**3. HIPEC indications**

The established concept of cytoreduction and HIPEC in peritoneal carcinomatosis is that they are to be performed in advanced stages of the disease, however more and more articles, starting with Sugarbaker and continuing with other high-volume surgical centers propose using HIPEC as a prophylactic measure not only in ovarian cancer but also in advanced appendiceal, colonic or gastric malignancies [11–19]. Keeping this in mind, it is our opinion that in the surgical management of ovarian cancer we will soon be able to classify HIPEC procedures into prophylactic – in stages up to II B and conventional – in stages III and IV. Because of the aggressiveness of the procedure, in each and every case we operate we struggle to achieve a complete cytoreduction, otherwise known as CC0 and in order to preoperatively assess in which patients this might be achieved we use staging scores such as the Fagotti score.

Initially, the Fagotti score [20] was described as a laparoscopic means of assessing the feasibility of a HIPEC procedure, but because all surgical manipulation of the peritoneum decreases the chances to perform a radical surgery, we substitute the laparoscopic Fagotti score with an imaging score based on a good quality abdominal and pelvic contrasted, diffusion weighed magnetic resonance imaging (MRI). Besides avoiding unnecessary manipulation of the peritoneum, we consider it superior to laparoscopy because it allows us to assess the areas of the abdomen and pelvis which are difficult to evaluate surgically, especially in a patient that has had previous abdominal surgery. Similar to it is also the Bristow CT score, but in our opinion the Fagotti score based on a good quality MRI examination is better [21].

The Fagotti score contains 5 variables – omental cake, diaphragmatic carcinomatosis, mesenteric retraction, bowel/stomach infiltration and spleen/liver metastasis. If present, each variable receives 2 points. If the Fagotti score obtained on the MRI is less than 8 we go ahead and prepare the patient for HIPEC, while if the score is higher than 8 we prefer to perform a Pressurized Intraperitoneal Aerosol

**113**

*Cytoreductive Procedures and HIPEC in the Treatment of Advanced Ovarian Cancer*

and pelvis with contrast and diffusion weighted imaging and a chest CT.

Chemotherapy (PIPAC) session, continue chemotherapy and reassess the patient by the same MRI score 4–6 weeks after. We can perform 2–3 such PIPAC sessions in the

Besides the Fagotti score which in our opinion is the best tool for staging ovarian peritoneal carcinomatosis and the Bristow score, there are several other scores which we only mention but not describe in detail as they are not used in case of ovarian cancer carcinomatosis – the Peritoneal Cancer Index (PCI) proposed in 1996 by Sugarbaker and Jaquet [15, 16], the Gilly staging [15, 17] and the simplified

In conclusion to this subsection on staging scores we would like to talk about our standard preoperative workup in cases which are referred to our center as candidates for cytoreductive surgery and HIPEC. This includes an MRI of the abdomen

We prefer MRI because in our experience it correlates best with what we would find on an exploratory laparoscopy allowing us to obtain a more accurate Fagotti score. The chest CT allows us to define the intrathoracic involvement and plan for an eventual diaphragmatic resection. We place bilateral chest tubes at the end of the procedure and if needed the chest drain can also be connected to the HIPEC machine in order to have cytostatic agent circulating also in the pleural cavity. Based on the imaging findings we can define not only the patients with better chances for having a complete resection but also those where there is a contraindication for HIPEC. The contraindications can be classified in absolute and relative.

• diffuse small bowel lesions in which resection would mean leaving less than

• locally advanced multiple relapses, resistant to different chemotherapy

Pleural involvement which is common, is not a contraindication for performing HIPEC, but rather an indication to also perform hyperthermic intrathoracic chemo-

Because of the variability of the moment when ovarian cancer is diagnosed there are several moments in the natural history of an ovarian cancer case when

*DOI: http://dx.doi.org/10.5772/intechopen.96405*

PCI system proposed by Zoetmulder [18].

Absolute contraindications are:

1 m of small bowel;

regimens;

• inoperable distant metastasis.

Relative contraindications are:

• progression under neoadjuvant therapy;

• bad performance status and comorbidities.

therapy (HITOC), eventually as staged procedures.

**4. Timing of the cytoreductive and HIPEC procedures**

• inoperable invasion of the liver hilum;

• diffuse, inoperable liver metastases;

• unresectable retroperitoneal lymph node masses;

hopes of achieving operability.

*Cytoreductive Procedures and HIPEC in the Treatment of Advanced Ovarian Cancer DOI: http://dx.doi.org/10.5772/intechopen.96405*

Chemotherapy (PIPAC) session, continue chemotherapy and reassess the patient by the same MRI score 4–6 weeks after. We can perform 2–3 such PIPAC sessions in the hopes of achieving operability.

Besides the Fagotti score which in our opinion is the best tool for staging ovarian peritoneal carcinomatosis and the Bristow score, there are several other scores which we only mention but not describe in detail as they are not used in case of ovarian cancer carcinomatosis – the Peritoneal Cancer Index (PCI) proposed in 1996 by Sugarbaker and Jaquet [15, 16], the Gilly staging [15, 17] and the simplified PCI system proposed by Zoetmulder [18].

In conclusion to this subsection on staging scores we would like to talk about our standard preoperative workup in cases which are referred to our center as candidates for cytoreductive surgery and HIPEC. This includes an MRI of the abdomen and pelvis with contrast and diffusion weighted imaging and a chest CT.

We prefer MRI because in our experience it correlates best with what we would find on an exploratory laparoscopy allowing us to obtain a more accurate Fagotti score. The chest CT allows us to define the intrathoracic involvement and plan for an eventual diaphragmatic resection. We place bilateral chest tubes at the end of the procedure and if needed the chest drain can also be connected to the HIPEC machine in order to have cytostatic agent circulating also in the pleural cavity.

Based on the imaging findings we can define not only the patients with better chances for having a complete resection but also those where there is a contraindication for HIPEC. The contraindications can be classified in absolute and relative.

Absolute contraindications are:

*Ovarian Cancer - Updates in Tumour Biology and Therapeutics*

**2. Historic perspective and rationale for HIPEC**

the combination of his technique with HIPEC [10].

locally by putting it in direct contact with the peritoneum.

**3. HIPEC indications**

Fagotti score.

Over time our view of peritoneal carcinomatosis evolved from considering it a terminal disease to considering it a form of locally advanced disease amenable to surgery which is sometimes with curative intent. The first to introduce the concept of cytoreductive surgery was Griffiths in 1975. His work shows a direct link between the radicality of the surgery and the survival of the patients [8, 9]. Five years later Spratt et al. show that hyperthermic intraperitoneal chemotherapy is feasible in peritoneal carcinomatosis [10, 11] and finally, in 1995 Sugarbaker et al. describe the technique of complete peritonectomy with an extraperitoneal approach, which in our opinion is the most suitable technique for most of the cases. He also described

If we look at the literature, we find articles clearly showing that the peritoneum in general and regions where scars exist – port sites for example are more prone to metastasis compared to solid organs and systemic chemotherapy is effective in about one third of the cases, with a complete response in only 15% of the cases [11]. Hence cytoreduction is extremely important to reduce tumor burden and HIPEC augments its efficacy by the lavage itself which, performed in a recent postoperative setting helps flush the cells resulted from manipulating bulky lesions such as is often the case. It also helps by activating heat shock proteins due to the temperature which is around 42 degrees and gives the chemotherapeutic agent a chance to act

The established concept of cytoreduction and HIPEC in peritoneal carcinomatosis is that they are to be performed in advanced stages of the disease, however more and more articles, starting with Sugarbaker and continuing with other high-volume surgical centers propose using HIPEC as a prophylactic measure not only in ovarian cancer but also in advanced appendiceal, colonic or gastric malignancies [11–19]. Keeping this in mind, it is our opinion that in the surgical management of ovarian cancer we will soon be able to classify HIPEC procedures into prophylactic – in stages up to II B and conventional – in stages III and IV. Because of the aggressiveness of the procedure, in each and every case we operate we struggle to achieve a complete cytoreduction, otherwise known as CC0 and in order to preoperatively assess in which patients this might be achieved we use staging scores such as the

Initially, the Fagotti score [20] was described as a laparoscopic means of assessing the feasibility of a HIPEC procedure, but because all surgical manipulation of the peritoneum decreases the chances to perform a radical surgery, we substitute the laparoscopic Fagotti score with an imaging score based on a good quality abdominal and pelvic contrasted, diffusion weighed magnetic resonance imaging (MRI). Besides avoiding unnecessary manipulation of the peritoneum, we consider it superior to laparoscopy because it allows us to assess the areas of the abdomen and pelvis which are difficult to evaluate surgically, especially in a patient that has had previous abdominal surgery. Similar to it is also the Bristow CT score, but in our opinion the

The Fagotti score contains 5 variables – omental cake, diaphragmatic carcinomatosis, mesenteric retraction, bowel/stomach infiltration and spleen/liver metastasis. If present, each variable receives 2 points. If the Fagotti score obtained on the MRI is less than 8 we go ahead and prepare the patient for HIPEC, while if the score is higher than 8 we prefer to perform a Pressurized Intraperitoneal Aerosol

Fagotti score based on a good quality MRI examination is better [21].

**112**


Relative contraindications are:


Pleural involvement which is common, is not a contraindication for performing HIPEC, but rather an indication to also perform hyperthermic intrathoracic chemotherapy (HITOC), eventually as staged procedures.

### **4. Timing of the cytoreductive and HIPEC procedures**

Because of the variability of the moment when ovarian cancer is diagnosed there are several moments in the natural history of an ovarian cancer case when cytoreductive procedures and HIPEC can be performed as can be seen in the analysis performed by Helm et al. [14].

The first such moment and the one in which cytoreduction and HIPEC give the best chances of survival is when the diagnosis is made, if complete cytoreduction can be achieved [2]. In the moment of diagnosis, depending on the extent of the disease we can talk about prophylactic HIPEC or conventional HIPEC in later stages [19]. Prophylactic HIPEC in ovarian cancer refers to stages I and II in which we have a cytology sample which is positive for tumor cells, which suggests an increased risk for peritoneal relapse and a decision is made together with the patient and the oncologist to perform HIPEC with a preventive thinking in mind.

Another moment for HIPEC and cytoreduction is after neoadjuvant chemotherapy, because most ovarian cancers respond well to chemotherapy and become operable after a neoadjuvant treatment. The only disadvantage is that it might downsize the peritoneal implants, rather than really downstage the tumor and thus hide implants that otherwise would have been resected, increasing the risk for recurrence.

HIPEC can also be performed as a consolidation therapy after neoadjuvant chemotherapy, meaning that it is performed during a second look laparotomy when peritoneal biopsies reveal residual disease.

Another occasion on which these procedures might become useful in ovarian cancer is when a peritoneal relapse is diagnosed and surgery is performed usually after a new course of neoadjuvant chemotherapy which will also determine the chemotherapeutic agent to be used based on the response of the tumor.

Finally, the last situation in which we would perform HIPEC is as a last resort treatment – basically a salvage procedure.
