 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.

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