Ascites is a common clinical sign, either as a local manifestation caused by systemic disease or as a result of peritoneal disease itself, and is called ascites when the free fluid in the abdominal cavity exceeds 200 ml. The etiology of ascites is diverse; in Western countries, about 80% of patients with ascites have chronic liver disease as the cause, with malignancy, heart failure, tuberculosis, etc. in second place. In addition to liver diseases such as cirrhosis, cardiac origin such as cardiac insufficiency, and nephrogenic factors such as nephrotic syndrome, obstetrical and gynecological diseases are not uncommon for female patients. Therefore, in the diagnosis of the etiology of female patients with ascites, gynecologic diseases that can produce ascites need to be identified in particular.
1. Diagnostic methods for the etiology of ascites
1.1 History taking and physical examination For each female patient with ascites, the initial evaluation should begin with a thorough history taking and physical examination. A history of alcohol abuse, liver disease, renal disease, hypothyroidism, acute pancreatitis, biliary tract, immune disorders, exposure to tuberculosis, and malignancy should be asked. Varices of the abdominal wall, jaundice, liver palms, and spider nevi are meaningful signs of liver disease; cardiogenic ascites is mainly a manifestation of right heart failure and includes increased central venous pressure, hepatomegaly, and possible valvular disease; if combined with fever, one should be alert for infections such as tuberculosis or spontaneous peritonitis; enlarged lymph nodes are usually seen in malignant diseases or chronic infections. In addition, special emphasis should be placed on gynecologic examination. Irregular, poorly mobile solid masses and palpable nodules without tenderness in the rectal fossa of the uterus suggest the possibility of gynecologic malignancy. These clinical data are a strong basis and an important clue for the differential diagnosis of ascites, and help to make a rapid and correct preliminary judgment on the etiology of ascites.
2.2 Imaging examinations such as ultrasound, CT, MRI and other imaging examinations can not only determine the existence and amount of ascites, but also search for the primary lesion of ascites and provide a basis for the diagnosis of the cause of ascites. In patients suspected of tuberculosis, chest X-ray can detect 30% to 50% of the tuberculous lesions in the chest. In patients with suspected cardiogenic ascites, chest radiographs and echocardiography are also useful for diagnosis. In patients with sepsis, ascites arising from intra-abdominal infection due to suspected visceral perforation is excluded by radiographs indicating the presence or absence of subseptal free gas.
2.3 Ascites analysis should routinely be performed in all patients with new, symptomatic ascites as an important first step in determining the cause of ascites. Laparotomy is a quick and easy way to obtain an ascites specimen. The aspirated ascites can be analyzed for ascites cell count, total protein/albumin concentration, culture, cytology, and immunologic examination.
The identification of benign and malignant ascites is not only valuable in identifying the cause and evaluating the prognosis, but is also essential in determining the principles and protocols of treatment. Cytologic examination of ascites is a quick, reliable and economical method to confirm the diagnosis of malignant ascites. Malignant cells are shed into ascites and are easily detected. A large number of ascites with few or no shed cells, destruction of tumor cells, and well differentiated tumor cells can lead to false negative results, so the positive rate of cytology examination is low, only 40%~60%. In addition, it is sometimes difficult to distinguish tumor cells from inflammatory cells and phagocytes, and the false-positive rate is 8%~38%.
2.4 Peritoneal puncture biopsy Peritoneal puncture biopsy is a special means of diagnosing unexplained ascites carried out at home and abroad in recent years. In cases of ascites due to suspected peritoneal tumors or peritoneal metastases, peritoneal biopsy can achieve a diagnostic rate of 25%-50%, and the sensitivity of blind percutaneous peritoneal biopsy for the diagnosis of tuberculosis is 65-85% [1].
2.5 Laparoscopy is the best option for patients with ascites whose etiology has not been confirmed clinically by any of the above means and has been confirmed by many large-scale studies. Laparoscopy has advantages in the diagnosis of ascites that cannot be matched by other means of examination. First, it can visualize and directly see the abdominal cavity, probing the pelvic organs, the anterior abdominal wall peritoneum, 75% of the septal surface, 2/3 of the liver surface, the gallbladder, the appendix, the plasma membrane surface of the intestinal duct, part of the duodenal plasma membrane and the anterior wall of the stomach, the tail of the pancreatic body and the greater omentum, and can detect microscopic lesions of 1 to 2 mm in diameter that cannot be detected by ultrasound, CT or MRI. The initial diagnosis can be made by the characteristic laparoscopic performance. Secondly, it can perform pathological examination of suspicious tissues under direct vision and accurately, avoiding the disadvantages of blindness and low positive rate of laparoscopic peritoneal biopsy, ascites for tumor cells and ascites bacterial culture, and improving the diagnostic rate. The confirmation rate of laparoscopy is as high as 82%~96%. In addition, laparoscopy not only can avoid normal organ damage, but also can perform ligation and hemostasis under laparoscopy once bleeding and other complications are found at the lesion site, which has the characteristics of high safety, low mortality and complication rate. However, there are still certain limitations, after all, it is an invasive operation, there are difficulties in finding and taking biopsies of lesions inside the parenchymal and cavernous organs, and the cost is high, and there are certain requirements for patients’ cardiopulmonary function.
2.Gynecological diseases causing ascites
2.1 Ovarian cancer is a common cause among female patients with malignant ascites. A retrospective study found that 37.7% of ovarian cancer patients had combined ascites, and about 1/4 of patients with malignant ascites had ovarian cancer [2]. Combined pelvic masses, rapid growth of ascites, irregular, solid, poorly mobile gynecologic examination masses, and palpable nodules without tenderness in the rectal fossa of the uterus should alert for ovarian tumors.
Vaginal ultrasound and color blood flow ultrasound are effective imaging methods to detect and diagnose ovarian malignant tumors. Morphologic features of the tumor and tumor blood flow are the most important predictive values of malignancy. Usually thick septa (>3 mm), irregular wall thickness, papillae on the wall, masses containing solid components and containing high velocity, low obstruction blood flow in the septa, papillae or solid components have a high likelihood of malignancy [3]. Serum CA125 is the most widely used tumor marker for ovarian cancer. only 50% of stage I patients have elevated CA125 levels, and in premenopausal women, serum CA125 is elevated in endometriosis, benign ovarian tumors, pelvic inflammatory disease, and during menstruation; therefore, the specificity of CA125 measurement is low and sensitivity to early disease is low [4]. Jacobs et al. noted that postmenopausal postmenopausal women had 85% sensitivity and 97% specificity for the diagnosis of malignancy using a combination of CA125 and ultrasound. In approximately 70% of patients with ovarian cancer, cytology of ascites can provide the diagnosis. The characteristic laparoscopic presentation is characterized by white to pink or red nodules that can be seen and vary in size, scattered in the visceral and mural peritoneum. Patients with malignant ascites of other tissue origin usually have a poor prognosis, and patients with ovarian cancer with combined ascites have a relatively high survival rate. Treatment of ascites associated with ovarian cancer is also different from other tumors and should strive for tumor cytoreductive surgery followed by adjuvant chemotherapy. However, for patients with drug-resistant or recurrent ovarian cancer ascites, palliative treatment may be more appropriate to relieve symptoms.
2.2 Peritoneal primary carcinoma of the peritoneum is histologically indistinguishable from primary plasmacytoma of the ovary. The clinical manifestations are similar to ovarian cancer, and ultrasound, CT examination and CA125 are non-specific and cannot be used to differentiate it from ovarian cancer. Laparoscopy generally reveals slightly enlarged or normal size ovaries with tumor implantation on the surface, extensive growth on the surface of pelvic peritoneum and organs, and large omental pie shape. Histopathological examination by biopsy is the only reliable diagnostic method. The treatment principle is also the same as ovarian cancer.
2.3 Meigs syndrome Megis syndrome is defined as a benign ovarian tumor combined with ascites and pleural fluid, which is very rare. The tumor type may be fibrous tumor, blastocystic tumor, or granulosa cell tumor, with ovarian fibrous tumor being the most common. Ovarian fibroids account for less than 5% of all ovarian tumors, and only 1% of cases have the clinical manifestation of Megis syndrome. The difference between Meigs’ syndrome and pseudo-Meigs’ syndrome is largely theoretical, as the two are identical in treatment. because both are identical in terms of treatment. The pathophysiologic cause of ascites production in both remains unclear.
Some authors speculate that ascites is caused by irritation of the peritoneal surface or by direct compression of the surrounding lymph or blood vessels by a solid ovarian tumor; other studies suggest that ascites is formed by fluid secreted by the ovarian tumor or by increased capillary permeability caused by mediators released by the tumor. When the patient has the tumor removed, ascites usually disappears and the prognosis is better. In contrast to the two mentioned above, pseudo-pseudo-Meigs’ syndrome refers to the development of thoracoabdominal fluid as well as enlarged ovaries secondary to systemic lupus erythematosus. In this syndrome, the ovaries are enlarged but without tumors. In contrast, ascites is usually exudative and may be related to the activation of mesothelial cells in patients with SLE [5].
2.4 Ovarian transitional stimulation syndrome ascites is an important clinical manifestation of ovarian transitional stimulation, a medical complication that develops due to stimulation of the ovaries during reproductive techniques. Ovarian transitional stimulation syndrome (OHSS) is characterized by cystic enlargement of the ovaries and leakage of fluid from the vessels into the tissue interstitium, with a variety of clinical manifestations, ranging from mild discomfort such as slight ovarian enlargement and nausea to severe respiratory distress, oliguria, increased cellular pressure, thrombosis, and even abnormal liver and kidney function.
The diagnosis is not difficult to make based on the history, clinical presentation and characteristic ultrasound manifestations related to reproductive technology. Note that abdominal examinations should be avoided as they may lead to rupture of the enlarged ovary. The most effective treatment is prevention. Ultrasound-guided ascitic fluid puncture is useful only to relieve symptoms of abdominal distension, improve dyspnea, oliguria, and reduce red blood cell pressure. At the same time, fluid replacement, especially colloid supplementation, needs attention. Only very few pharmacological interventions improve extravascular leakage; however, diuretics do not work. Currently, a prospective, randomized, double-blind study of oocyte donors with risk factors for developing OHSS found that the use of an effective dopamine agonist significantly reduced ascites production [6].
2.5 Endometriosis Endometriosis is a relatively common gynecologic condition that refers to the presence of endometrium and mesenchyme in areas outside the uterine cavity. Common clinical manifestations include pelvic pain, dysmenorrhea, painful intercourse and infertility. The ability of endometriosis to form ascites is quite rare. The earliest reported case was in 1954, and fewer than 50 cases have been reported since then. The majority of patients are infertile, non-Caucasian, fertile women. The ascites is often massive and can be combined with pleural fluid. Because endometriosis-associated ascites is often combined with pelvic masses, decreased appetite, wasting, and elevated tumor markers, it is often misdiagnosed as ovarian malignant ascites.
Although Zeppa et al. showed that cytology of ascites can successfully detect endometriosis, the definitive diagnosis in most patients is still based on surgical pathology [7]. The pathophysiologic cause of endometriosis ascites remains unclear. A widely accepted hypothesis for the cause of ascites is that endometrial cells dispersed into the peritoneal cavity irritate the peritoneum and produce ascites. However, Donnez et al. reported that ascites can result from the rupture of endometriotic cysts [8], and Jeanes et al. reported a more rare case in which ascites forms due to endometriosis involving the liver [9]. Therefore, the ultimate treatment for this type of ascites is the removal of the ovaries and their function. Both progestin preparations and pharmacological treatment with gonadotropin-releasing hormone (GnRH) are less reliable than surgical debulking and may result in treatment failure or recurrence of ascites.
2.6 Pelvic tuberculosis can cause ascites, and its clinical manifestations are not specific and are similar to those of malignant tumors. The main clinical features are chronic disease, poor nutritional status, and low socioeconomic status with pelvic pain, abdominal distention, weight loss, fever, and infertility. Ultrasound shows ovarian masses that are usually small; the septa within the masses are usually multiple, weak and incomplete; and the lesions are lined with highly obstructed blood flow. This allows for differentiation from ovarian tumors. The results of ascites analysis showed high total leukocyte count (≥500/mm3), predominantly lymphocytes, high protein concentration, and low serum ascites clear protein gradient suggesting tuberculous ascites. An increase in ascites adenosine deaminase activity helps to differentiate bacterial or malignant ascites. Recently, polymerase chain reaction assays for Mycobacterium and adenosine deaminase have been considered a reliable diagnostic technique.
The sensitivity of ascites smears for direct detection of Mycobacterium tuberculosis is only 0-2%, and the positivity rate for culture of Mycobacterium tuberculosis is only 10-50%, and more importantly, microbial culture is time-consuming, making this method impractical. With the remarkable development of laparoscopic technology, laparoscopic surgery has become an effective diagnostic tool, and the diagnosis of 85% to 90% of patients with tuberculous peritonitis can only rely on laparoscopic examination and histopathological diagnosis. The characteristic laparoscopic manifestations are free ascites with multiple milky white nodules 0.5-1 cm in diameter, widely distributed in the peritoneum, intestinal plasma membrane and greater omentum, and extensive “violin string-like” fibrous adhesions between the peritoneum and the intestinal tube, omentum and liver, which makes laparoscopic operation difficult and sometimes requires This makes laparoscopic operation difficult and sometimes requires dissection. In addition, areas of inflammatory hemorrhage in the peritoneum can sometimes be visualized.
Simultaneous peritoneal biopsy and pathologic examination reveals granulomas with Langerhans’ giant cells and central necrotic areas, as well as antacid staining, with a diagnostic sensitivity of nearly 100%. Although pelvic TB is usually secondary to a previous TB infection, only about 1/2 of patients with TB peritonitis have a positive tuberculin skin test, and chest radiography is of limited help in identifying pelvic TB. After diagnosis, the patient is treated with anti-tuberculosis drugs and the ascites usually resolves.
In conclusion, female patients with ascites need to pay special attention to gynecologic diseases that may cause ascites, based on a detailed medical history and physical examination, combined with appropriate ancillary tests for diagnosis and differential diagnosis. Ascites puncture and ascites examination is a specific method, but plays a limited role in determining the cause. In patients with diagnostic difficulties, endoscopy is safe and effective. Treatment of ascites relies on removing the cause of ascites production – the etiology. Most ascites associated with gynecologic disease is able to resolve with prompt diagnosis and appropriate treatment.