Pseudomyxoma peritonei - detailed information

What is it?

Pseudomyxoma peritonei is often a slowly progressive disease that produces extensive mucus accumulation within the abdomen and pelvis.

There are two clinically distinct groups of peritoneal mucinous lesions. The first can be described as low-grade mucinous carcinoma peritonei (MCP-L) which would include mucin producing disease from an appendiceal adenoma to a well-differentiated mucinous carcinomatosis or well-differentiated variants of mucinous adenocarcinomas. The second group can be described as high-grade mucinous carcinoma peritonei (MCP-H) and would apply to either moderately or poorly differentiated adenocarcinomas.

In pseudomyxoma an adenoma arises within the appendix and as it grows it occludes the lumen of the appendix. This can be classified as a low-grade appendiceal mucinous neoplasm (LAMN). The appendix eventually ruptures leaking mucous containing epithelial cells into the abdominal cavity leading to low-grade mucinous carcinoma peritonei. After the appendix decompresses the perforation may reseal only to extrude more adenomatous epithelial cells at a later time.

Sometimes neither a primary appendiceal tumour nor a normal appendix is apparent. In these cases it may be that the appendix has ruptured and has been obliterated by the developing fibrosis. PMP is often referred to as being a 'borderline malignant' condition. The tumour is not biologically aggressive because it does not metastasise via the lymphatics or blood stream like gastrointestinal adenocarcinomas, however, it is still a fatal process. The space required within the abdomen and pelvis for nutritional function eventually becomes replaced by mucinous tumour.

Most of these tumour cells are surrounded by fluid of varying consistency. Bulky cellular deposits are usually found within the omentum and beneath the right hemidiaphragm. Gravity creates a further accumulation of adenomucinous cells within the pelvis where the peritoneum reflects over the pelvic organs.

Common sites involved in tumour dispersion also include the stomach, the area around the terminal ileus and the rectosigmoid colon within the pelvis. All three of these sites are fixed to the retroperitoneum and are not free to move as a result of peristaltic activity. The peristaltic activity of the small bowel may prevent mucinous tumour implantation on these surfaces resulting in relative sparing of the small bowel.

What causes pseudomyxoma?

For the majority of people with true pseudomyxoma an adenoma is found in the appendix. Like many other tumours, pseudomyxoma can occur in people who lead healthy lifestyles.

Signs and symptoms

For women and men the most predominant feature is a gradual increase in abdominal girth. This increases pressure on the gut and prevents the patient from eating normally. Despite this the patient often notes an increase in body weight. The symptoms can be non-specific and are often misdiagnosed.

How is it diagnosed?

The diagnosis of pseudomyxoma can be difficult. It is often an unexpected finding during investigations of non-specific abdominal symptoms, either on USS/CT scan or the patient has undergone an abdominal operation. The diagnosis of pseudomyxoma can be difficult since mucinous tumours may be present in the gastrointestinal tract, gallbladder and in the ovaries.

Women with both low-grade mucinous carcinoma peritonei and high-grade mucinous carcinoma peritonei often have ovarian involvement by mucinous tumour. The ovarian tumour is often the presenting clinical symptom or sign and is often assumed to be the primary site, therefore no attempt is made to identify the appendix as a possible source of mucinous tumour.

In some cases the primary tumour in the appendix can be quite inconspicuous in the context of abundant mucinous peritoneal tumour. In addition, rupture and fibrosis can obliterate the appendix. Other problems are that ovarian tumours are often interpreted pathologically as primary mucinous borderline malignant tumours. This happens particularly when the appendix has not been removed but even occurs when an appendiceal adenoma is identified. There is evidence that the ovarian mucinous tumours in PMP are on the surface of the ovary and secondarily derived from the associated appendiceal mucinous tumour.

Treatment options

There are three approaches in the management of  PMP:

  •  Watch and wait -  Monitor the situation closely
  • Surgery

Debulking -  the traditional surgical approach is to remove as much of the tumour as possible and generally includes removal of the uterus and ovaries and often the right colon and the omentum. Disease recurrence is almost inevitable due to residual and recurrent disease around the peritoneal cavity. Repeat debulking surgery may be possible on a number of occasions but each attempt becomes more difficult and dangerous. The small bowel becomes increasingly involved due to adhesions and eventually surgery is fraught with severe complications such as small bowel fistulae.

Cytoreductive surgery and peri-operative chemotherapy -  cytoreductive surgery refers to the aggressive removal or destruction of all visible tumours present throughout the peritoneal cavity. Peritonectomy procedures involving stripping the parietal peritoneum and resecting structures at fixed sites that contain adenomucinosis. This can be accomplished by removal or destruction of the tumour using a combination of surgical techniques that include organ resection and tumour destruction using electro-evaporation and argon beam coagulation. The operation may comprise a number of different procedures including:

  • right hemicolectomy, colectomy, removal of rectum and sigmoid (anterior resection)
  • greater omentectomy
  • splenectomy
  • cholecystectomy
  • lesser omentectomy
  • pelvic peritonectomy, which sometimes includes the rectum by anterior resection and removal of the ovaries and uterus
  • stripping of the peritoneum from the left hemidiaphragm
  • stripping of the peritoneum from the right hemidiaphragm
  • stripping of disease from the surface of the liver

The long-term results depend on the extent to which the tumour can be surgically removed. The smaller the residual tumour deposits the greater the chance it will respond to chemotherapy. Cytoreductive surgery is an extensive procedure that lasts on average more than ten hours. If complete tumour removal has been possible, intraperitoneal chemotherapy has been given and the tumour is at the benign end of the spectrum, 50-80% will have 10 year disease free survival.

After cytoreduction, chemotherapy is administered directly into the peritoneal cavity. The peritoneum-plasma barrier allows for a high concentration of drugs directly to the abdominal and pelvic surfaces where the tumour is located. The chemotherapy used is based on the drug's ability to produce a cytotoxic effect over a short time period (90 minutes in theatre) and to have an increased response with heat. The use of heated intra-operative intraperitoneal chemotherapy after complete dissection of adhesions and before anastomoses are completed allows optimal perfusion of the chemotherapy to the peritoneal surfaces and organs. Mitomycin C has a slow clearance from the peritoneal cavity. Pharmacokinetic studies of intra-operative intraperitoneal chemotherapy report an absorption of 75-90% of Mitomycin C within the first hour.

Heating chemotherapy not only improves drug distribution but also improves the drug cytotoxicity penetration into tissue compared to chemotherapy administration at room temperature.

 Chemotherapy

Evidence for the use of systemic chemotherapy in the management of PMP  has yet to be established. However, intestinal type chemotherapy sometimes has beneficial effects if the tumour has features of mucinous adenocarcinoma. A chemotherapy trial is currently underway for patients unsuitable for cytoreduction. The drugs involved are those used in HIPEC, after cytoreduction, and are known to be relatively well tolerated. Patients are monitored with regular follow up including blood tests and CT scans at a dedicated clinic at The Christie.

Post-operative mortality and morbidity

Complete cytoreduction carries a mortality risk of 3%-5%, which means 1/30 to 1/20 patients die as a direct result of surgical complications. The main complications are cardio-respiratory (lung infections and heart failure). There is also a risk of clots in the main leg veins, which can result in pulmonary embolus.

Surgery also has significant morbidity of around 30%. Approximately 20% (one in five) patients require further surgery to deal with the complications of the primary operation during the same admission. Approximately 20% of patients require a stoma. A permanent stoma is required if all or most of the colon has to be removed. A temporary stoma is usually used when the rectum has to be removed and the join, although appearing intact at the time of surgery, has a very high risk of leakage due to the particular position of the anastomosis, or join, and the fact that intraperitoneal chemotherapy is used. The temporary stoma is usually closed between three and six months after the primary operation.

The Peritoneal Tumour Service

Peritoneal Tumour Service is offered by a team that has specialist knowledge and skills in treating patients with tumours of the abdomen.

Documentation

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