**7. Description of the HIPEC procedure**

*Ovarian Cancer - Updates in Tumour Biology and Therapeutics*

vena cava and the right diaphragmatic crux

diaphragm;

• left colo-epiploic takedown

• dissection of the greater curvature

In the left upper quadrant, the peritonectomy means:

• resection of the peritoneum with or without the spleen

• dissection of the peritoneum covering the urinary bladder

In the lower abdomen the peritonectomy includes:

• dissection and section of the ovarian vessels

• sectioning the vagina below the cervix

• pelvic and paraaortic lymphadenectomy.

• appendicectomy

• sometimes colonic resections

• selective peritonectomy of the space between the caudate lobe, the inferior

• resecting the diaphragmatic peritoneum, sometimes with a piece of

• mobilization of the left colonic flexure, sometimes requiring a colectomy

• dissection of the ureters in order to expose and ligate the uterine vessels safely

• dissection of the peritoneum of the Douglas pouch when it is normal macro-

• sometimes a bladder resection or vascular resections might be necessary

In the central part of the abdomen the small intestine is examined carefully on both sides. Severely affected portions of the small bowel are resected carefully, keeping in mind in mind the risk for short bowel and taking away as little bowel as possible. Mesenteric implants are either resected or Argon beam coagulated. Atypical resections of the stomach can also be performed with the use of linear

Keeping in mind that the cytoreduction is usually followed by HIPEC we are faced with some delicate decisions regarding the anastomoses we perform. For small bowel we perform a 2-layer latero-lateral continuous suture without stoma. For colorectal anastomoses we perform a mechanical anastomosis using a circular stapler and protecting the anastomosis with a colostomy which we prefer to an ileostomy. And finally, there are cases where we do not perform an anastomosis but rather an end colostomy or ileostomy. These are mostly CC1 cases, posterior pelvic exenteration cases or total colectomy cases in fragile patients, even with a CC0 resection where an anastomosis would be too risky due to the status of the

scopically or with the rectum if there are visible tumor implants

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patient.

staplers.

For reasons related to the safety of handling cytostatic substances, most HIPEC teams in Europe, including our team use the "closed abdomen" technique in which the abdomen is closed permanently or only temporarily (the skin), with 4 drains inside, coupled to extracorporeal circulation device.

In short, the Rand Performer HT device that we use in our current activity, has the following components: 1) a heater or heat exchanger; 2) a pump system, which includes one or two peristaltic pumps; 3) a tank containing the infusion solution; 4) a circuit that distributes the drugs and heated fluid to the patient's peritoneal cavity. In 1999 the Italian Biomedical Company (RanD Biotech SRL, Medolla, Italy) was the first to develop a device dedicated to HIPEC, used especially for the treatment by hyperthermic perfusion of the peritoneal cavity. The most important advantage of this device (Performer HT) is its portability and adaptability for various purposes, as it can also be used to infuse isolated anatomical regions or organs, such as the treatment of an isolated limb or the separate infusion of the liver or lung. The Performer HT device ensures a flow rate of 100–2000 ml/min and it has up to 8 temperature monitoring lines in various areas of the peritoneal cavity, which has the ability to measure temperatures between 28 °C and 46 °C. In our practice we use tubes with a diameter of 28 Fr, two for inlet (1 - subdiaphragmatic and 1 - in the pelvis) and two for the outlet (1 - subdiaphragmatic and 1 - in the pelvis). We also use two lines for monitoring the intraabdominal temperature mounted in the pelvis and in the supramesocolic space. In terms of the perfused solution, we use 4–6 liters of warm transport solution (2/3 Ringer, 1/3 Voluven). Once an optimal infusion rate (> 800 ml/min) and an optimal intraperitoneal temperature around 42-43 °C is reached, the cytotoxic drugs are administered. We use Cisplatin (43 mg/L solution/m2) or Doxorubicin (15 mg/L solution) for carcinomatosis due to serous ovarian cancer. The duration of chemoperfusion is between 60 and 90 minutes. At the end of the procedure, the abdomen is rinsed with 3 liters of saline and the drains are left in place.

As to the choice of the chemotherapeutic drug, it takes into account the sensitivity of the tumor to platinum salts, which can be seen preoperatively by the response of the tumor to the neoadjuvant chemotherapy. Platinum-sensitive patients will follow the Cisplatin protocol, Platinum-resistant patients, the Doxorubuicin protocol.


Other types of protocols using Taxol, Oxaliplatin, 5 Fluorouracil or Mitomycin C, etc. are also cited in the literature.

## **8. Our experience**

In our experience we performed cytoreductive surgery and HIPEC on a number of 235 cases since we started performing these procedures in our hospital on the 5th of June 2013 which means an average of 33,5 cases/year. From a surgical point of view, critically speaking there were 2 stages: the initial experience 2013-December 2014, dominated by surgical caution, fear of complications, selective peritonectomy by "open" approach, after intraperitoneal exploration and the second stage, starting from January 2015, with the introduction of the Sugarbaker-Deraco extraperitoneal total peritonectomy technique, marked by increased aggression, the association of multiorgan resections often with digestive anastomoses.

Of these patients there were 188 (80%) females and 47 (20%) males. The mean age of the patients was 60,92 ± 10,64 years. The mean hospital stay was 9,23 ± 3,66 with a minimum of 4 days and a maximum of 32 days. In terms of overall survival, 182 out of 203 patients (89,65%) survived at 1 year and 15 out of 75 patients (20%) survived at 5 years. The mean operating time for these cases was 7,21 ± 0,7 hours and the mean PCI was 14,5 ± 0,3.

Because of the number of patients and the variety of the pathology we preferred to give a visual representation of the type of pathology approached (**Figure 3**), the type of chemotherapeutic agent we used (**Figure 4**) and whether or not we did a stoma and what type of stoma we did (**Figure 5**). In terms of the radicality of resection you can see in **Figure 6** the proportions of CC0, CC1 and CC2 resections.

Of particular importance in 2020, we had to reorganize our in-hospital protocols in order to ensure a COVID-free surgical department which allowed us to perform 29 cytoreductive procedures followed by HIPEC since the pandemic was declared on March 11th 2020. We were able to do this by thoroughly screening admitted patients by aligning ourselves to the guidelines emitted by the major surgical and

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**Figure 5.**

*Use of stomas in our experience.*

**Figure 4.**

*Cytostatic agents used in our experience.*

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

oncological international societies. Initially our screening consisted in PCR tests from nasopharyngeal swab, rapid antibody test and chest CT and according to the guidelines we started only performing PCR from nasopharyngeal swab, leaving rapid antibody and antigen tests and chest CT scans only for patients in which we

had a strong clinical suspicion of COVID and a negative PCR test [24].

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

**Figure 3.**

*Types of pathologies approached by cytoreduction and HIPEC in our experience.*

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

*Ovarian Cancer - Updates in Tumour Biology and Therapeutics*

multiorgan resections often with digestive anastomoses.

*Types of pathologies approached by cytoreduction and HIPEC in our experience.*

C, etc. are also cited in the literature.

and the mean PCI was 14,5 ± 0,3.

**8. Our experience**

Other types of protocols using Taxol, Oxaliplatin, 5 Fluorouracil or Mitomycin

In our experience we performed cytoreductive surgery and HIPEC on a number of 235 cases since we started performing these procedures in our hospital on the 5th of June 2013 which means an average of 33,5 cases/year. From a surgical point of view, critically speaking there were 2 stages: the initial experience 2013-December 2014, dominated by surgical caution, fear of complications, selective peritonectomy by "open" approach, after intraperitoneal exploration and the second stage, starting from January 2015, with the introduction of the Sugarbaker-Deraco extraperitoneal total peritonectomy technique, marked by increased aggression, the association of

Of these patients there were 188 (80%) females and 47 (20%) males. The mean age of the patients was 60,92 ± 10,64 years. The mean hospital stay was 9,23 ± 3,66 with a minimum of 4 days and a maximum of 32 days. In terms of overall survival, 182 out of 203 patients (89,65%) survived at 1 year and 15 out of 75 patients (20%) survived at 5 years. The mean operating time for these cases was 7,21 ± 0,7 hours

Because of the number of patients and the variety of the pathology we preferred to give a visual representation of the type of pathology approached (**Figure 3**), the type of chemotherapeutic agent we used (**Figure 4**) and whether or not we did a stoma and what type of stoma we did (**Figure 5**). In terms of the radicality of resection you can see in **Figure 6** the proportions of CC0, CC1 and CC2 resections.

Of particular importance in 2020, we had to reorganize our in-hospital protocols in order to ensure a COVID-free surgical department which allowed us to perform 29 cytoreductive procedures followed by HIPEC since the pandemic was declared on March 11th 2020. We were able to do this by thoroughly screening admitted patients by aligning ourselves to the guidelines emitted by the major surgical and

**118**

**Figure 3.**

oncological international societies. Initially our screening consisted in PCR tests from nasopharyngeal swab, rapid antibody test and chest CT and according to the guidelines we started only performing PCR from nasopharyngeal swab, leaving rapid antibody and antigen tests and chest CT scans only for patients in which we had a strong clinical suspicion of COVID and a negative PCR test [24].

In terms of multiorgan resections of note are cases of associations between posterior pelvic exenteration, right hemicolectomy and resection of liver metastases, resection of ureter, bladder horn and uretero-vesical reimplantation, total colectomy with extended jejuno-ileal enterectomy, entero-enteral anastomosis and right iliac terminal ileostomy, association of posterior exenteration with regulated left hepatic lobectomy and radiofrequency thermoablation of liver metastasis.

**Figure 6.** *Radicality of resection in our experience.*

**Figure 7.** *Intraoperative pictures showing multiple organ resections in a patient with recurrent ovarian carcinoma.*

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**Author details**

**9. Conclusion**

techniques.

**Acknowledgements**

**Conflict of interest**

which was used in this case.

Vlad Untaru1

Bogdan Moldovan1,2\*, Silviu-Tiberiu Makkai-Popa1

The authors declare no conflict of interest.

2 Academy of Science People in Romania, Romania

\*Address all correspondence to: bogdan.moldovan@spitalulsfconstantin.ro

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

and Doly Stoica1

1 "Sf. Constantin" Hospital, Brasov, Romania

provided the original work is properly cited.

, Costel Rad1

, Radu Pisica1

,

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

considered untreatable by other centers before coming in our service.

As an example, we would like to present a case of ovarian carcinoma recurrence in a 51 years-old patient previously operated and treated by chemotherapy. The PCI was calculated to be 19 and we performed a CC0 resection with a Sugarbacker extraperitoneal approach associated with a Hartmann resection, multiple liver resections, diaphragmatic resection with phrenic reconstruction, appendicectomy, omentectomy, HIPEC - Doxorubicin 80 mg 60 minutes at 42 °C. Some intraoperative pictures can be seen in **Figure 7**. The patient is still living at 3 years after the procedure and does not show signs of recurrence, despite the fact that she was

Cytoreductive surgery and HIPEC now offer an alternative to ovarian cancer patients that were once considered inoperable and in high-volume centers the complications are minimal. This chapter provides insight into the technique of cytoreductive surgery and HIPEC and presents our experience with these

The authors would like to thank the producers of the hyperthermic perfusion system – RanD for their excellent support in using the RanD Performer HT system

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

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

As an example, we would like to present a case of ovarian carcinoma recurrence in a 51 years-old patient previously operated and treated by chemotherapy. The PCI was calculated to be 19 and we performed a CC0 resection with a Sugarbacker extraperitoneal approach associated with a Hartmann resection, multiple liver resections, diaphragmatic resection with phrenic reconstruction, appendicectomy, omentectomy, HIPEC - Doxorubicin 80 mg 60 minutes at 42 °C. Some intraoperative pictures can be seen in **Figure 7**. The patient is still living at 3 years after the procedure and does not show signs of recurrence, despite the fact that she was considered untreatable by other centers before coming in our service.
