6 th International Workshop on Peritoneal Surface Malignancy. These notes were adapted from the slides shown at the presentations. Copyrights are owned by the authors. Please do not quote without their permission.
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DAY (1)9h00-9h30 : Opening Lecture – PH Sugarbaker (Washington, USA):Moving from consensus to clinical integration with the help of intracavitary pharmacology
T3 or T4 tumor
Positive peritoneal cytology
Peritoneal seeding on the serosal surface of the primary cancer
Adjacent organ involvement
Perforation of the primary tumor
Intraoperative rupture of a necrotic tumor mass
Limited peritoneal seeding
Intraoperative tumor spill
Resected primary colon cancer with carcinomatosis or high risk for carcinomatosis:
if the lymph nodes are negative: if the lymph nodes are positive:
3 months/physical conditioning folfox for 6 months /physical conditioning.
second look surgery
No carcinomatosis: carcinomatosis:
HIPECMoving from consensus to clinical integration with the help of the intracavitary pharmacology - PH Sugarbaker (USA)
1. In carcinomatosis evidence-based medicine supports the use of CRS+HIPEC over FOLFOX + Avastin.
2. Optimization of CRS + HIPEC need clinical trials but further clinical and pharmacologic studies will be of benefit
3. Second look surgery is indicated for patients at high risk for local-regional recurrence.
4. If possible, a CC-1 cutoreduction is always indicated.
A. a proportion of the patients are cured
B. it provides palliation
C. it best prepares the patient for subsequent systemic chemotherapy (log-kill hypothesis)
SUMMARY: Sugarbaker called for a multidisciplinary comprehensive care approach for delivering CRS/HIPEC. This is his argument:
DAY (1) of the intracavitary pharmacology - PH Sugarbaker (USA)9h30-11h00: Indications and place of imaging. Role of radiologists. Chairmen: F Cotton (Lyon, France), DL Bartlett (Pittsburg, USA)9h30-9h50: Cytoreductivesurgery and intraperitonel chemotherapy: which peritoneal surface malignancy should be treated ? Recommendations.P. Piso (Regensburg, Germany)9h50-10h10: What should be expected from imaging before cytoreduction for peritoneal carcinomatosis: the surgeon's point of view.S. Gonzales Moreno (Madrid, Spain)10h10-10h30: Imaging and peritoneal carcinomatosis: what should be preoperative exams? The radiologist's point of view.O. Pellet (Lyon, France)
Cytoreductive surgery and intraperitoneal chemotherapy: which peritoneal surface malignancy should be treated? Recommendations - P. Piso (Germany)
Selection peritoneal surface oncology group
Consensus Conferences 2006
Decision making: other factors
In a patient with DPAM we can perform laparoscopic HIPEC to treat recurrent ascites after CRS + HIPEC.
What should be expected from imaging before cytoreduction for peritoneal carcinomatosis: the surgeon’s point of view - S. Gonzales Moreno (Madrid, Spain)
CT scan in peritoneal carcinomatosis
Patient selection in mucinous peritoneal carcinomatosis
Volume of disease: minimal <0.5 cm: sensitivity of CT scan : 28% (true positives), 72% false negative (79 = number of observations)
Volume of disease : moderate 0.5cm to 5cm: sensitivity of CT scan : 72% (true positives), 28% false negatives (192= number of observations)
Volume of disease: Gross >5cm: sensitivity of CT scan : 90% (true positives), 10% false negatives (492= number of observations)
CT scan in peritoneal carcinomatosis
Patient selection in colorectal and appendiceal peritoneal carcinomatosis
CT scan in peritoneal carcinomatosis
Patient selection in advanced ovarian cancer
Attachment of the omentum to the spleen
Or disease greater than 2 cm on the
Liver surface or parenchyma
Suprarenal paraaortic nodes
What should be expected from imaging before cytoreduction for peritoneal carcinomatosis: the surgeon’s point of view - S. Gonzales Moreno (Madrid, Spain)
1. Enhanced CT of the thorax, abdomen and pelvis (oral, IV, rectal) is the current imaging standard to evaluate peritoneal surface malignancy patients for surgical exploration with the intent to perform complete cytoreductive surgery and HIPEC
2. We can expect:
3. Gadolimium-enhanced, fat-suppressed MRI is a good imaging complement to CT scan for the detection of subtle peritoneal, mesenteric or bowel surface disease, but its actual clinical integration in peritoneal surface malignancy practices is yet to occur
4. The role of PET/CT is limited to the detection of extraperitoneal disease. Its role in the evaluation of peritoneal disease extent is marginal.
Imaging of peritoneal carcinomatosis
PET/CT: negative points
Which means: Diagnostical use of CT :mdCT, Iodine contrast injection: e
PET-CT on its optimal use, PET –emdCT, should be the best imaging technique for the exploration of PC lesions combining morphological and functional data and providing a whole body acquisition.
Peritoneal carcinomatosis imaging requires a perfect coordination between radiological and surgical staffs.
Imaging and peritoneal carcinomatosis: what should be preoperative exams? The radiologist’s point of view O. Pellet (Lyon, France)
PET scan: mucinous tumors often do not light up therefore we have false negatives (but we have true positives as well)
The CT sensitivity on small bowel implants is 26%, it is 0% when using a PET scan.
The spatial resolution is better when using a CT scan but MRIs really depict soft tissue exceptionally. So they are worth exploring as an addition to CT scans. The MRIs are also precise for the detection of mesenteric retraction.
Since the PET scan provides the metabolic map and the CT provides the anatomic map, combining the two should provide us with greater sensitivity than any of them alone.
DAY (1) preoperative exams? The radiologist’s point of view O. Pellet (Lyon, France)11h30-13h00: How to improve patient selection. Role of general surgeons.Chairmen: V. Verwaal (Amsterdam, Netherland), H. Mahteme (Uppsala, Sweden)11h30-11h50: Place of laparoscopy for the evaluation of carcinomatosis extentM. Valle (Roma, Italy)11h50-12h10: Recommendations to general surgeons for preoperative peritoneal carcinomatosis discoveryB. Moran (Basingtoke, UK) \12h10-12h30: Selection of patients with colorectal carcinomatosis for a procedure combining perioperative intraperitoneal chemotherapy. Proposition of guidelines.M. Pocard (Paris, France)
Some variables must be noted by the general surgeons who assess the patients with PC:
Selection of patients with colorectal carcinomatosis for a procedure combining perioperative intraperitoneal chemotherapy. Proposition of guidelines - M. Pocard (France).
Major criteria (for exclusion)
1. Age over 70 years
2. Liver metastases multiple bilobular
3. OMS 2 or more
4. Serious medical histories (especially neurological or renal)
5. Clinical aggravation with systemic chemotherapy
7. Lung metastases
1. No drop markers with adjuvant chemotherapy
2. Being overweight (BMI>40)
3. History of pelvic irradiation
4. Carcinomatosis extended at the scanner or clinically significant
5. More than 4 surgical procedures
7. Associated metastases not resected – except ovary
Guidelines contraindication criteria
No criterion: indication for HIPEC – send the patient
One minor criterion: possible indication – contact a specialist
One major criterion or 2 minor criteria: not yet – back in 3 months
More than one major criterion or 3 minor criteria: no
DAY (1) procedure combining perioperative intraperitoneal chemotherapy. Proposition of guidelines - M. Pocard (France).14h30-15h45: Cytoreductive surgery. Technical aspects (Video-Photo)Chairmen: DM Kecmanovic (Belgrade, Serbia), P. Sugarbaker (Washington, USA)14h45-15h00: Bowel and mesentery disease. Anastomoses, Stomy – S. O’Dwyer (UK)15h00-15h15: Parietal disease. Parietal peritonectomy (gutters, cupula), scar removing – D. Bartlett (USA)15h15-15h30: Sus-mesocolic disease. Omental bursa, lesser omentum, cholecyctectomy and gastrectomy – V. Verwaal (Netherlands)
Peel peritoneum and trace uterers to insertion into bladder
Pelvic peritonectomy if diffusely involved
Scar removal, abdominal wall and gutters
7 region system
DAY (1) cholecyctectomy and gastrectomy by Verwaal16h00-18h20: Peritoneal Surface Malignancy. A multidisciplinary approach. Role of Anesthesiologists, Nutritionists, Nurses, Perfusionists.Chairmen: KH Link (Wiesbaden, Belgium), AC Beaujard (Lyon, France)16h20-16h40: Treatment of postoperative surgical complicationsA. Gomez Portilla (Vitoria, Spain)17h20-17h40: Intraoperative parameters that could be markers of morbidityS. Kusamura (Milan, Italy)
Carcinomatosis vs. conventional patients
Conventional patients Cytoreductionpatients
Previous surgeries 0 >1
Previous chemotherapy 0 >1
Parietal peritoneum present absent
Greater and lesser omentum present/absent absent
Parietal peritonectomies 0 >3
Visceral resections 1 >3
Bowel anastomosis 1 or 2 >2
Serosal tears unusual frequent
HIIC + EPIC no Yes
Empty cavity / dead space no Yes
Severe sepsis or C.I.D. unusual frequent
Abdominal compartment syndrome unusual frequent
The open vacuum abdomen is an optimal technique useful for temporary closure of the abdominal cavity in patients suffering abdominal complications after cytoreductive surgery.
A primary fascial closure was possible in 2/3 of the cases, 1 patient died, 2 developed enteric fistula.
All but one patient were discharged alive from the hospital.
Right diaphragmatic peritonectomy with glisectomy FIRST.
Avoid cytoreductions of more than 10 hours duration.
Although a colo-anal anastomoses is always performed, opt for an excluding derivative ostomy from the outset in case of more than 2 anastomoses.
Prompt reintervention when fistulas or the dehiscence of sutures are suspected or reveal themselves, and even in unidentified septic processes.
There are 4 markers of morbidity:
80% of the patients develop SIRS.
Prevention by methylprednisolone (MPS) of increased circulating TNF-a levels (Tumor Necrosis factor –a levels) and lung injury associated with SIRS due to intraperitoneal Hyperthermia
To investigate whether pretreatment with MPS may modulate serum TNF-a and lung injury in patients undergoing HIPEC.
CDDP dosage influenced the rates of post op complications
CDDP dose decreasing advisable if concurrent risk factors
Sepsis: the most frequent complication before death
Inflammatory/infective aspects promising future research
DAY (2) by Kusamura8h30-10h00: Colorectal Cancers. Chairmen: F. Antos (Prague, CZH), F. Cavaliere (Roma, Italy)8h30-8h50: Cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal carcinomatosis. Results of the French multicentric database.D. Elias (Villejuif, France)8h50-9h10: French ongoing trials in the treatment of peritoneal carcinomatosis from colorectal cancerF. Quenet (Montpellier, France)9h10-9h30: USA ongoing trials in the treatment of peritoneal carcinomatosis from colorectal cancerJ. Esquivel (Washington, USA)9h30-9h50: Long term of randomized study in colorectal carcinomatosisV. Verwaal (Amsterdam, Netherlands)
Cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal carcinomatosis. Results of the French multicentric database by Elias
Analysis of disease-free survival
Conclusion / colon –rectum
There are 2 other important prognostic factors:
Conclusion / Appendix cancer
Survival / complications:
Conclusion: Radicality of surgery is the most important prognostic factor.
Drug: Mitomycin C : The Dutch trial
1998-2001 105 patients
The first trial presented is relevant to PC from colorectal origin and whether HIPEC rather than CCR increases survival rate.
Trial is conducted in the following way:
The second trial is about a systematic second look surgery.
Discussion focused on the following:
DAY (2) carcinomatosis from colorectal cancer by Esquivel10h30-12h40: Rare Peritoneal Surface Malignancies and Place of PathologistChairmen: B. Moran (Basingstoke, UK), PJ Valette (Lyon, France), JC Sabourin (Rouen, France)10h30-10h50: Cytoreductive surgery and perioperative intraperitoneal chemotherapy for rare peritoneal disease. Results of the French multicentric database.O. Glehen (Lyon, France)0h50-11h10: The renewal of pseudomyxoma peritonei pathologyS. Bruin (Netherlands)11h10-11h30: New prognostics factors for peritoneal mesotheliomeM. Deraco (Milan, Italy)11h30-11h50: French National Organization for the treatment of rare peritoneal disease:RENAPE. From a national to an international cooperation.FN Gilly (Lyon, France)
Begins with presentation of current variety of definitions and pathological categories for PMP.
HIPEC literature reports
Appendiceal neoplasms associated with mucinous peritoneal disease:
Grading of mucinous peritoneal lesions according to different authors
Survival predictors for PMP
The study is based on the histopathological review of 269 patients with appendiceal and colonic tumors treated with HIPEC.
Studies evaluated the following features:
Histological classification of peritoneal surface malignancy:
Mucinous : 1. Disseminated Peritoneal Adeno Mucinosis
2. Peritoneal Mucinous Carcinomatosis
Non-mucinous : Peritoneal Carcinomatosis (PCA)
Primary tumor location and type of PSM: 71%: DPAM6% : PMCA-I14%: PMCA9% : PCAPSM from primary colon tumors: 37% mucinousDPAM most frequently from a primary appendix tumor29% of primary appendix tumors: non-DPAMSurvival analysisSignificant factors multivariate analysis Histological classification Gender Number of regions Result of cytoreduction HIPEC as first treatment on PSM Tumor locationA nomogram score (predictor of survival for individual patients) was created based on the theoretical assumptions of this studySummary:PSM is often mucinousDPAM carried better survival than PMCA and PMCA better than PCAFemale patients have better survival than male in mucinous PSMNon-mucinous tumors have worse survivalHistological classification of colorectal and appendiceal PSM give prognostic informationPSM should be classified by a standardized protocolHIPEC nomogram provides a tool for individual patient risk assessment.
French National Organization for the treatment of rare peritoneal disease: RENAPE. From a national to an international cooperation by FN Gilly
Dr. Gilly presented the French experience in creating a unified framework for the diagnosis and treatment of rare peritoneal disease. These include:
The aims of this national organization called RENAPE are :
The steps to be taken are as follows:
Cytoreductive surgery and perioperative intraperitoneal chemotherapy for rare peritoneal disease. Results of the French multicentric dtabase by Glehen. New prognostic factors for peritoneal mesothelioma by Deraco
DAY (2) chemotherapy for rare peritoneal disease. Results of the French multicentric dtabase by Glehen. 14h30-15h45: Gastric Cancer. Chairmen : P. Shen (WinstonSalem, USA), TD Yan (Sydney, Australia) 14h30-14h50: Place of hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis from gastric cancer. Results of French multicentric database.C. Arvieux (Grenoble, France)14h50-15h10: Neoadjuvant intrapertoneal chemotherapy in advanced gastric cancer.Y. Yonemura (Japan)15h10-15h30: Prevention of peritoneal carcinomatosis in gastric cancer.A. Garofalo (Roma, Italy)
Place of hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis from gastric cancer. Results of French multicentric database by Arvieux
StagePeritoneal carcinomatosis description
Stage 0No macroscopic disease
Stage 1Malignant implants less than 5 mm in diameter Localized in one part of the abdomen
Stage 2Diffuse to the whole abdomen
Stage 3Malignant implants 5 mm to 2 cm
Stage 4Large malignant nodules (more than 2 cm)
Bidirectional chemotherapy: Neoadjuvant IntraPeritoneal – Systemic Chemotherapy (NIPS)
The study aims to shows that NIPS (Neoadjuvant Intrapeitoneal Systemic chemotherapy) delivers good results in:
DAY (2) Garofalo15h45-17h30: Hyperthermic Intraperitoneal Chemotherapy: Unusual Indications.Chairmen: D. Elias (Villejuif, France), M. Gutman (Tel Aviv, Israel)16h05-16h25: Place of hyperthermic intraperitoneal chemotherapy as palliative treatment (ascites)S. Miska (Paris, France)
Laparoscopic HIPEC: methods
Laparoscopic HIPEC: results
Laparoscopic HIPEC : Conclusions
DAY (2) Garofalo17h30-18h45: FREE PAPER SESSION n°1Chairmen: S. Gonzales Moreno (Madrid, Spain), F. Quenet (Montpellier, France) Tuesday 17h46-17h54: Biological features are the dominant prognostics determinants for patients affected by pmp. Speakers: Dario Baratti, MD. Tuesday 17h54-18h02: Intraoperative Immunophotodetection: a new imaging technique to improve peritoneal surface malignancy diagnosis and treatmentSpeakers: Marian Gutowski, MDTuesday 18h10-18h18: Peritonectomy with high voltage electrocautery generates higher levels of ultrafine smoke particlesSpeakers: S. Naslund Andreasson, MD. Tuesday 18h18-18h26: Morbidity of intraperitoneal chemotherapy: effectiveness of eperidural anaesthesia / analgesia : a comparative study Speakers: G. Lorimier, MD,PhD. Tuesday 18h34-18h42: A phase II study evaluating the use of concurrent mitomycin C and capecitabine in patients with advanced unresectable pmp Speakers: Farquharson AL, MD.
This paper presents a multivariate analysis of PMP patients at 4 specialised centers (Washington, Wake Forest, Amsterdam, Milan).
Peritonectomy with high voltage electrocautery generates higher levels of ultrafine smoke particles Speakers: S. Naslund Andreasson, MD.
Morbidity of intraperitoneal chemotherapy: effectiveness of eperidural anaesthesia / analgesia : a comparative study Speakers: G. Lorimier, MD,PhD.
A phase II study evaluating the use of concurrent mitomycin C and capecitabine in patients with advanced unresectable pmp Speakers: Farquharson AL, MD
DAY (3) C and capecitabine in patients with advanced unresectable pmpWednesday, November 19th8h30-10h30:Pharmacokinetics and Biological SessionChairmen: F. Mohamed (Basingstoke, UK), B.Tranchand (Lyon, France)8h30-8h45: Pharmacokinetics of intraperitoneal cisplatiniumE. Cotte (Lyon, France)8h45-9h00: Effect of intraperitoneal pressure and adrenalin in pharmacokinetics of intraperitoneal drugsB. Chauffert (Dijon, France)9h20-9h40: New targeted therapy: Application for loco-regional therapyJF Pingpank (Bethesda, USA)9h40-10h00: Chemotherapy, environmental and juridic aspects.AC Sayag-Beaujard (Lyon, Frace)
Pharmacokinetics of intraperitoneal cisplatinium C and capecitabine in patients with advanced unresectable pmpE. Cotte (Lyon, France)Effect of intraperitoneal pressure and adrenalin in pharmacokinetics of intraperitoneal drugsB. Chauffert (Dijon, France)
There are 2 barriers for the distribution of chemotherapy:
There is not only the histological barrier to drug diffusion but also the drug draining through peritoneal and tumor vessels. The barrier is partially broken by epinephrine, an adregenic vasocontricting drug.
Therefore the platinum accumulation increases by IP and addition of epinephrine.
In microscopic PC there is no need of epinephrine. Epinephrine is important in millimetric PC and doesn’t play a role for advanced PC.
The abdominal pressure is another way to break the peritoneo-tumor barrier.
A 25mm Hg IP pressure for 2 hours is well tolerated in 50-60 kg pigs and it gives good staining of the peritoneum and mesentery.
There is also the possibility to increase the cytotoxicity by altering the osmolarity to increase the platinum accumulation in tumor nodules.
How to optimize IP protocols when tumor residues: pressure, osmolarity
New drugs: Gemzar appears to be very promising in vitro.
New targeted therapy: Application for loco-regional therapy C and capecitabine in patients with advanced unresectable pmpJF Pingpank (Bethesda, USA)Chemotherapy, environmental and juridic aspects.AC Sayag-Beaujard (Lyon, France)
DAY (3) C and capecitabine in patients with advanced unresectable pmpWednesday, November 19th11h00-12h00: FREE PAPER SESSION n°2 Speeches:Wednesday 11h08-11h16: Health related Quality of Lifein patients with peritoneal carcinomatosis after cytoreductive surgeryWednesday 11h16-11h24: Preoperative FDG-PET-CT correlates with intraoperative findings in patients with peritoneal carcinomatosisWednesday 11h24-11h32: HIPEC can influence theMalignant Ascites ProductionWednesday 11h32-11h40: Preliminary results of pancreatic cancer treated with surgical resection and HIPECWednesday 11h40-11h48: A pharmacologic analysis of perioperative administration of 5-Fluorouracil. Wednesday 11h48-11h56: Is neoadjuvant FOLFOX chemotherapy effective in patients with mucinous peritoneal carcinomatosis of appendiceal origin?Wednesday 11h56-12h04: Abdominal hyper-pressure in HIPEC
Preoperative FDG-PET-CT correlates with intraoperative findings in patients with peritoneal carcinomatosis.Speaker: Ingmar Konigsrainer, MD
HIPEC can influence the Malignant Ascites Production findings in patients with peritoneal carcinomatosis. Speakers: Frantisek Antos , MD, PhD. Preliminary results of pancreatic cancer treated with surgical resection and HIPEC Speakers: Antonios Apostolos K.Tentes , MD.
How do we know that ascites is really malignant?
Ascites: HIPEC + debulking:
With HIPEC 60% of the patients will not produce malignant ascites until their death. In 40% of the cases the ascites will form again but in the limited amount and without the need of punctures.
Median survival : 10 – 18 months
Gemzar is a potent cytostatic drug
HIPEC with Gemzar: 60 minute perfusion at a dose of 1000 mg/square meter
IV administration of Gemzar in case of infiltrated lymph nodes or for recurrent disease. The result of the treatment was that even in case of recurrence all the failure sites were distant and not loco-regional (liver metastases)
5-FU is an inhibitor of thymidylate syntetase. It has a low molecular weight so theoretically it shouldn’t be the ideal choice for HIPEC. However, 5-FU largely stays in the peritoneal cavity and it is rapidly metabolized which is a compensation for its low molecular weight. The fact that it is rapidly metabolized practically means that it has a very high concentration immediately after use, only 7 minutes after instillation. So it has a rapid distribution to all body compartments and its metabolisation is restricted to the plasma compartment.
Rapidly transponded to all compartments and to some degree to the tumor nodules = true pharmacological end point.
Is neoadjuvant FOLFOX chemotherapy effective in patients with mucinous peritoneal carcinomatosis of appendiceal origin? Speakers: Dal Yoo, MD.
DAY (3) with mucinous peritoneal carcinomatosis of Wednesday, November 19th13h30-15h30: Ovarian CancerChairmen: G. Freyer (Lyon, France), AA Tentes (Didimotichon, Greece)14h30-14h40: Perspectives in clinical research for the treatment of peritoneal carcinomatosis in ovarian cancerM. Deraco (Milan, Italy)