Routine examination of ascites includes testing for color, transparency, cell count, and specific gravity. 1) Color: MA usually appears yellow or bloody, mostly yellow, due to the presence of bilirubin or components of bile. Cancer cells invading the liver or biliary system may lead to bile leakage or accumulation, resulting in yellow ascites. In some cases, MA may also appear bloody, which may be due to cancer cells invading blood vessels in the abdominal cavity, causing blood to leak into the ascites; bloody ascites may also be related to vascular rupture and bleeding caused by malignant tumor infiltration. 2) Specific gravity: The specific gravity of MA is often greater than 1.018. However, it cannot be distinguished from infectious ascites, and approximately 40% of MA has a specific gravity <1.016. 3) Cell count: The number of red blood cells in MA usually exceeds 100,000/μL. The ratio of red blood cells to white blood cells usually exceeds 10:1. When this occurs, the first thing to suspect is MA caused by liver cancer rupture, peritoneal metastasis, or other cancer. However, the sensitivity and specificity of these indicators are low (24) and are influenced by various subjective and objective interference factors.

The biochemical examination of ascites includes the detection of indicators such as protein, ferritin, serum ascitic albumin gradient, fibronectin, lactate dehydrogenase concentration, glucose, ascitic pH, cholesterol, lysozyme, and adenosine deaminase. 1) Protein: MA usually contains high levels of protein, often above 30g/L, and the ratio of ascites to serum albumin is mostly greater than 0.5. 2) Ferritin: Exudative ascites, such as >500 μg/L or ferritin ascites/serum ratio >1.0, often indicates MA. 3) Serum ascites albumin gradient (SAAG): The gradient of MA is usually less than 1.1 g/dL (25), and the portal hypertension secondary to liver metastasis may cause SAAG to be greater than 1.1 g/dL (26). 4) Fibronectin (FN): It is a high molecular weight glycoprotein that exists in the extracellular space of human tissues. FN has a high concentration in MA, often >75 mL/L. 5) Lactate dehydrogenase (LDH): LDH >3.34 in exudative ascites μmol (L s), ascites/serum LDH ratio >0.6, often indicates cancer or infection. If LDH >8.35 μmol (L s) and if the ratio of ascites to serum is greater than 1.0, it highly indicates MA (27). 6) Glucose: Due to the consumption of cancer cells, MA may present low concentrations of glucose levels, often <2.8 mmol/L (28). 7) Cholesterol (TC): Among the lipids in ascites, the determination of cholesterol (TC) is the most valuable for distinguishing between benign and MA. When the TC in ascites is greater than 1.24 mmol/L, it strongly suggests the possibility of cancer (29). 8) Lysozyme: Cancer cells do not contain lysosomes and do not produce lysozyme. Therefore, when the level of lysozyme in exudative or inflammatory ascites does not increase (below 23 mg/L) (30), this usually indicates MA. 9) Adenosine deaminase (ADA): It plays an important role in activating and promoting the differentiation and proliferation of lymphocytes to enhance the body’s immune function. Studies have found that (30) ADA levels in ascites of cancer patients are significantly reduced. The area below the ROC curve (AUC) for ADA diagnosis of benign and MA is 0.797 (30), with good accuracy.

At present, the gold standard for diagnosing MA in clinical practice is still to search for shed cancer cells in the ascites, and collecting 500 mL of ascites is sufficient for cytological evaluation. However, due to the atypical cell morphology and the influence of sample sampling techniques, although this method has high specificity, its sensitivity is only 50%–60%, and the true positive rate is only 30%–50% (31), with a high false negative rate.

Tumor markers (TMs) are a type of substance secreted and released by tumor cells or their related tissues, which can reflect the presence and growth of tumors and help identify and indicate the nature of tumors. The common TMs currently used for diagnosing benign and MA include carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), etc. CEA is a broad-spectrum tumor marker when its level is >15 μg/L (32), which prompts MA. In ascites caused by primary liver cancer metastasis, AFP levels are commonly elevated (33); CA19-9 is highly correlated with pancreatic cancer, gallbladder cancer, colorectal cancer, and gastric cancer (32). In ovarian cancer, pancreatic cancer, lung cancer, or breast cancer, the level of CA125 is often increased (34). However, the sensitivity of AFP, CEA, and CA19-9 to the diagnosis of MA is 28.5%, 38.0%, and 19.0%, respectively (35). Therefore, their application in clinical diagnosis is limited. The study of Liu et al. (36) showed that TM in MA has better diagnostic performance than in serum, and the combination of TM and cytological examination increased the diagnostic rate of the latter by 37%. Therefore, in clinical practice, joint testing is usually performed, and when combined testing is performed (36), although there is no significant difference in sensitivity, specificity can be significantly improved.

X-ray plain films can be used to assist in the diagnosis of ascites. Pertinent positive findings include the following (35): 1) hepatic angle sign (the absence of the lower edge of the right lateral hepatic angle), 2) medial displacement of the lateral edge of the liver, 3) pelvic fluid, 4) intestinal loops in an aggregated state, 5) intestinal loops in a separated state, and 6) a blurry abdomen throughout the body. However, similar to physical examination, X-ray examination generally produces positive results only in the presence of a large amount of ascites and usually has low sensitivity and specificity.

1) CT attenuation value of ascites (40): MA is generally an exudate, containing more protein, and the CT value of ascites density is often greater than 20 Hu. 2) Peritoneal structure (41): The peritoneum is often nodular or irregularly thickened. The density of the mesentery and greater omentum increases, appearing as a cake-shaped or patchy thickening, with significant enhancement after being enhanced. 3) Intestinal bondage sign (41): It shows aggregation and constriction, often due to adhesion caused by lesion metastasis. 4) Omental sac ascites (42): The ascites is located in the large and small omental sacs, and there is a sign of omental sac effusion. 5) Ascites ADC value (43): MA is rich in protein and chylomicrons and has a high viscosity, so the ADC value is usually lower than that of benign ascites. 6) T1- and T2-weighted images show medium to high signal intensity. CT and MRI can not only directly detect ascites but also help locate the primary lesion; clarify the presence of enlarged lymph nodes and abdominal and pelvic masses, as well as the condition of abdominal organs such as the liver and spleen (44); and make a comprehensive evaluation.

Ultrasound is of great significance for the detection and quantification of body cavity effusion, with the advantages of repeatability, non-invasiveness, and dynamic observation (45). It is currently the most sensitive imaging diagnostic method for body cavity effusion. Ultrasound can detect a very small amount of fluid accumulation in the body cavity. Generally, there is approximately 100 mL of fluid in the abdominal cavity that can be detected (46). MA can be seen with densely distributed large punctate echoes, some of which can be fragmented (diameter > 3 mm) (47).

VEGF is a key proangiogenic cytokine that promotes uncontrolled tumor growth and participates in the production of MA. Abdel Razik et al. (48) conducted a prospective study on 315 patients with benign MA, using enzyme-linked immunosorbent assay to evaluate the levels of VEGF in serum and ascites. They found that the VEGF levels in the MA group were significantly higher than those in the benign ascites group, with detection sensitivity and specificity of 94.9% and 89.5%, respectively.

MMPs are secreted by tumor cells, which break down the tissue matrix during tumor spread, destroy the basement membrane structure, and increase vascular permeability, promoting MA growth (49). Zhang Yanli et al. (50) retrospectively analyzed ascites samples from 59 hospitalized patients. They found that the MMP-3 expression level in the MA group (195.75 + 46.81 ng/mL) was higher than that in the benign ascites group (93.87 + 20.65 ng/mL), with P < 0.01.

Telomerase is an enzyme responsible for the elongation of telomeres in cells, which activates and promotes the division and proliferation of tumor cells (51). Park Es et al. (52) studied 19 patients with gastrointestinal origin MA and found that the positive rate of detecting telomerase activity was significantly higher than that of benign ascites. The sensitivity range of telomerase activity in MA was 78%–84%, which was higher than that of ascites cytology. Therefore, it can be used as a useful auxiliary diagnostic method.

TGF-β1 belongs to the small molecule peptide class and is a group of bioactive substances with cellular regulatory functions, which are highly expressed in tumors (53). In clinical practice, there are certain difficulties in distinguishing between ascites caused by tuberculous peritonitis and MA. He Kun et al. (54) found TGF-β1 in the ascite group of liver cancer patients by grouping and testing 82 patients with MA. The expression level was significantly higher than that of the group with tuberculous peritonitis, indicating TGF-β. The differential diagnosis of the two has a certain value.

For patients with ineffective diuretic treatment, abdominal puncture drainage is the most commonly used method for treating MA symptoms. A physician practice survey (70) reported that 98% of doctors have used puncture surgery, and 89% of doctors believe it is effective. A total of 90% of patients experience rapid but brief relief of symptoms such as bloating, abdominal pain, and difficulty breathing. However, the effect is often short-lived, and some patients may even experience symptom recurrence within 72 h (20). Therefore, in order to control symptoms, patients often need to undergo frequent repeated punctures with an average interval of 10.4 days (56). Becker et al. (1) conducted a multicenter prospective observational study on MA patients admitted to palliative care units, and the results showed that 81% of patients who received puncture treatment, as evaluated by the Numerical Rating Scale (NRS), experienced significant improvement in abdominal distension symptoms. It is worth noting that more than half of patients had to undergo two or more puncture procedures during hospitalization. Repeated puncture and drainage of MA can be accompanied by a series of risks and complications, including (71) decreased effective circulating blood volume, hypotension, pain and even perforation during the puncture process, secondary peritonitis, electrolyte imbalance such as hyponatremia, renal dysfunction, and fluid balance problems caused by hypoalbuminemia, as well as serious complications such as infection and bleeding. Over time, the efficacy of the puncture procedure may gradually weaken, while the risk of complications continues to increase, bringing additional physical and psychological burdens to patients.

When abdominal puncture drainage leads to serious electrolyte disorders and other complications, or when it is impossible to control fluid increase through continuous puncture, an indwelling peritoneal catheter for abdominal drainage is usually considered. One potential advantage of indwelling catheters is that they can also be used for intravenous infusion, chemotherapy, or targeted therapy. Multiple indwelling catheters have been used for MA management, including non-tunnel and tunnel pleural catheters, tunnel Tenckhoff catheters, non-tunnel Foley self-retaining catheters, scope-type circulating drainage catheters, tunnel and non-tunnel peritoneal catheters, and tunnel peritoneal ports. However, the service life of drainage tubes is limited by functional failures and infections, and catheterization complications include sepsis, cellulitis at the catheter site, leakage at the catheter site, catheter occlusion, and fatal hypotension (68). Due to the high incidence of non-tunnel catheter-related infections and peritonitis, it is usually only recommended for patients with short life expectancy patients with short life expectancy).

For primary cancer, selecting sensitive chemotherapy drugs can control the tumor and reduce MA. For ovarian cancer, breast cancer, lymphoma, and other cancers that are more sensitive to chemotherapy, systematic treatment is generally used, which may achieve good results. The main reference for the regimen is the systemic chemotherapy guidelines. For example, for ovarian cancer (72), the CAP (cyclophosphamide, adriamycin, cisplatin) regimen or paclitaxel combined with carboplatin can be used; the CHOP (cyclophosphamide, vincristine, adriamycin, prednisone) regimen is chosen for lymphoma (73). For breast cancer (74), CAF (cyclophosphamide, adriamycin, 5-fluorouracil) or combination chemotherapy containing taxus was used. When patients experience moderate to large amounts of MA accompanied by symptoms such as bloating, oliguria, and poor appetite, it is necessary first to alleviate the related symptoms caused by ascites and then undergo systematic chemotherapy after the general situation improves. However, patients with advanced cancer often struggle to tolerate systemic chemotherapy due to physical weakness. According to a research report (12), for cancer patients with MA who cannot undergo tumor resection, the 5-year survival rate after receiving systemic chemotherapy does not exceed 10%.

Intraperitoneal chemotherapy refers to injecting chemotherapy drugs into the abdominal cavity. This method can increase the concentration of drugs in the local area of the abdominal cavity and improve drug permeability and cellular uptake, thereby enhancing the direct cytotoxicity of chemotherapy drugs. The peritoneal barrier and liver first-pass effect limit the entry of chemotherapy drugs into the systemic circulation, mainly through the slow absorption of drugs in the portal vein. This method can reduce the drug concentration in other parts of the body, especially in the bone marrow. The systemic toxic side effects of intraperitoneal chemotherapy are lighter compared to other treatment methods (75).

Since VEGF is a key factor that triggers ascites, injecting VEGF monoclonal antibodies or VEGF inhibitors into the abdominal cavity, such as bevacizumab and ranibizumab, can be used for the treatment of MA and has achieved certain therapeutic effects. In a clinical study conducted by Zhou et al. (94), in addition to receiving cisplatin intraperitoneal infusion therapy, the observation group also received bevacizumab intraperitoneal infusion therapy for MA. In contrast, the control group only received cisplatin intraperitoneal infusion. The results showed that the observation group’s MA volume and average urine volume were significantly improved, and the difference was statistically significant compared to the control group. Chen Peng et al. (95) used sequential intraperitoneal infusion of endostatin (endostatin) combined with docetaxel and intraperitoneal infusion of docetaxel alone to treat MA. They found that the total effective rate of the endostatin combined with the docetaxel group was 96.55%, and the adverse reaction rate was 6.90%. These data were significantly better than those of the docetaxel alone group.

MMPs are an enzyme family overexpressed in multiple types of cancer. Intraperitoneal injection of MMP inhibitors can effectively slow down tumor growth, metastatic spread, and the generation of MA (50).

Interleukin-2 (IL-2), interferon (96), BCG vaccine (97), tumor necrosis factor-alpha (TNF-α) and streptococcal preparation (OK-432), highly agglutinative staphylococcin (HAS) (98), Nocardia rubra cell wall skeleton (99), Corynebacterium parvum (100), and somatostatin (101) can be used alone or in combination with other drugs for the treatment of MA. The mechanism by which these modulators work is related to their activation of the immune system, making cancer cells more sensitive to the body’s defense mechanisms or the effects of anticancer drugs. Guo Nannan et al. (102) used a combination of snake venom hemagglutinin and IL-2 to treat MA, and the therapeutic effect was significantly better than that of the snake venom hemagglutinin combined with the cisplatin group while significantly improving the quality of life of patients. Qin Shukui et al. (103) reported the use of recombinant human TNF-α for single-drug intracavitary infusion therapy for MA. In 302 MA patients, the objective response rate reached 46.03%, and the disease control rate was as high as 97.27%. Although biological agents have definite therapeutic effects in treating ascites, some researchers have pointed out that the method of infusing inflammatory biological agents into the abdominal cavity has limited effectiveness and instead increases the risk of abdominal fibrosis. Clinically, this often leads to intestinal obstruction, which directly leads to a sharp decline in patients’ quality of life.

A peritoneal venous shunt (PVS) is a tubular system of one-way valves that can open under specific pressure, allowing fluid to flow from the peritoneal cavity to the superior vena cava. PVS not only helps alleviate symptoms but also has significant advantages over other treatment methods in saving electrolytes and proteins, maintaining fluid balance and avoiding repeated puncture surgeries (104). Due to its purpose of relieving symptoms (104), PVS is not suitable for patients with short life expectancy (<30 days). Its complications are quite extensive, including postoperative fever, edema, gastrointestinal bleeding, sepsis, tachycardia, ascites leakage, PVS dysfunction or mechanical occlusion, disseminated intravascular coagulation, acute heart failure, and infection. Tumor cells injected into the central venous system may also cause a large number of early metastases. These factors all limit the application of PVS, and its current clinical use is not widespread.

Transjugular intrahepatic portosystemic shunt (TIPS) technology, which establishes a portosystemic shunt in the liver parenchyma between the hepatic vein and portal vein, can significantly reduce portal vein resistance structurally. It has certain therapeutic effects on liver cancer with portal hypertension and refractory ascites and can accelerate the discharge of abdominal fluid. In TIPS surgery, there may be a risk of tumor rupture or bleeding when the puncture needle or shunt passes through the tumor. Hong Dong and his team (105) retrospectively analyzed the clinical data of 13 patients with bleeding and ascites caused by hepatocellular carcinoma and portal hypertension. The results showed that the incidence of MA before and after TIPS treatment was 84.6% (11/13) and 7.7% (1/13), respectively. This indicates that TIPS can effectively control MA, bleeding, etc., which helps patients better adapt to subsequent antitumor treatment and achieve a good quality of life.

After abdominal exploration, visible peritoneal tumor tissue is removed and reduced to the greatest extent possible, retaining only residual lesions under the microscope. Subsequently, heated chemotherapy drugs were used for intraperitoneal infusion to maximize the elimination of residual cancer cells in the abdominal cavity. Cell reduction surgery (CRS) is most commonly combined with HIPEC. In a meta-analysis on the application of CRS combined with HIPEC in primary ovarian cancer (106), a significant improvement was reported in the 5-year overall survival (OS) (393 cases, hazard ratio = 0.77; 95% confidence interval 0.67–0.90; P = 0.001) and disease-free survival (DFS) (hazard ratio = 0.60; 95%; confidence interval 0.41–0.87; P = 0.008) after treatment.

Released from radioactive isotopes, β radiation can kill malignant tumor cells at short distances. In clinical practice, 32P is the most commonly used. Radionuclides have shown better efficacy in the treatment of MA patients with positive exfoliated cells in ascites, diffuse metastasis to the dry peritoneum, or implantation. According to literature reports (107), the highest effective rate of radioactive nuclides in treating MA can reach 80%, and the resolution time of some ascites can even reach up to 6 months. The main complications include radiation-induced enteritis, intestinal obstruction, and intestinal infarction.

Catumaxomab (108) is a three-functional, non-humanized mouse/rat monoclonal antibody that targets the epithelial cell adhesion molecule (EpCAM) on T cells. In 70%–100% of MA cases, tumor cells commonly express EpCAM (109), and injection of cetuximab can directly reduce the number of circulating tumor cells in the peritoneal cavity, thereby reducing the production of MA. In a phase II/III clinical trial (110), catumaxomab was used to treat symptomatic MA patients with EpCAM-positive tumor recurrence. Compared with puncture alone, the addition of cetuximab significantly prolonged puncture-free survival.

Peritoneal metastasis (PM) is a persistent challenge in the treatment of MA. A high-flow gas-based heat shock program that combines hyperthermia and dehydration (dehydrating the peritoneal cavity, which induces peritoneal drying and cancer cell necrosis on the peritoneal surface) has become a new method for treating PM.

Diakun A and other scholars (90) have innovatively explored the potential of gas-based intraperitoneal hyperthermia (GIH) and pointed out that, without causing harmful increases in the body’s core temperature, GIH can be safely implemented within the range of 48°C–50°C by utilizing the low specific heat capacity of gaseous substances (91), effectively inducing a decrease in HT-29 colon cancer cell viability and an increase in cytotoxicity. This study is the first to evaluate the therapeutic potential of in-vivo dehydration, hyperthermia, and their combination in animal models (pigs). Using diagnostic laparoscopic techniques, high-flow airflow treatment was applied at specific temperatures (48°C, 49°C, 50°C) to measure cell toxicity and viability at different time intervals. The results showed that both dehydration and hyperthermia had cytotoxicity on HT-29 cells, and the effect of dehydration on cell viability was significantly increased when combined with hyperthermia (P < 0.01) (92).

In addition, the study of Khosrawipour C et al. (93) further expanded the boundaries of the combined application of dehydration and chemotherapy under high-temperature conditions. They simulated a high-temperature environment to partially dehydrate HT-29 colon cancer cells, followed by chemotherapy intervention with oxaliplatin or doxorubicin. They found that compared to chemotherapy alone, this combination therapy significantly improved the overall cytotoxicity of colon cancer cells. This discovery not only confirms the superiority of the synergistic effect of high-temperature dehydration and chemotherapy but also provides strong scientific support for the comprehensive treatment strategy of PM.

Nucleic acid treatments (111) including the application of messenger RNA (mRNA), small interfering RNA (siRNA), and microRNA (miRNA) work by precisely regulating the expression and silencing of specific genes or gene products closely related to cancer growth and progression, achieving precise targeted therapy for cancer.