Minimally invasive surgery for pleuroperitoneal communication complicating peritoneal dialysis

Pleuroperitoneal communication (PPC) is an uncommon but serious complication of continuous ambulatory peritoneal dialysis (CAPD). At present, there are many kinds of treatment options, with different effects. We describe our single-institutional experiences in the minimally invasive surgery of pleuroperitoneal communication complicating continuous ambulatory peritoneal dialysis in detail. Our study consecutively enrolled 12 pleuroperitoneal communication patients complicating CAPD. All patients underwent direct closure of the defective diaphragm and mechanical rub pleurodesis under video-assisted thoracoscopy. What is more, pseudomonas aeruginosa injection was infused into the thoracic cavity postoperatively to further promote pleural adhesion, which was the innovation of our study. After 1.0–8.3 months of CAPD, all 12 patients presented hydrothorax in the right side. All these patients received surgery 7–179 days (18.0 ± 49.5 days) after onset. Bleb-like lesions situated on the diaphragm were discovered in all patients and three patients also had obvious hole on the surface of diaphragm. Pseudomonas aeruginosa injection was infused into the thoracic cavity postoperatively, and three cases showed fever with remission after 2–3 days of symptomatic treatment. The time from surgery to restarting CAPD ranged from 14 to 47 days, with a median of 20 days. There was no recurrence of hydrothorax and transformation to hemodialysis during the follow-up period (median: 7.5 months). Video-assisted thoracoscopic direct closure of the defective diaphragm and mechanical rub pleurodesis plus chemical pleurodesis using pseudomonas aeruginosa injection postoperatively is a safe and effective option for the treatment of pleuroperitoneal communication complicating continuous ambulatory peritoneal dialysis with 100% success rate.


Introduction
Continuous ambulatory peritoneal dialysis (CAPD) is an effective and widespread replacement therapy for patients with end-stage chronic kidney disease (CKD).Pleuroperitoneal communication (PPC) is a rare but serious complication among patients undergoing continuous ambulatory peritoneal dialysis (CAPD), which results in the occurrence of hydrothorax, with an incidence of about 1.6% [1].Moreover, hydrothorax is the predominant cause of the permanent transition from CAPD to hemodialysis [2].Therefore, it is necessary to perform effective treatment for the PPC.However, there is still no consensus on the choice of the standard method of management.So far, many varying therapeutic methods including nonsurgical approach and surgery have been reported with different degrees of effect [3], but these 1 3 methods are mainly elaborated by few cases of a single institution and have not been well characterized.In our study, we retrospectively analyze twelve surgical cases of PPC complicating CAPD from July 2020 to September 2022, and describe their clinical presentations, surgical procedure, intraoperative findings and postoperative condition in detail.

Patients
From 2020 to 2022, a total of 1156 patients underwent peritoneal dialysis in the First Affiliated Hospital of Zhejiang University School of Medicine, and 15 patients (1.3%) presented pleuroperitoneal communication after peritoneal dialysis.Among them, three cases chose to receive conservative treatment, and finally transferred to hemodialysis due to poor effect, and 12 cases (8 females and 4 males) eventually underwent minimally invasive surgery at the Thoracic Surgery Department.On average, there are four such patients in our center who undergo surgery every year.In our study, we retrospectively analyze these 12 surgical cases of PPC complicating CAPD.
The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).This study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine (2022 IIT No. 1023), and we obtained written consent from patients to access their medical record information.We obtained follow-up data by patient's regular examination or treatment in our hospital.If we cannot complete it, contacting patients by telephone or WeChat would be adopted by us.The follow-up date was not ended until termination of the study.

Surgical procedure
All patients underwent direct closure of the defective diaphragm and mechanical rub pleurodesis under video-assisted thoracoscopy.Under general anesthesia, the patient was intubated with a double-lumen endotracheal tube and put in left-sided lateral decubitus position with unilateral pulmonary ventilation during surgery.The observation port was made for the thoracoscope at the forth costal interspace along the middle axillary line, and the operation hole was created at the fifth costal interspace along the anterior axillary line with an incision measuring 2 cm.The check-air method was adopted intraoperatively to determine the diaphragmatic defect.Normal saline was poured into the pleural cavity to cover the diaphragm and the peritoneal dialysis tube was connected to the CO 2 instrument to establish an artificial pneumoperitoneum maintaining the pressure at 14-20 cmH 2 O. Then operating table was adjusted to keep patient's head high and feet low, and the defective diaphragm was identified by air bubbles leakage and direct inspection under the thoracoscopy.The lesion was closed directly with 4-0 nonabsorbable proline sutures in a continuous pattern, and finally, we rubbed the parietal pleura near the diaphragm until there was obvious bleeding so as to produce pleural adhesion and achieve the purpose of fixing the pleura.After surgery, pseudomonas aeruginosa injection (inactivated pseudomonas aeruginosa) was infused into the thoracic cavity to further promote pleural adhesion.
The main component of pseudomonas aeruginosa injection is inactivated pseudomonas aeruginosa.The specification of each injection is 1.0 ml, containing 1.8 ^ 10 9 bacteria.It was produced by the Beijing Wante'er Biological Pharmaceutical limited company.We added 5 injections into 50 ml of normal saline, then injected them into the thoracic cavity through the drainage tube, and then clamped the drainage tube for 2 h to observe the patient's reaction.Side effects are generally mild, mainly chest pain and fever.In addition, they disappeared after symptomatic treatment.

Results
The baseline clinical characteristics of patients are shown in Table 1.There was no evidence of heart failure, liver cirrhosis, hypoalbuminemia, fluid overload, tuberculous or malignant pleural fluid.Patient's age ranged from 35 to 71 years (44 ± 10.6 years).All patients received a total volume of 6-8 L of 1.5% and/or 2.5% dialysis solutions every day.After 1.0-8.3months (2.9 ± 2.6 months) of CAPD, patients presented reduction of ultrafiltration volume (n = 12), shortness of breath (n = 11) and cough (n = 7).All 12 patients exhibited hydrothorax in the right side (Fig. 1A).All patients were diagnosed by image (ultrasonography and/or CT) and result of chemical component of the pleural effusion obtained by thoracentesis.All patients had a high glucose concentration in the pleural effusion which is similar to the level in the dialysis solution.Moreover, the methylene blue test was performed in case 5, case 9, and case 12, and the result was positive (Fig. 1B).In addition, computerized tomography peritoneography was adopted in case 4, but the result was negative.
Among them, four cases (case 1, case 4, case 7, and case 11) received conservative treatment before operation such as: changing the total volume of dialysis solution and intermittent extraction of pleural effusion before decision to surgery, but the effect was poor.Moreover, one patient (case 8) converted to hemodialysis for 3 months prior to operation, and then underwent surgery with an urgent desire to go on peritoneal dialysis again.
These patients all underwent video-assisted thoracoscopic direct closure of the defective diaphragm (Fig. 2C) and mechanical rub pleurodesis 7-179 days (18.0 ± 49.5 days) after onset (Table 2).The mean operation time was 58.5 ± 29.4 min (range 27-150 min).In one patient (case 2), the operation time was 150 min due to resetting peritoneal dialysis catheter during surgery.Bleblike lesions situated on the diaphragm were discovered in all patients with direct inspection under the thoracoscopy (Fig. 2A).What is more, two patients (case 6, case 11) had two obvious holes on the surface of diaphragm with one patient (case 12) one obvious hole and we could see massive air bubbles leaking from these defects through thoracoscopy (Fig. 2B).The phenomenon of air bubbles leakage the defective diaphragm was inapparent in other cases.
The mean postoperative drainage time was 5.0 ± 1.4 days (range 3-7 days).In addition, before removing the drainage tube, pseudomonas aeruginosa injection was infused into the thoracic cavity to further promote pleural adhesion.After infusion, three cases (case 3, case 6, and case 10) had a fever (38-39 ℃) with remission after 2-3 days of symptomatic treatment.In addition, there was no evident discomfort in the rest patients.There were no complications related to surgery in all eleven patients.
The time from surgery to restarting CAPD ranged from 14 to 47 days, with a median of 20 days (Table 3).Postoperatively, the average follow-up period was 7.5 ± 7.8 months (range 1-25 months).In addition, there was no recurrence of hydrothorax and transformation to hemodialysis.All patients kept well on CAPD currently.

Discussion
Among patients receiving CAPD, the incidence of PPC is 1.6%, and about 50% of these patients are compelled to terminate CAPD and turn into hemodialysis due to secondary hydrothorax [1,2].Hydrothorax occurs prevalently in women and on the right side [3], similar to our study.The nosogenesis of hydrothorax is still not clear.Possible mechanisms include drainage disorder of diaphragmatic lymphatics, thoracic duct, congenital or acquired diaphragmatic defects or blebs, and pleuro-peritoneal pressure gradient [4].Patients commonly present dyspnea and cough, but some of them can be asymptomatic [1].In addition, there is a continuous reduction in ultrafiltration in these patients.In the present study, all 12 patients had reduction of ultrafiltration volume and 11 patients presented Based on the close relationship between pleural effusion, clinical presentations and implementation of CAPD, the diagnosis is usually not difficult.The commonly preoperative diagnostic methods include: biochemical analysis of pleural effusion, the methylene blue dye test, isotopic scanning and contrast computerized tomography (CT) peritoneography [5,6].A high glucose concentration in the pleural effusion, which is similar to the level in the dialysis solution, indicates the diagnosis of PPC complicating CAPD [7].Chow et al. found that there was 100% sensitivity and specificity for differentiating hydrothorax caused by pleuroperitoneal communication from other reasons when the difference between the concentration of glucose in pleural effusion and that in serum exceeded 50 mg/dl [2].In addition, Momenin et al.
showed that there was a low pleural fluid-to-serum glucose gradient in the diagnosis of PPC complicating CAPD [8].In our study, we used a high glucose concentration in the pleural effusion as a diagnostic marker.In addition, all patients existed a high pleural effusion glucose level and the pleural fluid-to-serum glucose concentration difference exceeded 50 mg/dl.Some studies reported that the methylene blue test was negative in the tested patients [4,5] and could cause abdominal pain and even chemical peritonitis [9].In the present study, the methylene blue test was positive among these tested cases and there was no evident discomfort in them.CT peritoneography is not sensitive in detecting PPC and is expensive for patients [10].Tang et al. reported that only one patient was positive in three patients undergoing CT peritoneography [4].In addition, CT peritoneography was negative in the tested subject in our study.The reason may be that the high intrapleural pressure produced by massive pleural effusion impedes tracer migration.There are many varying therapeutic methods such as: conservative approach (temporary discontinuation of CAPD, temporary change to hemodialysis, reduction of the CAPD exchange volume, and repeated thoracocentesis) [2], pleurodesis (mechanical rub pleurodesis [11] and chemical pleurodesis adopting talc [12], tetracycline [13], fibrin glue [14], OK-432 [13], autologous blood [15] etc.), and surgery [4,5,7] according to reports until now.No matter what kind of therapeutic method was adopted, the required pleural adhesion could not always be firmly formed, leading to the recurrence of hydrothorax [3].There is still no consensus on the choice of the standard method of management.In our study, we chose to perform video-assisted thoracoscopic direct closure of the defective diaphragm and mechanical rub pleurodesis, and pseudomonas aeruginosa injection was infused into the thoracic cavity postoperatively to further promote pleural adhesion in all patients.Video-assisted thoracoscopic surgery can well display the entire parietal pleura and diaphragm surface with minimal incisions, and realize diaphragmatic defects diagnosis.Direct visualization, infusion of colored dialysate into the peritoneal and cavity check-air-leakage method under the thoracoscopy can be used to detect diaphragmatic lesions including small defects, bleb-like lesions, and thin walls, making a definite diagnosis of PPC [14,16].Not all cases can find obvious defects, perhaps because these defects are too small to be found [17].In our study, we discovered bleblike lesions in all patients with direct inspection and obvious holes in two patients through check-air-leakage method under the thoracoscopy.Currently, thoracoscopic surgery includes diaphragm repair [18], mechanical rub pleurodesis and chemical pleurodesis [4], with different degrees of effect.Most studies only used one or two of these methods.However, in our study, we chose all of them.Video-assisted thoracoscopic direct closure of the defective diaphragm and mechanical rub pleurodesis was performed in all patients, and pseudomonas aeruginosa injection was infused into the thoracic cavity postoperatively to further promote pleural adhesion.It was these triple means that ensured the success rate and finally achieved 100% success rate.There were no complications related to surgery, and no recurrence of hydrothorax and transformation to hemodialysis during the followup period (median: 7.5 months).Tang et al. evaluated the safety and efficacy of video-assisted thoracoscopic (VATS) talc pleurodesis in the treatment of hydrothorax complicating CAPD, and they found one patient (10%) recurrence and finally seven patients (70%) were well on CAPD [4].Shoji et al. described surgical repair of pleuroperitoneal communication with CAPD, and they found two patients (50%) change to hemodialysis at the final follow-up.Thus, it can be seen that our method is a safe and effective choice [14].Chemical pleurodesis using pseudomonas aeruginosa injection was a novel method, which was first reported in our study.It was the innovation of our study.In patients infusing pseudomonas aeruginosa injection, only three cases showed fever with remission after 2-3 days of symptomatic treatment, and there was no evident discomfort in the rest patients.The reaction to pseudomonas aeruginosa injection was mild and manageable.
In conclusion, direct closure of the defective diaphragm and mechanical rub pleurodesis under the thoracoscopy plus chemical pleurodesis using pseudomonas aeruginosa injection postoperatively is a safe and effective option for the treatment of pleuroperitoneal communication complicating continuous ambulatory peritoneal dialysis with 100% success rate.However, the effectiveness of our findings requires more larger randomized controlled trials to confirm because of the small sample size.

Fig. 1 Fig. 2
Fig. 1 Diagnosis of hydrothorax.A Computed tomography revealed massive pleural effusion in the right side; B the result of methylene blue test was positive 2020C03058), the Zhejiang Province Lung Tumor Diagnosis and Treatment Technology Research Supported by the Center (grant numbers JBZX-202007), the Zhejiang Provincial Traditional Chinese Medicine (Integrated Traditional Chinese and Western Medicine) Key Discipline (grant numbers 2017-XK-A33), and the Zhejiang Provincial Natural Science Foundation (grant numbers LY19H160039).

Table 1
The baseline clinical characteristics of patients with PPC complicating CAPD PPC pleuroperitoneal communication, CAPD continuous ambulatory peritoneal dialysis a Time between initiation of CAPD and onset of hydrothorax b Glucose concentration in the pleural effusion after onset c Computerized tomography peritoneography was negative

Table 2
Surgery-related information of patients with PPC complicating CAPD PPC pleuroperitoneal communication, CAPD continuous ambulatory peritoneal dialysis a The main component of pseudomonas aeruginosa injection is inactivated pseudomonas aeruginosa