VIDEO
CONTENT
QUIZ
MATERIALS
Introduction
Epidemiology
Etiology
Pathogenesis
Signs and Symptoms
Diagnosis
Staging
Differential Diagnosis
Treatment
Prevention
Prognosis
ICD
Research
Summary
Introduction to Pseudomyxoma Peritonei
Definition
Pseudomyxoma peritonei (PMP) is a rare condition characterized by:
- The presence of mucinous adenocarcinoma cells that produce abundant mucin or gelatinous ascites
- The accumulation of jelly-like mucin in the abdomen, often referred to as “jelly belly”
History
- First described by Werth in 1884
- Originally believed to originate from a perforated cystadenoma of the appendix
- Now known to arise from mucus-producing tumors in various sites like:
- Appendix
- Small and large bowel
- Stomach
- Pancreas
- Lung
- Breast
- Gallbladder
- Fallopian tubes
- Ovaries
Pathophysiology
- Classified as a borderline malignancy
- Rarely spreads through bloodstream or lymphatics
- Grows and spreads within the peritoneal cavity
Diagnosis
- Often an incidental finding during surgery or imaging for other causes
- Usually diagnosed at an advanced stage
Epidemiology
- Exact causes unknown
- More common in women than men
Treatment
- Main options are surgery and chemotherapy
- Choice depends on size of tumor and patient health status
Epidemiology of Pseudomyxoma Peritonei
Incidence and Prevalence
Pseudomyxoma peritonei (PMP) is a rare clinical condition with an estimated annual incidence of 1 to 4 cases per million people. Some studies suggest a slightly higher incidence rate of 2 to 4 cases per million people. A study in Europe estimated the incidence rate to be around 3.2 people per million each year. In China, the prevalence of PMP in 2016 was reported to be 2.47 per million person-year.
Age and Gender Distribution
PMP affects both males and females, with some studies suggesting a slightly higher prevalence in females. The average age at the time of diagnosis is around 53 years.
Survival Rates
The prognosis of PMP correlates closely with the histopathological classification of the tumor. The ten-year survival rate for patients with low-grade tumors is approximately 63%, compared to 40.1% for patients with high-grade tumors. It’s worth noting that 98.7% of recurrences occur within the first 10 years after diagnosis.
Geographic Distribution
The prevalence and incidence of PMP appear to be lower in mainland China than in European countries but are similar to those in Japan. In the UK, about 215 cases are diagnosed each year.
Etiology of Pseudomyxoma Peritonei
The exact cause of pseudomyxoma peritonei (PMP) is not known. There are no genetic, familial, or environmental factors known to cause this disorder. PMP generally originates from mucinous appendiceal tumors, which means that the initial site of the disease is usually the appendix, from where it spreads to other parts of the abdomen and pelvis. In some cases, PMP can also start in other organs such as the large bowel and ovary. The disease develops slowly, and it might be years before any symptoms appear. As a result, it has usually spread beyond the appendix before diagnosis.
Pathogenesis of Pseudomyxoma Peritonei
Initial Steps
The pathogenesis of pseudomyxoma peritonei (PMP) involves several steps. Initially, tumor cells originate from mucinous appendiceal tumors. These tumor cells then proliferate and produce mucin, which accumulates within the peritoneal cavity.
Mucinous Ascites and Peritoneal Implants
As the mucinous tumor cells continue to proliferate, they lead to the formation of mucinous ascites, which is the accumulation of mucin-containing fluid in the peritoneal cavity. This results in the characteristic “jelly belly” appearance. Additionally, peritoneal implants, omental cake, and possibly ovarian involvement may occur as the disease progresses.
Redistribution Phenomenon
The redistribution phenomenon is a key aspect of PMP pathogenesis. It refers to the intraperitoneal accumulation of mucus due to mucinous neoplasia. This accumulation can include mucinous ascites, peritoneal implants, omental cake, and ovarian involvement. The disease most commonly arises from appendiceal neoplasia and is considered a malignant condition.
Prognosis and Histopathological Classification
The prognosis of PMP is closely related to the histopathological classification of the tumor. Low-grade tumors have a better prognosis, with a ten-year survival rate of approximately 63%, compared to 40.1% for high-grade tumors.
Signs and Symptoms of Pseudomyxoma Peritonei
Pseudomyxoma peritonei (PMP) is a rare condition that may initially be asymptomatic or present with non-specific signs and symptoms. As the disease progresses, the following symptoms may appear:
- Abdominal or pelvic pain
- Gradual increase in waist size (jelly belly)
- Bloating
- Changes in bowel habits
- Hernia
- Loss of appetite
In more advanced stages, PMP may cause abdominal distension, ascites, bowel obstruction, and nutritional compromise.
Diagnosis of Pseudomyxoma Peritonei
Diagnosing pseudomyxoma peritonei (PMP) can be challenging due to its indolent nature and the fact that it often presents with non-specific symptoms. However, several diagnostic tools and procedures are commonly used to identify this condition.
Physical Examination
A physical examination is usually the first step in diagnosing PMP. The doctor may palpate the abdomen to check for any unusual lumps or swelling.
Blood Tests
Blood tests may be conducted to measure the levels of white and red blood cells, platelets, and tumor markers. Tumor markers are substances produced by cancer cells or by the body in response to cancer, and their presence in the blood can indicate the presence of a tumor.
Imaging:
- The diagnosis of Pseudomyxoma peritonei (PMP) is based on imaging techniques such as contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen.
- In CT, PMP appears as large hypodense or cystic masses with an intensity of < 20 Hounsfield Units (HU), covering the peritoneum and compressing visceral organs.
- In MRI, signal intensities vary depending on the mucin concentration. PMP typically appears hypointense in T1-weighted and hyperintense in T2-weighted images.
- Fat-suppression sequences allow the detection of cellular components within the mucin, and Diffusion-weighted imaging (DWI) sequences increase sensitivity and specificity in detecting early-stage PMP.
- The determination of the PCI can also be done through imaging by dividing the abdomen into 9 regions, supplemented by the categorization of the small intestine on the remaining slice. The morphological determination of PCI through imaging correlates well with intraoperative evaluation.
Biopsy
A biopsy, often taken during a laparoscopy or laparotomy, is crucial for confirming the diagnosis of PMP. When suspicious lesions are encountered, generous biopsies are taken, and the appendix is removed if accessible. The samples are then sent to a pathology lab for examination under a microscope to confirm the presence of PMP.
Staging
Once PMP is diagnosed, it’s important to determine the extent or stage of the disease. This can help guide treatment decisions. Staging usually involves further imaging studies to determine whether the disease has spread and, if so, how far.It’s important to note that the diagnosis and treatment plan should be confirmed by a multidisciplinary team of specialists, including surgeons, oncologists, and radiologists, to ensure the best possible outcome for the patient.
Peritoneal Cancer Index (PCI):
- The Peritoneal Cancer Index (PCI) was developed to allow for a quantitative macroscopic assessment of the disease and its distribution within the abdominal cavity.
- The parietal peritoneum is divided into 9 regions, and an additional 4 regions are added for the small intestine.
- Points ranging from 0 to 3 are assigned based on the size of lesions (size up to 0.5 cm = 1 point, 0.5–5 cm = 2 points, confluent lesions and > 5 cm = 3 points).
- The PCI value ranges from 0 to 39.
- The Completeness of Cytoreduction Score (CC) complements the PCI and indicates the extent of disease remaining after resection (CC-0: no macroscopic residues, CC-1: < 2.5 mm, CC-2: tumor nodules between 2.5 mm and 2.5 cm, CC-3: tumor nodules over 2.5 cm).
- CC-0 and CC-1 are considered complete cytoreduction, as lesions up to 2.5 mm can be treated with subsequent HIPEC therapy.
Staging of Pseudomyxoma Peritonei
Staging of pseudomyxoma peritonei (PMP) is crucial for determining the appropriate treatment approach. The staging system is based on the extent of the disease and the histopathological classification of the tumor.
Histopathological Classification
PMP can be classified as low-grade or high-grade mucinous carcinomatosis peritonei. This distinction correlates with the clinical outcome.
- Low-grade tumors: These tumors are less aggressive and have a better prognosis.
- High-grade tumors: These tumors are more aggressive and have a poorer prognosis.
Staging System
The staging system for PMP is based on the extent of the disease, which is determined through imaging studies and biopsy. The system includes the following stages:
- Stage I: The disease is confined to the appendix.
- Stage II: The disease has spread to the peritoneum but is still localized.
- Stage III: The disease has spread extensively within the peritoneum.
- Stage IV: The disease has spread to distant organs or tissues.
Differential Diagnosis of PMP:
- Ascites from Other Origins:
- Conditions such as cirrhosis and congestive heart failure can lead to the accumulation of fluid (ascites) in the peritoneal cavity, resulting in symptoms similar to PMP, including abdominal distension and discomfort.
- Ruptured Mucinous Cystadenomas:
- Rupture of mucinous cystadenomas originating from the appendix or ovary can release mucin into the peritoneal cavity, mimicking the presentation of PMP.
- Endometriosis:
- Endometriosis, characterized by the growth of uterine-like tissue outside the uterus, can sometimes lead to the formation of cysts filled with a thick, brown, sticky fluid, which may be mistaken for mucinous ascites seen in PMP.
- Peritoneal Carcinomatosis:
- Peritoneal carcinomatosis occurs when cancer spreads to the peritoneal surfaces. It can manifest with symptoms and imaging findings resembling PMP, including ascites and peritoneal nodules.
- Peritoneal Sarcomatosis:
- Peritoneal sarcomatosis is a rare condition where sarcoma, a cancer originating in tissues like bone or muscle, spreads to the peritoneum, potentially presenting with symptoms similar to PMP.
- Tuberculosis Peritonitis:
- Tuberculosis peritonitis is a form of tuberculosis affecting the peritoneum. It can lead to ascites and abdominal pain, which may resemble PMP symptoms.
- Goblet Cell Carcinoid Tumor:
- Goblet cell carcinoid tumors, a rare type of tumor that can develop in the appendix, can produce mucin, leading to a presentation similar to PMP.
- Myxoid Neoplasms:
- Myxoid neoplasms are a group of tumors characterized by mucin-like tissue. They can occur in various parts of the body and may release mucin into the peritoneal cavity, mimicking PMP.
Treatment of Pseudomyxoma Peritonei (PMP):
- Watch and Wait (Active Surveillance):
- For small and slow-growing PMP, doctors may choose to closely monitor the patient without immediate treatment.
- This involves regular check-ups with blood tests and scans.
- Surgery (Debulking Surgery):
- Surgery is a central part of PMP treatment with the goal of removing as much cancer as possible.
- Cytoreductive surgery (CRS) is a specific surgical approach used, which involves removing all tumor tissues from the parietal and visceral peritoneum.
- Small cancer deposits on the visceral peritoneum may be individually electroevaporated, and large tumor nodules in the small bowel may be resected.
- All visible tumors are removed to maximize the benefits of peri-operative intraperitoneal chemotherapy.
- Chemotherapy:
- Chemotherapy can be administered systemically or directly into the abdomen (intraperitoneal chemotherapy).
- In combination with surgery, intraperitoneal chemotherapy is often heated (hyperthermic intraperitoneal chemotherapy or HIPEC) to enhance its effectiveness.
- Specialist Centers:
- Due to the rarity and complexity of PMP, treatment is often carried out in specialized centers with expertise in managing this condition.
- Research and Future Directions:
- Ongoing research aims to improve PMP treatments.
- Areas of research include refining surgical techniques, optimizing chemotherapy regimens, and exploring new treatment modalities.
- Palliative Care:
- For patients with advanced PMP that cannot be cured, palliative care can help manage symptoms and slow down disease progression.
Surgical Resection Techniques
Surgical resection techniques for cytoreductive surgery, especially peritonectomy, were developed approximately 30 years ago. Due to the mucinous gel-like consistency of tissue in Pseudomyxoma Peritonei (PMP), specific techniques are necessary to ensure the complete removal of mucin. The following aspects should be considered:
- Extraperitoneal Parietal Peritonectomy of the Abdominal Wall: In this technique, except for a small window to assess the spread of PMP, the parietal peritoneum remains intact. It is initially mobilized from the anterior abdominal wall.
- Removal of Visceral Peritoneum from the Bladder: This involves continuing extraperitoneal dissection up to the cervix uteri or, analogously, to the seminal vesicles.
- Extraperitoneal Pelvic Peritonectomy with En-Block Resection of the Rectum, Uterus, Ovaries, and Douglas Space Peritoneum: Particularly through extraperitoneal dissection of the rectum, adequate length for a deep anastomosis can usually be achieved.
- Stripping of the Bursa Omentalis, Resection of the Omentum Minus, Peritonectomy of the Ligamentum Hepatoduodenale, Cholecystectomy, and Deep Resection of the Ligamentum Teres Hepatis: These procedures are essential for complete cytoreduction.
HIPEC (Hyperthermic Intraperitoneal Chemotherapy)
The use of HIPEC following resection is now an accepted standard in the treatment of PMP. HIPEC penetrates tissue to a depth of approximately 2.5 mm, and a CC-1 (Completeness of Cytoreduction Score 1) situation is considered complete cytoreduction.
Various therapeutic regimens with different chemotherapeutic agents have been used over the years. Currently, evidence suggests that the original form of HIPEC with Mitomycin C is the most effective therapeutic regimen for PMP. There are different protocols for Mitomycin-C-based HIPEC regimes.
A promising approach could be the use of Bromelain and Acetylcysteine therapy for PMP. The combination of these substances results in significant mucolytic effects, as demonstrated in numerous experimental studies. In a clinical phase-1 study, Bromelain and Acetylcysteine were percutaneously injected into the mucus of patients who were not suitable for CRS and HIPEC, and the mucus was subsequently aspirated. This demonstrated the feasibility of mucolysis.
Prevention of Pseudomyxoma Peritonei (PMP):
- Regular Follow-ups:
- Patients who have had a mucinous neoplasm (MN) of the appendix should undergo systematic follow-up to detect PMP as early as possible.
- This is particularly important for patients with a perforated MN, as they may be at higher risk of developing PMP.
- Prophylactic Hyperthermic Intraperitoneal Chemotherapy (HIPEC):
- In some cases, prophylactic HIPEC may be proposed to selected patients to prevent the occurrence of PMP.
- This is especially considered for patients who have had a mucinous neoplasm of the appendix, a known precursor of PMP.
- Peritoneal Lavage:
- The combined use of intraperitoneal lavage with dextrose 5% and water, along with an aggressive surgical approach, has been suggested as a method to prevent the reaccumulation of PMP.
- Surgical Removal of Mucinous Lesions:
- Surgical removal of mucinous lesions, particularly in the appendix, can prevent potential rupture in the future, which could lead to PMP.
Prognosis of Pseudomyxoma Peritonei (PMP):
- Histopathological Classification:
- The prognosis of PMP depends on the histopathological classification of the tumor.
- Patients with low-grade tumors tend to have a better prognosis, with a 5-year survival rate of approximately 63%.
- High-grade tumors have a lower 5-year survival rate, around 40.1%.
- Extent of the Disease:
- The extent of the disease also plays a crucial role in prognosis.
- PMP is an indolent (slow-growing) disease, and long-term survival up to 20 years has been reported.
- Treatment Approach:
- The choice of treatment can significantly impact prognosis.
- Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is one treatment approach that can influence outcomes.
- Approximately half of patients treated with CRS and HIPEC do not experience recurrence.
- Overall Health and Response to Treatment:
- Individual factors such as the patient’s overall health and how they respond to treatment can also affect prognosis.
- Response to treatment and the ability to manage potential complications are important considerations.
- C78.0 – Secondary malignant neoplasm of the lung: This code is used to classify metastases of malignant tumors in the lung.
- C78.1 – Secondary malignant neoplasm of the mediastinum: This code refers to metastases in the tissues of the mediastinum, which is located in the chest area between the lungs.
- C78.2 – Secondary malignant neoplasm of the pleura: This code covers metastases that occur in the pleura, which is the tissue surrounding the lungs.
- C78.3 – Secondary malignant neoplasm of other and unspecified respiratory organs: This code includes metastases in other respiratory organs that are not specifically identified.
- C78.4 – Secondary malignant neoplasm of the small intestine: It relates to metastases in the small intestine.
- C78.5 – Secondary malignant neoplasm of the colon and rectum: This code pertains to metastases in the colon and rectum.
- C78.6 – Secondary malignant neoplasm of the retroperitoneum and peritoneum: It involves metastases occurring in the retroperitoneum (tissue behind the abdominal cavity) and the peritoneum (abdominal lining).
- C78.7 – Secondary malignant neoplasm of the liver and intrahepatic bile ducts: This code is used to classify metastases in the liver and its intrahepatic bile ducts.
- C78.8 – Secondary malignant neoplasm of other and unspecified digestive organs: This code covers metastases in other digestive organs that are not specifically identified.
Pseudomyxoma Peritonei (PMP):
- Definition: PMP is an exceptionally rare malignant growth characterized by the progressive accumulation of mucinous (mucus-secreting) tumor cells within the abdomen and pelvis.
- Incidence: PMP is a very rare disorder, with an estimated incidence of approximately 2 cases per million individuals. It affects both males and females equally.
- Origins: PMP generally originates from mucinous tumors, most commonly from the appendix.
- Symptoms: The most common symptoms in individuals with PMP are a result of the progressive accumulation of mucinous tumors within the abdominal and pelvic regions. These symptoms include:
- Increasing abdominal size, often described as “jelly belly.”
- Abdominal discomfort due to pressure from the growing tumors.
- Treatment: Treatment of PMP typically involves extensive surgical procedures aimed at removing the mucinous tumors and mucin from the abdomen and pelvis. These surgeries are complex and often require specialized medical teams.
- Prognosis: The prognosis for individuals with PMP can vary depending on the extent of the disease and the success of surgical interventions. Early diagnosis and appropriate treatment are crucial for improving outcomes.