The peritoneum is the serous membrane covering the abdominal wall from the inside and some organs from the outside (including: stomach, part of the duodenum, small intestine and most of the colon, uterus and ovaries). Metastasis of malignant tumours to the peritoneum is referred to in the TNM classification (T-tumour- tumour, L-lymph nodes - lymph nodes, M- metastasis - metastasis) as distant metastasis, i.e. the M+ feature, and is generally associated with a poor prognosis and a short survival time for untreated patients (approximately 6 months on average). Intraperitoneal chemotherapy in hyperthermia is a salvage procedure for many of them.
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Patients with peritoneal metastases confirmed by imaging studies (MRI magnetic resonance imaging, CT scan, PET scan) and at the same time with no other secondary metastases, e.g. metastases to parenchymal organs such as the spleen, liver or brain, or which are small and can be effectively treated with surgery or radiotherapy, are sometimes offered cytoreductive surgery with chemotherapy administered directly into the body cavity - the peritoneum. This method allows very good treatment results even in locally significantly advanced patients.
The procedure consists of two stages: firstly, after an initial revision of the abdominal cavity and assessment of the operability of the tumour, cytoreduction is performed - the most thorough, meticulous removal of masses spread on the peritoneal surface, sometimes with tumour-lesion organ tissues (e.g. fragments of the small intestine, large intestine, liver, gonad). These procedures are technically very difficult and lengthy - the operative time can be up to several hours. They require endurance from the medical staff, perfect precision acquired through many years of practice working with oncology patients. Once the surgical part has been completed, perfusion begins - after connecting the delivery tubes, the cytostat is administered in infusion fluid heated to a high temperature above the physiological temperature of the human body. The effective circulation time of chemotherapy in the peritoneal cavity varies depending on the drug administered - from 30 minutes to two hours.
Proper patient qualification is essential for the success and safety of the procedure. In spite of their advanced stage of oncological disease, they must be in a satisfactorily good general and physical condition to withstand - in addition to the burdensome surgery - the possible complications resulting from the topically administered cytostatics themselves as well as the many hours of general anaesthesia and the postoperative period.
Which cancers are indications for HIPEC?
Not all malignancies can give rise to secondary peritoneal lesions. They are most commonly found in the course of ovarian cancer, even in patients undergoing primary radical surgery with subsequent adjuvant treatment. They are less common in the course of gastric cancer, but here they pose a serious clinical problem - they are sometimes found even at the time of primary diagnosis and the disease progression is so high that effective oncological treatment (combined surgery with radio and chemotherapy) is not possible. However, when the peritoneal lesions are limited to a small area and it is possible to remove the stomach and perform some ileo-oesophageal anastomosis within the limits of healthy tissue, HIPEC surgery may be considered, after careful evaluation of the indications and contraindications, as an alternative to complementary treatment(chemotherapy). A common cancer whose metastases are found in the peritoneum is colorectal cancer - up to 15 per cent of patients in long-term follow-up. Patients are diagnosed for recurrence even several years after completion of oncological treatment, for example because of persistent symptoms of gastrointestinal obstruction, sometimes associated with adhesions after surgical interventions.
Not only are secondary intraperitoneal lesions an indication to consider HIPEC- patients with primary peritoneal tumours may also be eligible. Pseudomyxoma of the peritoneum (pseudomyxoma peritonei) is a rare neoplasm whose starting point may be the appendix (more common in men), or the ovary (in women). It is often histologically benign, but due to the production of large amounts of mucous masses, it is referred to as locally malignant - symptoms as in the course of a highly advanced malignant proliferative process, with low cytological malignancy of the cells building up the tumour mass. In less specialised centres, sometimes salvage surgery is performed - repeatedly, to remove the mucinous masses - but this is only symptomatic. Peritoneal mesothelioma (mesothelioma peritonei), like mucormycosis, is a rare tumour. The primary starting point here is also the peritoneum itself. In highly specialised centres, cytoreductive surgery and intraperitoneal hyperthermia perfusion chemotherapy are the treatment of choice for these tumour types. The decision to qualify for HIPEC treatment is made on an individual basis, with the possibility of radical resection as the main consideration.
How do peritoneal metastases form?
The mechanisms of metastasis are known, complex and dependent on many factors. Most commonly, they occur when a tumour growing originally, e.g. in the colon, in the ovary is so advanced that it occupies the entire tuberous wall of the organ with infiltration of the outer layers and the covering peritoneum. Tumour cells can flow freely from the primary tumour mass and move within the peritoneal cavity and nestle anywhere within it. Chemotherapy administered systemically (intravenously) because of the poor blood supply to the mural peritoneum has little effect on them. The spread of tumour cells can also occur during the primary surgical procedure - when the tumour metastases into surrounding nodes or cut lymphatic vessels and when the tumour tumour disintegrates due to technical difficulties or careless preparation.
Secondary lesions may occupy virtually any region of the peritoneum, but are most commonly located in the area of the primary lesion and, because of the direction of peritoneal fluid flow, its gravitational descent, are found in the peritoneum covering the pelvic floor (bladder area, upper rectum, cecum, reproductive organs).
Symptoms
Tumour spread to the peritoneum is morphologically small nodules occupying the mural or visceral peritoneum, causing organ "clumping" and subsequent symptoms of gastrointestinal obstruction - a situation that often requires emergency surgical intervention. Localised in the urinary tract area, they can cause urinary stasis in the kidneys and their secondary failure. The irritated peritoneum reactively produces transudate fluid, leading to increasing symptoms of ascites. Sometimes, in particularly advanced cases, it is not technically possible to perform surgery with the intention of cure - due to massive infiltration of organs in the abdominal cavity, where the benefit to the patient would be disproportionately small to the high risk of surgical intervention as well as general anaesthesia.
Qualification
As mentioned, several conditions must be met. The first is the restriction of tumour spread to the peritoneal cavity, confirmed by imaging studies (MRI, CT, PET). The presence of distant metastases via the blood route (with the exception of a single lung metastasis and single resectable or thermoablative colorectal cancer metastases to the liver), is a contraindication to HIPEC due to its unfavourable prognosis regardless of the success of the cytoreductive procedure. The second prerequisite is the limited extent of peritoneal metastatic lesions - the possibility to remove them, confirmed by imaging studies. The presence of lesions at anatomically critical points that cannot be removed without endangering the patient's health and life indicates that the procedure should be abandoned.
In patients with symptoms associated with advanced cancer (obstruction, abdominal pain, vomiting, weight loss, respiratory problems, cancer cachexia), the decision to proceed with the procedure should be analysed very carefully. Another verification of the operability of the lesions takes place during the laparotomy, after opening the abdominal integuments - assessing whether it is technically possible to resect all the structures occupied by the cancer, as imaging studies cannot always be fully relied upon.
The Sugerbaker Peritoneal Cancer Index (PCI) scale is used to assess operability prior to resection of lesions. This is a scoring scale that divides the peritoneum covering the abdominal cavity and small bowel into 13 areas in which the number of metastases is assessed (the number of points can range from 1 to 39). The cut-off point, the therapeutic benefit is associated with cytoreductive surgery and HIPEC, is considered to be 20.
The extent of excision may include not only part of the peritoneum, but also part of the large intestine with the upper part of the rectum, part of the stomach, sections of the small intestine, the greater web, the gallbladder, part of the liver, the spleen, the ovaries, the uterus, part of the bladder wall. After surgical removal of all macroscopically visible tumour foci, the next stage of the procedure - intraperitoneal hyperthermic intraperitoneal chemotherapy (HIPEC) - is started. The fluid (Ringer's lactate, 0.9 % NaCl or 5 % glucose solution) with the dissolved cytostatics is administered through the delivery drains continuously in a closed circuit - it circulates from half an hour to 120 minutes, under elevated temperature conditions between the patient's body and the instrument that pumps and heats the fluid. Four drains are inserted into the peritoneal cavity: two feeding the perfusion fluid (supply) and two receiving. Each of these drains is fitted with a thermometer to measure the temperature of the fluid entering and leaving the peritoneal cavity, so as to maintain a constant temperature above 43 degrees Celsius.
The elevated temperature of the perfusion fluid itself has a damaging effect on tumour cells. In addition, it increases the penetration of cytostatic drugs into the tumour tissue and enhances their anti-tumour effect. The drugs most commonly used in the HIPEC procedure include cisplatin and mitomycin C, oxaliplatin, doxorubicin. After completion of the perfusion of the cytostatic fluid, the abdominal cavity is flushed with clear perfusion fluid.
HIPEC, as you can see, is a highly taxing procedure, but it is an opportunity for many patients who previously had no prospect of a cure.
