FRESH FROM THE PRESS August 2009

The latest issue of The Journal of Surgical Oncology pays a tribute to Dr. Paul H. Sugarbaker and Dr. Francios N. Gilly for pioneering Cytoreductive surgery and HIPEC as a treatment for Peritoneal Surface Malignancies.

Citation: Journal of Surgical Oncology 2009;100:285–286
Find it here: http://www3.interscience.wiley.com/journal/31873/home

I will post summaries of the articles in this issue of JSO over the next few days.

I hope you find them useful.

The issue that was published online four days ago, presents the papers that were presented in the 3rd annual International symposium on Peritoneal Carcinomatosis in Regensburg, Germany June, 2008. Just one year ago an issue was dedicated to the consensus meeting in Milan, since then a great volume of research has generated data to support the viability of this treatment modality for:
1- Pseudomyxoma Peritonei
2- Peritoneal Carcinomatosis from Colorectal cancer
3- Peritoneal Carcinomatosis from Gastric cancer
4- Peritoneal Carcinomatosis from Ovarian cancer
5- Peritoneal Mesothelioma.


Article (1) Surgical Technique of Parietal and Visceral Peritonectomy for Peritoneal Surface Malignancies.
Deraco, et al. Italy

The article discusses the standardized surgical techniques that were placed by Sugarbaker in 1995, 2002, and 2007. These techniques are critically assessed in light of 15 year experience at the National Cancer Institute of Milan, Italy.
Deraco and colleagues confirm that patients with PMP (119 of them in this series of 345 procedures) require an aggressive complete parietal peritonectomy even when the disease is localized. Because PMP is associated with a large volume of mucus, it is carried all around the abdomen with the flow of the peritoneal fluid and gravity in what Sugarbaker termed the Complete Redistribution Phenomenon.
The authors suggest some modifications on the Sugarbaker techniques and suggest collaboration with other centers to evaluate the significance and long term outcomes of these modifications for different PSMs. The authors give special attention to anastomoses, special precautions to preserve nerve function in the pelvic area, preservation of left gastric artery, prevention of pancreatitis. Although the center uses the closed technique for HIPEC no evaluation of this is offered here except in relation to its being associated with higher anastomosis leaks.

Article (2) Safety and Efficacy of Bidirectional Chemotherapy for Treatment of Patients With Peritoneal Dissemination From Gastric Cancer: Selection for Cytoreductive Surgery
Yunemora et al. Japan

60% of deaths from gastric cancer are caused by peritoneal carcinomatosis. CRS and HIPEC are associated with an improved survival when a complete cytoreduction is achieved. This study discusses the concept of bidirectional chemotherapy for peritoneal carcinomatosis from gastric cancer. This method which is called (NIPS)--Neoadjuvant intraperitoneal-systemic chemotherapy protocol-- uses both systemic chemo and intraperitoneal chemo at the same time to eradicate free-floating cancer cells in the abdomen (Peritoneal Free Cancer Cells). This is done to reduce tumor volume and therefore improve the chances of achieving a complete cytoreduction.
Patients are tested before and after NIPS for free-floating cancer cells by inserting a port into the abdominal cavity and obtaining a sample. Out of 79 patients, 65 (82.2%) had free cancer cells before NIPS, and the positive cytology changed to be negative in 41 (63.0%) patients after NIPS.
After NIPS a complete cytoreduction was achieved in 51.9% of patients with negative cytology but in only 14.8% of patients with positive cytology (P<0.001).>

1. NIPS using a port system is a safe and effective treatment for PC.
2. Peritoneal wash cytology through a port system is a good indicator for patient selection for complete CRS.
   
   

Article (3) Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies
POMPILIU PISO et al. Regensburg, Germany

This is a review of previous studies on the quality of life of patients who had the CRS and HIPEC. The literature shows that for long term survivals, patients felt they had impaired quality of life within 3 months after surgery, but then (after 6-12 months after surgery) they report same or better quality of life than they had before the surgery.
As for those patients with a limited life expectancy and high recurrence rate studies seem to indicate the following:

1. Patients with malignant ascites have a worse baseline assessment. But report better QoL immediately after surgery, and worse QoL in 12 months (probably because of the return of symptoms)
2. Depression appears to be a problem that continues to be reported by this group of patients and requires better care.
3. The author’s hypothesis is that the change in the number of participants in the various studies from baseline to 6 months post op is between 50-60%. They take this to mean that the sickest patients may have not been represented in these studies.
   
   In order to establish that the improved survival of patients after CRS and HIPEC comes with a better quality of life, the study recommends a standardized QoL assessment for all patients treated by CRS and HIPEC and to include this component in clinical trials.
   

Articel (4) Perioperative Management of Patients with Cytoreductive Surgery for Peritoneal Carcinomatosis

C. SCHMIDT et, al.

This article review all the factors that must be monitored during CRS and HIPEC by anesthesiologist and critical care physicians. This review summarizes perioperative changes in hemodynamics, oxygen supply, coagulation, hematopoetic parameters and fluid status during cytoreductive surgery and HIPEC and how to deal with these pathophysiological alterations.

1. Temperature management: During CRS hypothermia is caused by blood loss, extended exposure, drainage of ascites and lengthy procedure. So the patient must be warmed to keep the various bodily functions in tact (blood clotting rate, neurological status, and the ability to counter inflammation). During HIPEC, the body needs to be cooled down to avoid excessive heat from causing damage and oxygen levels need to be adjusted to meet the demands of increased metabolism.
2. Volemia: The study cautions that the closed-abdomen method of delivering HIPEC increases the intra-abdominal pressure which in turn affects cardiac output. So adjustment of fluids is needed here and monitoring the urinary output is a must to rule out renal failure.
3. Cardiac function:
4. Blood loss: understanding the influence of CRS and HIPEC on coagulation to prevent coagulation disorders.
5. Post operative management: ICU stay post op is indicated to monitor fluid levels and adjust IV fluids.
6. Pain management: supplementary epidural pain management is recommended to control pain and decrease need for a prolonged ICU stay.

Article (5) Indications and Patient Selection for Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy
SANTIAGO GONZA´ LEZ-MORENO et, al.

This study is based on the following premises:

1. CRS and HIPEC show unprecedented results in management of PSMs
2. Prognostic factors that contribute to better survival have been identified in earlier studies
3. This treatment involves a steep learning curve

Given these premises, the authors claim that there must be clear criteria for patient selection to ensure the best outcomes for patients.

Because the completeness of cytoreduction is the most important prognostic factor, patient selection criteria should be based on the possibility to achieve a complete cytoreduction.


Current imaging techniques are inaccurate and they do not allow a definitive judgment on achieving a complete cytoreduction.

Doctors should combat this shortcoming by identifying exclusion criteria, that is, definite indicators that a complete cytoreduction cannot be achieved.


Relative and absolute EXCLUSION criteria:

1. Other existing diseases that may prevent the patient from tolerating long surgery and anesthesia (cardiovascular, pulmonary, etc)
2. A high prior surgical score: if patient had extensive prior surgeries it may be difficult if not impossible to have a complete cytoreduction
3. Liver and Lung metastasis (unless it is localized a respectable )
4. The presence of segmental small bowel obstruction and/or significant mesenteric involvement, with loss of its architecture or vessel clarity on CT scan. Unless better images that are obtained by fat-suppression MRI allow a different assessment.
5. Patients who lack adequate motivation.
6. PCI >20 for colon cancer and PCI>10 for gastric cancer.
   

Recommendations:

1. Awareness must be created among general surgical community to make possible better exploration and description of the disease prior to CRS and HIPEC
2. Minimal intervention should be taken be general surgeons at first exploration (limited to biopsy whenever possible).
3. A process of referral to specialized centers should take place to improve outcomes.
4. Patients assessments should be conducted by a multidisciplinary panel of medical and surgical oncologists, radiologists, pathologists , nutritionists, gastroenterologists and anesthesiologists
5. Though some still call for phase III trials, there is currently enough evidence to adopt this treatment modality for patients who have the relevant PSMs and pass exclusion criteria.
   
   

*The article includes a table for indications and contraindications of CRS and HIPEC for PSMs.


Article (6)Learning Curve in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.
BIJAN N. MORADI and JESUS ESQUIVEL

A learning curve, in medicine, is defined as the effort required in mastering a new skill. In relation to CRS and HIPEC this means identifying the main elements in the learning process that can increase the chances of a complete cytoreduction while minimizing morbidity and mortality associated with the procedure.

Four studies on the learning curve are analyzed:

1. Smeenk et al Netherlands: The most significant increase in complete Cytoreductions occurred after ~130 procedures also decreased morbidity
2. Yan et al. Sidney: improved outcome over time in terms of morbidity and mortality and hospital stay, occurs after 70 procedures.
3. Cavaliere et al. Rome: small series of patients identified the learning curve as 19 months after which mortality dropped significantly.
4. Moran: Basignstoke: found a significant decrease in mortality and major morbidity over time and identified the main component of the learning curve in patient selection. Also claimed that the learning curve can be minimized with team work and having two experienced surgeons on the team.
   
   

Moradi and Esquivel claim that the studies show that there is progress over time but fail to identify the elements of the learning curve. Thus, they conclude “it is hard to document that a learning curve exists”. The improvement may be because of better mastering of surgical techniques or patient selection or both.

This is what the Moradi and Esquivel call ‘experience’ that is not transmittable but can be grounded in:

1. strict compliance with the predetermined patient selection criteria
2. familiarity with the surgical procedures,
3. and concentration of services to designated treatment centers

The real measure of success in learning this new skill is not the improvement of the percentage of complete CRS but the improvement in outcomes on the long run which reflects:

1. mastering the surgical skill
2. a knowledgeable process of patient selection
3. an understanding of the biological behavior of the different PSMs.