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Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013.

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Cytoreduction, Peritonectomy and Hyperthermic Antiblastic Peritoneal Perfusion for the Treatment of Peritoneal Carcinomatosis

* and .

* Corresponding Author: Department of Surgical Oncology “S Giuseppe” Hospital, Empoli, Florence, Italy. Email: /

Generalities and Indications

Peritoneal carcinomatosis may present as synchronous disease or like evolution of gastrointestinal or female genital tumors (including pseudomyxoma peritonei, a variable malignancy myxoid tumor, arising from the appendix). It is also the common way of presentation of primitive peritoneal tumors (like peritoneal mesothelioma). Peritoneal carcinomatosis has been considered nearly impossible to treat with surgery till few years ago. Moreover, the results obtained with systemic chemotherapy were poor. In the ‘80s’ some authors developed and improved a new combined technique to manage peritoneal carcinomatosis, consisting in cytoreduction of neoplastic lesions, peritonectomy (removal of peritoneum macroscopically affected from tumor) and hyperthermic antiblastic peritoneal perfusion (H.A.P.P.). Carcinomatosis nodes usually affects peritoneum in preferential sites as the pelvis, the ileum-caecal angle, the right diaphragm and retrohaepatic space, the lesser omentum, the left diaphragm and paracolic spaces. In fact, in these regions the peristalsis is less effective, there are the points of peritoneal fluid absorbtion and, finally, these areas are particularly anfractuous, with virtual spaces, so the circulation of fluids is slow and neoplastic cells may easily lodge. At least, cells may deposit under action of the force of gravity. For these reasons, peritonectomy is particularly indicated in these regions. The rationale of combining hyperthermia and chemotherapy has been described in previous chapters. The peritoneal cavity can be considered a “pharmacological sanctuary” for the presence of the peritoneal-plasmatic barrier, that is independent from mesothelial layer, and preserves the leakage to systemic circulation of high molecular weight drugs as Cisplatinum, C-Mytomicin, Doxorubicin, Oxaliplatinum. So it's possible the use of an high concentration of cytostatic drugs into the tumor area, with mild side-effects. The H.A.P.P. has maximal efficacy when all the macroscopic disease has been removed with cytoreduction and peritonectomy. There is loss of efficacy on nodules bigger than 3 mm, because this is the maximal depth that the drugs can reach, even in hyperthermic condition.

The techniques described to perform the H.A.P.P. are three: “closed”, “open” and “semiclosed” one. In “closed” technique, the perfusion is performed when the operation is completed and the abdomen is closed, using tubes placed during the surgical time. The most important problem described with this technique is the difficulty to reach homogeneous distribution of temperature and drugs into the abdominal cavity. Moreover, a visual and manual control of the abdomen is not possible during the perfusion. The “open” technique has been described by P.H. Sugarbaker, it consists in perform the perfusion when the abdomen is still open, hanging all the abdominal wound to an autostatic retractor placed upon the incisional area (Coliseum technique). This way, during perfusion, the surgeon may check the abdominal cavity, and stir the peritoneal solution, to obtain an homogeneous distribution of drugs and temperature. The criticism is related both to the large loss of temperature from the wide abdominal incision, and to the possibility of leakage of drugs from the abdomen. In the original “semiclosed” technique, the abdominal wall is partially closed and hanged to the autostatic retractor, only the central part of the incision remains open (Fig. 1). Through this small opening, the surgeon can mix the perfusate solution and check what happens in the abdomen. Those contrivances consent both the homogeneous distribution of temperature and drugs and low risk of drug leakage from the abdominal cavity. In our opinion, this kind of procedure collects the advantages of the other two techniques and reduces their drawbacks. Briefly, the semiclosed technique permits: (1) manual distribution of temperature and perfusate; (2) rapid reaching of ideal temperature for H.A.P.P.; (3) to perform anastomosis after H.A.P.P., so all the bowel surfaces are exposed to drugs; (4) reduction of drugs leakage from wound margins, with major safety for the operatory room-staff.

Figure 1. Semiclosed H.

Figure 1

Semiclosed H.A.P.P.: the skin is hanged with Backaus forceps and self-blocking strings to the self-retaining retractor. The surgeon's hand mixes the perfusate through the PVC sheet fixed to the edge of the incision, in order to distribute the drug and (more...)

Surgical Techniques

Peritoneal perfusion is really effective only if preceeded from aggressive cytoreductive surgery. So surgery becomes mandatory in treatment of peritoneal carcinomatosis. Some techniques of “centripetal” aggression of tumor have been codified. They are known with the name of peritonectomy, and they allow to remove both visceral lesions and the peritoneum infiltrated by the carcinosis. Six different techniques of peritonectomy are described: (1) Epigastric peritonectomy consists in the “en bloc” removal of previous scare, round and falciform haepatic ligaments (Fig. 2); (2) Central peritonectomy consists in greater omentectomy with removal of the superficial layer of transverse mesocolon (Fig. 3). Sometimes it's necessary the removal of the spleen “en bloc” with the omentum, associated to peritoneal stripping of right and left abdominal wall; (3) Right diaphragmatic peritonectomy (Fig. 4), with liver mobilization and removal of the right diaphragmatic peritoneum and the peritoneum covering the right adrenal gland, right kidney and duodenum (Fig. 5); (4) Left diaphragmatic peritonectomy, with removal of peritoneum covering the left adrenal gland and left kidney (Fig. 6); (5) Lesser omentum peritonecomy, consisting in cholecistectomy, peritoneal removal from porta haepatis, removal of lesser omentum and of the tumor near the caudate lobe (Fig. 7); Pelvic peritonectomy with “en bloc” removal of rectum and sigmoid colon, uterus and adnexa, and removal of vescical peritoneum (Fig. 8). Peritonectomies are performed when an highly aggressive surgery is indicated (for example in the Pseudomixoma Peritonei, a tumor characterized by large diffusion of mucinous carcinosis, with low malignancy rate). Peritonectomies are varying combined with resections of viscera involved in the neoplastic invasion. Resection of rectum and sigmoid colon, hystero-oophorectomy, splenectomy, omentectomy and colecistectomy are common procedures in the treatment of peritoneal carcinomatosis. Total gastrectomy is rarely performed. The “en bloc” visceral resection with adjacent peritoneum maybe required, because of massive neoplastic infiltration. The approach is completely extra-peritoneal (the routine approach for the pelvis).

Figure 2. The access to the peritoneal cavity is lateral and not on the midline, in order to remove the epigastric peritoneum and the eventual previous surgical scares.

Figure 2

The access to the peritoneal cavity is lateral and not on the midline, in order to remove the epigastric peritoneum and the eventual previous surgical scares. In the picture the previous scare is kept with the forceps.

Figure 3. When omentectomy in performed, it is possible to see the great curvature after peritonectomy.

Figure 3

When omentectomy in performed, it is possible to see the great curvature after peritonectomy. In the low part of the picture the colon is kept with the forceps.

Figure 4. Right diaphragmatic peritonectomy.

Figure 4

Right diaphragmatic peritonectomy.

Figure 5. Right diaphragmatic peritonectomy completed.

Figure 5

Right diaphragmatic peritonectomy completed. It is possible to see the diaphragmatic muscle, the lower face of he liver, the right antero-lateral part of caval vein after peritonectomy.

Figure 6. Diaphragmatic peritoneum with massive carcinosis from pseudomixoma peritonei.

Figure 6

Diaphragmatic peritoneum with massive carcinosis from pseudomixoma peritonei. The peritoneum is removed from the posterior fascia of the rectum muscle and it is kept with forceps.

Figure 7. Lesser omentum peritonectomy is completed.

Figure 7

Lesser omentum peritonectomy is completed.

Figure 8. Pelvic peritonectomy is completed.

Figure 8

Pelvic peritonectomy is completed.

Semiclosed H.A.P.P. Technique

When the surgical time is completed, the H.A.P.P. is performed. The “semi-closed” method consists in placing 5 drain tubes into the abdominal cavity: the inflow ones are two and have multiple holes. They are Y-shaped and present 4 diffusion lines for the homogeneous distribution of drugs into the abdominal cavity (1 subdiaphragmatic branch, 1 sovramesocolic branch, 1 among the ileal loops, 1 in the pelvis). Three outflow tubes are placed respectively in the pelvis and in the subdiaphragmatic spaces (Fig. 9). Backaus forceps are used to close the cranial and caudal portion of abdominal wound. The skin is then suspended to self-retainig retractor (placed at more or less 15 cm from abdomen) by plastic self-blocking strings. This kind of placement creates the virtual cavity needed to perform the H.A.P.P. The central portion of the wound is suspended to the retractor too and covered with a PVC sheet that presents a hole in the middle (Fig. 1). The drain tubes are connected to a perfusion system formed by two pumps and a heat exchanger to heat the perfusion liquid. The 2 pumps (inflow and outflow), are connected through a reservoir, so it's possible to reach a continuous circulation of the perfusate at the speed of 1 lt/min. The pumps are checked by a computed system, that controls the flows and the heat exchanger. Three intraperitoneal temperatures are checked by probes, moreover, it's important the measure of inflow, outflow and patient's oesophageal temperature. Temperature is a critical factor; when it's higher than 44°C, the recovery of intestinal anastomosis can be delayed, and generally the risk of postoperative intestinal perforations is increased. On the other hand, when temperatures are too low, the effectiveness of drugs in strongly decreased. The amount of the circulating perfusate (solution for peritoneal dialysis) is calculated considering the patient body surface. The drugs employed are different and choosen on neoplasia's hystological type. Currently, the drugs of choice are CDDP, C-Mitomycin, Doxorubicin, Oxaliplatinum, differently combined and associated. During perfusion, the surgeon mixes the perfusate using his hand through the hole in the PVC sheet. When intraperitoneal temperature of 41.5°C is reached, the drugs are added to the circuit and the H.A.P.P. is performed for 60 minutes. During the perfusion, an iced helmet is placed on patient's head, and cold liquids are infused i.v., to prevent systemic hyperthermia. A diuresis higher than 120 ml/10minutes is suitable to prevent renal complications.

Figure 9. Scheme of position of the tubes in the abdominal cavity to perform the H.

Figure 9

Scheme of position of the tubes in the abdominal cavity to perform the H.A.P.P.

Clinical Experience and Results

From October 1995 to January 2005 we performed 235 operations for peritoneal carcinomatosis. In 70 cases we only performed surgery (28 explorative laparatomies and 42 debulking and peritonectomies without H.A.P.P.); in 165 cases we performed cytoreduction and H.A.P.P. The peritoneal carcinomatosis arose from: ovarian cancer in 44 cases (two protocols have been activated for ovarian cancer: in 19 cases the disease was at the first relapse, with carcinomatosis, after one line of chemotherapy, with a disease free interval of 3 months at least. In 25 cases the disease was plurirelapsing); colorectal cancer in 32 cases; pseudomixoma peritonei (PMP) in 37 cases; peritoneal mesothelioma in 26 cases; abdominal sarcoma in 14 cases; gastric cancer in 6 cases; other cancers in 6 cases (endometrial carcinoma, small cell desmoplastic tumor, etc.). In the patients who underwent cytoreduction + H.A.P.P., morbidity was 18,8% (31/165) and perioperative mortality was 4.8% (8/165). Most common complications were sepsis, postoperative haemorrhage (even after 72/96 hours from the operations), dehiscence of intestinal anastomosis, mild acute renal failure, temporary medullary aplasia, A.R.D.S.

Classification of Results per Pathology

PMP: all complete cytoreduction; 32 patients are alive without evidence of disease (the longest follow-up is 8 years), 4 patients are alive with disease, 1 patient died of disease with relapse after only 6 months from operation.

Colonic Cancer: 23 patients have been treated with a protocol using CDDP and Cmytomicin, without very satisfactory results, with a median survival time of 14.5 months; the last 9 patients have been treated with a new protocol (Elias is the author proposing this treatment) providing a careful selection of patients and the employment i.v. of 5-FU and folinic acid, followed by H.A.P.P. with oxaliplatinum. Although the results are still too recent for a statistical evaluation, the first patient has been operated more than 2 years ago and he is not yet presenting relapse of disease.

Ovarian Cancer: in 19 patients at the first relapse after 1 line of chemotherapy and DFI ≥ 3 months, the median survival time is 726 days. For the 25 patients with plurirelapsing disease, the median survival time is definitely shorter: 427 days.

Mesothelioma: in the patients who underwent cytoreduction and H.A.P.P. morbidity was 21%; 3 patients presented ARDS. The median survival time is 40 months.

Sarcoma: the results are not statistically valuable.

Gastric Carcinoma: results in our casuistry were very poor, with a median survival time of about 6 months. Those results, combined to aggressiveness of the treatment brought us to quit this technique for patients with peritoneal carcinomatosis from gastric cancer. Anyway there are some Authors reporting good results in the treatment with neo-adjuvant intent of gastric cancer with serosal invasion, without evident peritoneal carcinomatosis at the moment of operation.


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