Abstract
Objective:
The purpose of this study was to evaluate the feasibility and safety of transgastric natural orifice transluminal endoscopic surgery (TG-NOTES) combined with biopsy in the diagnosis of unknown ascites.
Method:
This retrospective study used data from the first affiliated hospital of Nanchang university on 51 patients who were diagnosed with ascites of unknown origin between January 2013 and May 2019 and experienced peritoneal biopsy through TG-NOTES. The outcome measures included diagnostic accuracy and procedure-related adverse events.
Results:
TG-NOTES was performed successfully in 46 of 51 patients, tuberculous ascites in 38 cases, carcinomatous ascites in 4 cases, cirrhotic ascites in 1 case, and 3 cases showed no obvious abnormalities in pathological result. Five cases failed to be diagnosed because of abdominal adhesions. The diagnostic rate of TG-NOTES was 84.3%. There were no severe procedure-related adverse events and no mortality. All patients had good wound healing and no complaint of discomfort on follow-up.
Conclusion:
The majority of ascites of unknown origin can be expounded through TG-NOTES combined with biopsy without severe complication, therefore, it is a feasible and safe method to detect the cause of unexplained ascites.
Introduction
Ascites is a common sign in clinical practice with varieties of etiologies, including hepatocirrhosis, malignant tumor with peritoneal metastasis, ovarian tumor, and tuberculous peritonitis (TBP). TBP is a familiar cause of ascites, particularly in developing countries. 1 Although the classical symptom of fever, ascites, and abdominal pain is present in most of the patients, diagnosis is more difficult in patients who have vague symptoms or laboratory and radiological finding.2,3 With the advancement of imaging technology and laboratory examinations, the cause of most of ascites can be identified, however, not all ascites can be diagnosed accurately, as a result, treatment may be delayed.
Natural orifice transluminal endoscopic surgery (NOTES) is a significant innovative surgical method in clinical research since the emergence of laparoscopy. In 2004, Kalloo et al performed the first transgastric peritoneoscopy in a porcine model to obtain liver biopsy specimen. 4 Then, Rao and Reddy completed the first human transgastric NOTES (TG-NOTES) appendicectomy. 5 Soon, the first transgastric cholecystectomy in a human was performed by Jacques Marescaux. 6 Since then, NOTESs were applied all over the word.
Natural orifices provide an entry into the body cavity through different lumens for different procedures, such as TG-NOTES cholecystectomy7–9 or appendicectomy,10,11 transvaginal NOTES cholecystectomy12,13 or appendicectomy,14,15 transanal NOTES total mesorectal excision,16–18 and transvesical. 19 Although NOTES has been applied in many studies, it was still controversial in clinical application. Therefore, the purpose of this study was to evaluate the feasibility and safety of TG-NOTES combined with biopsy in the diagnosis of ascites of unknown etiology.
Methods
Patients
Medical records of 51 patients from the first affiliated hospital of Nanchang University between January 2013 and May 2019 were analyzed retrospectively. Patients who meet the following criteria are considered to have unexplained ascites: (1) the patients with ascites were confirmed by physical examination and/or ultrasonography; (2) blood tests including the routine hematology test, biochemistry, tumor markers, and inflammatory markers failed to show a clear diagnosis; (3) no clear diagnosis from routine biochemistry and chromosome examination of ascitic fluid; and (4) imageological examination and routine endoscopic procedures (esophagogastroduodenoscopy and colonoscopy) did not provide a definitive diagnosis.
The patients who had complications of coagulopathy, serious cardiopulmonary insufficiency, peptic ulcer, or gastroduodenal obstruction were eliminated. The procedures and study received approval from the ethical board of the First Affiliated Hospital of Nanchang University and were conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients before the procedure.
Diagnostic work-up for ascites
The routine hematological examination presented 21 patients with anemia (reference range, <120 g/L for men and <110 g/L for women), 3 patients had leukocytosis (>10.0 × 109/L), and 15 patients had leukopenia (<4.0 × 109/L). In biochemical examination, most patients had normal liver and kidney functions, and only 7 patients had mild elevation in serum alanine aminotransferase activity (>40 U/L). The erythrocyte sedimentation rate increased in 29 patients (0–15 mm/h for men and 0–20 mm/h for women).
Tumor marker tests showed that the levels of cancer antigen 125 were significantly elevated in 43 patients (range, 47–1364 U/mL; normal range, <35 U/mL), the level of cancer antigen 19-9 increased to 128.4 U/mL in 1 patient, the level of alpha-fetoprotein (0–7 ng/mL) increased in 1 patient to 25.86 ng/mL, and the level of cancer antigen 153 (<25 U/mL) was elevated in 2 patients to 33.67 and 41.77 U/mL, respectively, but the level of carcinoembryonic antigen (0–10 ng/mL) remained within the normal range.
The skin purified protein derivative test was conducted on 14 patients, 10 of them had positive reactions and 4 had negative reactions. The ELISPOT (TSPOT.TB) was tested in 45 patients, and 31 patients had positive results. The serum TB antibody was performed on 40 patients, only 3 patients had positive results.
Abdominal computed tomography revealed moderate to massive ascites in all patients, cirrhosis in 7 patients, splenomegaly in 6 patients, mesenteric thickening in 12 patients, and mesenteric lymph nodes enlargement in 8 patients. Chest radiographs and computed tomography scans indicated pulmonary tuberculosis lesions in 3 patients, pleural effusion in 35 patients, and pulmonary infection in 22 patients. Esophageal gastroduodenoscopy and colonoscopy were performed to exclude gastrointestinal diseases, but there were no significant findings in all patients.
All patients underwent routine biochemistry and chromosome examination of ascitic fluid. Analysis of the peritoneal fluid revealed predominantly lymphocytic ascites in 40 patients and predominantly neutrophilic ascites in 11 patients, with total nucleated cell counts ranging from 110 to 2500/mL. Ascites lactate dehydrogenase levels ranged from 30 to 1565 U/L (median, 242 U/L). Ascites adenosine deaminase levels ranged from 17 to 52 U/L (median, 28 U/L). The serum ascites albumin gradient was determined to be <11 g/L in 48 patients.
Operative procedure
After general anesthesia and endotracheal intubation, a flexible single-channel video endoscope (model GIF-260; Olympus, Tokyo, Japan) was inserted into gastral cavity; gastric content was aspirated and gastral cavity was cleaned with sterile water completely.
After disinfection with povidone-iodine solution, a 1.0-cm incision was made in the middle of the anterior wall of the gastric body, a high-frequency needle-knife (model HPC-3; Cook Endoscopy, Bloomington, IN, USA) was used to separate the whole layer of the stomach, a guidewire (0.89 mm ·450 cm; Boston Scientific, Natick, MA, USA) was inserted into the incision, and a 1.0 cm × 3.0 cm size endoscopic balloon (model QBD-10X3; Cook Endoscopy) was used to dilate the incision and create a 12–15-mm gastrotomy opening for endoscope access to the enterocoelia, a video endoscope was inserted into the enterocoelia through the transgastric incision, and an artificial pneumoperitoneum was created, then the endoscopist checked each quadrant of abdominal cavity.
TG-NOTES was used to investigate the presence of the peritoneum and omentum, abdominal adhesions, and nodules in the abdominal and pelvic cavities. Appropriate biopsy was performed on suspicious lesions for sampling using gastroscopic biopsy. Endoscopic biopsy specimens were obtained for pathological examination. The transgastric incision was closed by endoclips. Average operating time was 47 minutes.
Results
The mean age of patients was 45.5 ± 17.3 years, men 26, and women 25. The common complaint of patients was abdominal distension. Four patients had previous abdominal surgery, and abdominal adhesions exist in 17 patients observed with endoscope. TG-NOTES was performed successfully in 46 of 51 (90.2%) patients, 5 cases failed to be diagnosed because of abdominal adhesions. In 40 cases, the abdominal wall and omentum were covered by a large number of diffuse randomly distributed white miliary modules.
Among the other 6 patients, 1 patient had a reduced liver size with nodularity, 1 patient had splenomegaly, and 4 patients had a smooth peritoneum with no obvious lesions. We performed biopsies of the mentioned suspected sites, and the pathological results showed tuberculous ascites in 38 cases, carcinomatous ascites in 4 cases (peritoneal metastatic carcinoma, neuroendocrine carcinoma, and peritoneal mesothelial carcinoma, 2, 1, and 1 case, respectively), cirrhotic ascites in 1 case, and 3 cases showed no obvious abnormalities in pathological result. The diagnostic rate of TG-NOTES was 84.3%. There were no severe procedure-related adverse events, and no mortality (Table 1).
Characteristic of Transgastric Natural Orifice Transluminal Endoscopic Surgery
SD, standard deviation; TG-NOTES, transgastric natural orifice transluminal endoscopic surgery.
Therapeutic result
All patients who were diagnosed with TBP were treated with antituberculosis therapy, 1 patient has experienced drug-induced liver injury in hospitalization, and recovered after changing treatment regimen. All patients confirmed with carcinomatous ascites had tumor resection and/or postoperative routine radiochemotherapy or given up treatment. Prophylactic antibiotics with second-generation cephalosporins were commonly prescribed in all patients and a liquid diet was given 3–5 days after the operation. The mean hospital expenses were $2787 (617–10,338).
Follow-up result
After operation, patients will be notified to re-examine gastroscopy at 1 month after surgery. All patients had good wound healing and no complaint of discomfort.
Discussion
Using different approaches of NOTES to diagnose unexplained ascites has been reported in many literature studies and its safety and feasibility have been verified.20–23 It was also controversial in what kinds of NOTESs should be used to diagnose unexplained ascites. Therefore, we investigated the cause of unknow ascites by performing TG-NOTES.
It was obviously different from Europe–American developed countries, where chronic hepatic diseases and abdominal malignancy were common causes of ascites; tuberculosis caused the majority of ascites in developing countries such as China. This is in accordance with our findings. Although TBP is common, sometimes the symptom of it is not typical, even asymptomatic, and differentiate hardly with carcinomatous ascites. Thus, the gold standard is to obtain pathological diagnosis.
Bai et al put forward that the diagnosis rate of ascites can reach up to 92.3% by performing TG-NOTES in 78 patients. 20 The diagnostic rates were 84.3% in our study, none of patients had serious operation-related adverse events that clarified the feasibility and safety of TG-NOTES.
It was accepted that laparoscopic diagnosis of unexplained ascites was a rapid and accurate method.24,25 A systematic review reported that the sensitivity and specificity of laparoscopic biopsy were 93% and 98%, respectively. 26 Diagnostic rate of 98.5% was reported by Yoon et al in cases of ascites of unknown origin. 27 Another advantage was that the tumor detected under laparoscopy can be removed immediately. Nevertheless, intra-abdominal infection, the development of CO2 gas emboli, and injuries to vascular structures by instruments were still reported. 28 In addition, diagnostic laparoscopy is hazardous and less helpful in cases with massive adhesions form of TBP, and requires transfer to laparotomy.23,25,29
The advantages of NOTES, such as improved cosmesis; reduced systemic inflammatory response; elimination of incision infection; and a reduction in pain and convalescence time, hernia formation, and adhesions, have intrigued the interest of many scholars.20,21,30 Notwithstanding that the most concern is that gastrointestinal bacterial translocation induces intra-abdominal infection, many studies confirmed that transgastric manipulation did not lead to peritonitis or abscess.31,32 An randomized controlled trial conducted by Azadani et al illuminated that clinically relevant infections are rare after TG-NOTES procedures compared with laparotomy and laparoscopy. 33
It also reckoned that systemic inflammatory response resulting from TG-NOTES is similar in intensity to laparoscopy.34,35 Prophylactic antibiotics with second-generation cephalosporins were commonly prescribed to all patients, and no cases of infection was seen in our study.
What is more crucial is the safe closure and reliable healing of wound after TG-NOTES. Related research had shown that incisions can heal effectively.20,23,36 In this study, the gastrostomy was closed by endoclips and the incisions were closed successfully. The stomach incision of all patients healed well at subsequent follow-up gastroscopy.
In conclusion, TG-NOTES combined with biopsy can expound the etiology of ascites of unknown origin in majority of cases. Therefore, it is a feasible and effective method for diagnosing ascites of unknown origin.
Footnotes
Authors' Contributions
Concept, critical reviews, and design were contributed by Guo-Hua Li; data collection was done by Pei-Wei Xie; data processing was carried out by Yin-Shui Miao; writing of the article was by Bo-Wen Cheng.
Ethical Approval
The protocol for the research project has been approved by a suitably constituted ethics committee of our hospital.
Disclosure Statement
No competing financial interests exist.
Funding Information
No funding was received for this article.