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ENCAPSULATING PERITONEAL SCLEROSIS: PREVENTION AND TREATMENT

Tsuchiya General Hospital, Hiroshima, Japan

Correspondence to: H. Kawanishi, Tsuchiya General Hospital, 3-30 Nakajima-cho, Naka-ku, Hiroshima 730-8655 Japan. h-kawanishi{at}tuschiya-hp.jp

	ABSTRACT

TOP ABSTRACT PATHOPHYSIOLOGY AND DIAGNOSIS OF... PATHOGENESIS OF EPS IN... EPIDEMIOLOGY OF EPS IN... PREVENTION OF EPS TREATMENT RECURRENT EPS AFTER SURGERY CONCLUSIONS REFERENCES

 

Since the first peritoneal dialysis (PD) patients with encapsulating peritoneal sclerosis (EPS) were reported in 1980, EPS has been considered primarily a fatal complication. The incidence of EPS in PD patients has been reported to be 2.5%, with a negative effect of increasing PD duration (which also augments mortality). Because EPS occurs after withdrawal from PD in more than half of all cases, strict monitoring is necessary when a long-term PD patient is withdrawn from PD. Maintaining patients on standard PD with conventional solutions for more than 8 years is associated with a substantial risk of EPS development. Treatment appropriate to the disease stage is most important in EPS. Basic therapeutic strategies for EPS include the appropriate use of steroids. If bowel obstruction persists, laparotomy and enterolysis should be performed to achieve a complete cure. It is now recognized that EPS need not be a fatal complication of PD.

KEY WORDS: Encapsulating peritoneal sclerosis; EPS; peritoneal deterioration; surgical options.

Encapsulating peritoneal sclerosis (EPS) is regarded primarily as a fatal complication of peritoneal dialysis (PD). To date, diagnosis of EPS has been based on the criteria recommended by an ad hoc committee of the International Society for Peritoneal Dialysis (1), and Peritoneal Dialysis International, Supplement 4, in 2005 (2), in which the key elements are these:

• Presence of clinical symptoms of obstructive ileus, with or without various degrees of systemic inflammatory reaction, such as elevation of serum C-reactive protein (CRP)
  
• Presence of peritoneal thickening and encapsulation, intestinal obstruction, cocooning, and calcification, confirmed by radiologic investigation
  

The condition is defined as "a syndrome continuously, intermittently, or repeatedly presenting with symptoms of intestinal obstruction due to adhesions of a diffusely thickened peritoneum, and a purely clinical diagnosis." "Clinical diagnosis" in this definition has made definitive diagnosis difficult and has contributed to an overdiagnosis of EPS.

The current understanding of EPS can be summarized as follows:

• The condition frequently occurs in patients on long-term PD and is related to peritoneal deterioration.
  
• In some cases, peritonitis is involved in the development of EPS.
  
• Many cases of EPS occur after withdrawal of PD.
  

	PATHOPHYSIOLOGY AND DIAGNOSIS OF EPS

TOP ABSTRACT PATHOPHYSIOLOGY AND DIAGNOSIS OF... PATHOGENESIS OF EPS IN... EPIDEMIOLOGY OF EPS IN... PREVENTION OF EPS TREATMENT RECURRENT EPS AFTER SURGERY CONCLUSIONS REFERENCES

 
In EPS obstructive bowel symptoms develop because of encapsulation of the adhered intestinal tract and formation of a cocoon. The capsule continues from the visceral to the parietal side of the peritoneum, and a cyst retaining ascites seems to be present between the intestinal tract and abdominal wall on abdominal CT. The capsule is constituted mainly of fibrin that oozes from capillary blood vessels outgrowing in the deteriorated peritoneum, and it firmly covers the deteriorated surface (3).

Symptoms do not develop in the early stages because the capsule is thin; but, with thickening and shortening of the capsule over time, tightening the intestinal tract, obstructive bowel symptoms appear. Obstructive bowel symptoms progress slowly in many cases because the whole small intestine is tightened gradually. Thus, movement of the entire small intestine is delayed, but contrast imaging of the small intestine reveals no obviously narrowed region.

Clinical diagnosis of EPS is not difficult in most cases. When PD patients with peritoneal deterioration complain of gastrointestinal symptoms, EPS should be suspected. However, EPS develops in a stepwise manner. We reported a staged classification for EPS based on our experience (4). Understanding the inflammatory stage in that classification is most important in the diagnosis and treatment of EPS.

When EPS is suspected, levels of inflammatory markers should be measured (although elevation of serum CRP is not specific to EPS). When the PD catheter is left in place or ascites can be collected, hemorrhagic effluent or elevated levels of inflammatory mediators and markers of the coagulation–fibrinolysis system such as IL-6 and fibrin/fibrinogen degradation products, or both, are indicative of EPS. In addition, detection of edematous changes in the intestinal wall by imaging [abdominal computed tomography (CT)] is of value for diagnosing the inflammatory stage of EPS. In patients with advanced EPS (encapsulating or ileus stages), EPS is easily diagnosed by abdominal CT.

These procedures are used solely in the clinical setting; a definitive diagnosis of EPS can be established only by macroscopic confirmation of the encapsulated intestine. Laparoscopy at the time of catheter removal has been reported to be useful for this purpose (5).

	PATHOGENESIS OF EPS IN PD

TOP ABSTRACT PATHOPHYSIOLOGY AND DIAGNOSIS OF... PATHOGENESIS OF EPS IN... EPIDEMIOLOGY OF EPS IN... PREVENTION OF EPS TREATMENT RECURRENT EPS AFTER SURGERY CONCLUSIONS REFERENCES

 
To diagnose EPS, a thorough understanding of the development mechanism is necessary. Two factors have been considered with regard to the cause of EPS (4): deterioration of the peritoneum and intraperitoneal inflammation (the "two-hit" theory).

Peritoneal deterioration occurs as a result of long-term exposure to dialysis solution or repeated episodes of peritonitis, and it is characterized pathologically as peritoneal hypertrophy, degenerative sclerosis of the capillary vessels, and proliferative neoangiogenesis. The symptoms of EPS are initiated by adhesion of the deteriorated intestinal tracts, followed by encapsulation of the adhered lesion. Fibrin is considered to be the major component of the capsule, the deposition of which may lead to the development of EPS (3). Even in early-stage PD, when peritoneal deterioration has not yet developed to a significant degree, peritoneal degeneration may readily develop in EPS when complicated by intense bacterial peritonitis. Conversely, in cases of long-term PD and a deteriorated peritoneum, EPS may develop even with mild bacterial peritonitis. In such a case, EPS may even occur via fibrin deposition without peritonitis.

	EPIDEMIOLOGY OF EPS IN PD PATIENTS

TOP ABSTRACT PATHOPHYSIOLOGY AND DIAGNOSIS OF... PATHOGENESIS OF EPS IN... EPIDEMIOLOGY OF EPS IN... PREVENTION OF EPS TREATMENT RECURRENT EPS AFTER SURGERY CONCLUSIONS REFERENCES

 
The incidence of EPS reported from several studies in Japan ranges between 0.8% and 2.8% (6). Reported incidences in other countries vary widely. Rigby et al. reported EPS in 54 of 7374 patients (0.7%) in Australia (7).

Given that that all previous surveys have been retrospective in nature, Kawanishi et al. started a survey in 1999 aimed at prospectively investigating the incidence of EPS and its relationship to withdrawal from PD (8). A total of 1958 patients treated with PD in a total of 57 facilities were observed during a 4-year period. Of these 1958 patients, 48 developed EPS, corresponding to an incidence of 2.5% (3.18 / 1000 patient–years). In 33 of the 48 cases (68.8%), EPS developed after withdrawal from PD. The mean duration on PD was 114.3 months (range: 36 – 201.4 months). The incidence increased and the prognosis worsened with PD duration. The EPS incidences (and mortality rates) were 0%, 0.7% (0%), 2.1% (8.3%), 5.9% (28.6%), 5.8% (61.5%), and 17.2% (100%) in patients that had undergone PD for 3, 5, 8, 10, 15, and more than 15 years respectively. The risk of EPS was high in patients on PD for 8 years or longer (Figure 1). Conversely, a PD duration of less than 8 years using the current glucose-based dialysis solutions was found to be safe.

View larger version (12K): [in this window] [in a new window]   Figure 1 — Probability of remaining free of encapsulating peritoneal sclerosis (EPS) in 1995 prevalent patients (2,8).

	PREVENTION OF EPS

TOP ABSTRACT PATHOPHYSIOLOGY AND DIAGNOSIS OF... PATHOGENESIS OF EPS IN... EPIDEMIOLOGY OF EPS IN... PREVENTION OF EPS TREATMENT RECURRENT EPS AFTER SURGERY CONCLUSIONS REFERENCES

Recently, a new neutral-pH dialysis solution in a two-compartment bag has become available. This solution contains smaller amounts of cytotoxic glucose degradation products, and it shows promise in preventing peritoneal deterioration (9). However, even if the new solution works well in theory, the fact that the use of new solution is likely to allow for an extended duration on PD needs to be considered, as discussed earlier, a likely risk factor for EPS.

To remove fibrin, peritoneal lavage has been performed using a catheter left in place after withdrawal of PD (5,10). However, a prospective multicenter study failed to demonstrate the effectiveness of peritoneal lavage (8). Peritoneal lavage could not improve deterioration of the peritoneum; it only prolonged the time to thickening of the capsules, leading to the development of EPS. Peritonitis as a complication during peritoneal lavage has a reverse effect, inevitably leading to EPS.

	TREATMENT

TOP ABSTRACT PATHOPHYSIOLOGY AND DIAGNOSIS OF... PATHOGENESIS OF EPS IN... EPIDEMIOLOGY OF EPS IN... PREVENTION OF EPS TREATMENT RECURRENT EPS AFTER SURGERY CONCLUSIONS REFERENCES

 
Treatment of EPS includes total parenteral nutrition (TPN), steroid therapy, and surgery.

TPN: The use of TPN alone cannot be expected to improve EPS, and long-term TPN causes bacterial translocation and TPN catheter–related infection, leading to sepsis and death.

Steroid Therapy: In a prospective study (8), 81% of patients were given steroids, but improvements were observed in only 15 patients (38.5%), which questions the effectiveness of steroid therapy. However, dramatic improvement was observed in a case with a longer PD duration, in which steroid therapy was initiated immediately after EPS onset, suggesting the importance of the timing of steroid therapy. Recently, corticosteroid administration was reported to be an effective treatment for EPS in patients with inflammation (4,5,11). Some reports have indicated that methylprednisolone pulse therapy should be recommended during the early stage. Other reports describe the protective effect of low-dose prednisolone on disease progression in the early stage. Steroids, which prevent ascites and fibrin deposition, must be administered immediately after the onset of EPS to be effective (4). A delay in administration results in failure to prevent capsule formation, leading to symptoms of intestinal obstruction.

Surgical Treatment: Based on the recognition that EPS is an ileus and is basically treated by enterolysis of intestinal adhesions, we performed, during 1993 – 2005, complete enterolysis of intestinal adhesions without enterectomy in 86 patients (2,12), all of whom (excluding 5 who died of intestinal perforation) achieved improvement (improvement rate: 94.2%).

Because the basic surgical technique for EPS consists of the sharp ablation of capsules and intestinal adhesions, the surgery itself is not complicated. However, the severity of intestinal degeneration varies with the patient, and determining the area of ablation is important. Usually, the entire intestine is covered with capsules, and fibrous adhesion of the respective intestines is also observed. Therefore, the basic surgical techniques of excision and ablation (or decortication) of capsules are used to make the encapsulated intestine a single tube.

	RECURRENT EPS AFTER SURGERY

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Surgery can reverse the state of intestinal obstruction, but it does not improve the peritoneal deterioration, leading to the re-formation of the capsules and recurrence of EPS in some patients 6 – 12 months later. In 47 patients whom we followed for 2 years, 11 (23.4%) experienced recurrence, and 10 of those patients underwent a second surgery. We observed no differences between the recurrent and nonrecurrent patients in terms of follow-up period, age, history of PD, use or nonuse of steroids after surgery, thickness of the submesothelial compact zone, or inflammatory cell infiltration. However, the number of microvessels (Figure 2) was significantly higher in the recurrent patients (12).

View larger version (9K): [in this window] [in a new window]   Figure 2 — Comparison of relative microvessel numbers between recurrent cases (n = 11) and nonrecurrent cases (n = 36) of encapsulating peritoneal sclerosis (12).

	CONCLUSIONS

TOP ABSTRACT PATHOPHYSIOLOGY AND DIAGNOSIS OF... PATHOGENESIS OF EPS IN... EPIDEMIOLOGY OF EPS IN... PREVENTION OF EPS TREATMENT RECURRENT EPS AFTER SURGERY CONCLUSIONS REFERENCES

 
The development of highly biocompatible peritoneal solutions is essential for the prevention of EPS. In addition, adequate examination of PD patients is important, as is the avoidance of peritoneal deterioration by prescribing optimal PD and preventing peritonitis. If EPS develops, immediate administration of steroids is effective. However, the only established basic treatment of EPS is enterolysis of peritoneal adhesions, and time should not be unnecessarily wasted on conservative treatment. Encapsulating peritoneal sclerosis is not a fatal complication, but a pathologic state that can be completely overcome.

	REFERENCES

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1. Kawaguchi Y, Kawanishi H, Mujais S, Topley N, Oreopoulos DG. Encapsulating peritoneal sclerosis: definition, etiology, diagnosis, and treatment. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis. Perit Dial Int 2000; 20(Suppl 4):S43 -55.[Abstract/Free Full Text]
2. Kawaguchi Y, Saito A, Kawanishi H, Nakayama M, Miyazaki M, Nakamoto H, et al. Recommendations on the management of encapsulating peritoneal sclerosis in Japan, 2005: diagnosis, predictive markers, treatment, and preventive measures. Perit Dial Int2005; 25(Suppl 4):S83 -95.[Abstract/Free Full Text]
3. Dobbie JW. Pathogenesis of peritoneal fibrosing syndromes (sclerosing peritonitis) in peritoneal dialysis. Perit Dial Int 1992; 12:14 -27.[Abstract/Free Full Text]
4. Kawanishi H, Harada Y, Noriyuki T, Kawai T, Takahashi S, Moriishi M, et al. Treatment options for encapsulating peritoneal sclerosis based on progressive stage. Adv Perit Dial2001; 17:200 -4.[Medline]
5. Nakayama M, Yamamoto H, Ikeda M, Hasegawa T, Kato N, Takahashi H, et al. Risk factors and preventive measures for encapsulating peritoneal sclerosis—Jikei experience 2002. Adv Perit Dial 2002; 18:144 -8.[Medline]
6. Nomoto Y, Kawaguchi Y, Kubo H, Hirano H, Sakai S, Kurokawa K. Sclerosing encapsulating peritonitis in patients undergoing continuous peritoneal dialysis. A report of the Japanese Sclerosing Encapsulating Peritonitis Study Group. Am J Kidney Dis1996; 28:420 -7.[Medline]
7. Rigby RJ, Hawley CM. Sclerosing peritonitis: the experience in Australia. Nephrol Dial Transplant 1998;13 : 154-9.[Abstract/Free Full Text]
8. Kawanishi H, Kawaguchi Y, Fukui H, Hara S, Imada A, Kubo H, et al. Encapsulating peritoneal sclerosis in Japan; prospective multicenter survey, Am J Kidney Dis 2004;44 : 729-37.[Medline]
9. Williams JD, Topley N, Craig KJ, Mackenzie RK, Pischetsrieder M, Lage C, et al. The Euro-Balance Trial: the effect of a new biocompatible peritoneal dialysis fluid (Balance) on the peritoneal membrane. Kidney Int 2004;66 : 408-18.[Medline]
10. Moriishi M, Kawanishi H, Kawai T, Takahashi S, Hirai T, Shishida M, et al. Preservation of peritoneal catheter for prevention of encapsulating peritoneal sclerosis. Adv Perit Dial2002; 18:149 -53.[Medline]
11. Junor BJ, McMillan MA. Immunosuppression in sclerosing peritonitis. Adv Perit Dial 1993;9 : 187-9.[Medline]
12. Kawanishi H, Moriishi M, Tsuchiya S. Experience of 100 surgical cases of encapsulating peritoneal sclerosis: investigation of recurrent cases after surgery. Adv Perit Dial 2006;22 : 60-4.[Medline]
13. Numata M, Nakayama M, Nimura S, Kawakami M, Lindholm B, Kawaguchi Y. Association between an increased surface area of peritoneal microvessels and a high peritoneal solute transport rate. Perit Dial Int 2003; 23:116 -22.[Abstract/Free Full Text]

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