Does Hyperthermia Induce Peritoneal Damage in Continuous Hyperthermic Peritoneal Perfusion?

To investigate the mechanisms of the peritoneal damage induced by continuous hyperthermic peritoneal perfusion (CHPP), protein and fluid loss during and after CHPP and continuous normothermic peritoneal perfusion (CNPP) was studied. Sixteen patients with advanced gastric cancer underwent peritoneal perfusion therapy with saline solution containing 150 to 300 mg cisplatin and 30 to 60 mg mitomycin C for 60 minutes. The temperature in Douglas' pouch was maintained at 42.0°C in the CHPP group (n= 9) and 37.0°C in the CNPP group (n= 7) during perfusion. No statistical differences were found in patients' characteristics between the groups except the maximum temperature in Douglas' pouch during perfusion (41.6°± 0.4°C and 37.6°± 0.4°C in CHPP and CNPP groups, respectively, p < 0.05). The amount of protein lost into the perfusate was 0.35 ± 0.22 g/kg body weight in the CHPP group and 0.37 ± 0.19 g/kg in the CNPP group, showing no significant difference. On the day of surgery, there was no significant difference in the amount of protein and fluid lost through the abdominal drains between the CHPP group (27.9 ± 24.6 mg/kg/hr and 0.94 ± 0.63 ml/kg/hr, respectively) and the CNPP group (25.9 ± 8.6 mg/kg/hr and 1.03 ± 0.31 ml/kg/hr, respectively). We could not find any significant differences in postoperative protein and fluid loss between the groups on the following 3 days either. We conclude that the peritoneal damage by CHPP is not caused by the hyperthermia but by the peritoneal perfusion with saline solution containing anticancer drugs.     

Does Peritoneal Dialysis Catheter Insertion by Interventional Nephrologists Enhance Peritoneal Dialysis Penetration?

Traditionally peritoneal dialysis (PD) catheter was implanted by surgeons using mini-laparotomy or open technique in Malaysia. We introduced peritoneoscopic Tenckhoff catheter insertion technique since the beginning of our PD program. Data were collected from the start of our PD program in February 2006 until April 2008. All Tenckhoff catheters were inserted by nephrologists using the peritoneoscope technique. We also compare the penetration rate of PD versus hemodialysis (HD) in our center, as well as comparing to national PD penetration rate. There were 83 patients who underwent 91 peritoneoscope Tenckhoff catheter insertion procedures from March 2006 until April 2008. The patients were mostly female (66%) with the mean age of 51.99 +/- 1.78 years and the majority (67%) of them were diabetics. All together there were 749.7 patient-months at risk and the overall peritonitis rate was 1 in 93.7 patient-months. The 1-year catheter survival was 86.5%. Primary catheter failure (defined as failure of the catheter within 1 month of insertion) occurred in 16 procedures (17.6%). The main cause of catheter malfunction was catheter tip migration and omentum wrap. The penetration ratio of PD when compared with HD in our center is 44.8%, which is about 4.5 times the national average. With our integrated care approach where nephrologist was heavily involved from the outset of renal replacement therapy discussion, PD access implantation to the assistance of spoke person to whom new patient can identify with, we were able to achieve PD penetration rate which far exceeds that of the national average.     

Peritoneal dialysability of “Uraemic substances”

Small- and middle-molecular substances were studied for dialysability in patients on chronic peritoneal dialysis. The peritoneum, as a dialysis membrane, was found to be passed readily by middle-molecular substances held responsible for the toxic symptoms of uraemia. Peritoneal dialysis is regarded on these grounds as an efficient procedure in the management of renal failure.     

When Is Curative Gastrectomy Justified for Gastric Cancer with Positive Peritoneal Lavage Cytology but Negative Macroscopic Peritoneal Implant?

For gastric cancer patients who have no peritoneal seeding at a macroscopic level but positive results in the peritoneal lavage cytology (PLC), the prognostic benefit expected by surgical resection is still controversial. During the period 1975–1994 as series of 417 consecutive patients without distant organ metastases underwent surgical resection for gastric cancer that had invaded the subserosal or deeper layers of the stomach wall. Immediately after laparotomy, the pouch of Douglas was washed with 100 ml of physiologic saline solution, and the fluid was collected for cytologic examination (four slide glasses) using Giemsa and Papanicolaou staining methods. According to the macroscopic (P) and cytologic (Cyt) results, the 417 patients were classified into three groups: P⁺ (n = 97); P⁻/Cyt⁺ (n = 25); and P⁻/Cyt⁻ (n = 295). Their 3-year survival rates after surgical resection were 4%, 24%, and 48%, respectively (p = 0.0001: P⁻/Cyt⁺ vs. P⁻/Cyt⁻; p = 0.0018: P⁻/Cyt⁺ vs. P⁺. Among the 25 P⁻/Cyt⁺ patients, postoperative survival was not associated with the T stage, N stage, cellular atypism, or cluster formation but with the number of cancer cells per slide during PLC. The 3-year survival rate was 35% for the subgroup with fewer than 10 cancer cells per slide (17 patients) and 0% for the other subgroup with 10 or more cancer cells per slide (8 patients) (p = 0.017). For P⁻/Cyt⁺ patients, who represent a subgroup of gastric cancer patients with an intermediate survival rate between the P⁻/Cyt⁻ and P⁺ patients, the number of cancer cells observed during PLC offers a potent prognostic indicator for the gastrectomy.     

TGF-β1 Promotes Lymphangiogenesis during Peritoneal Fibrosis

Peritoneal fibrosis (PF) causes ultrafiltration failure (UFF) and is a complicating factor in long-term peritoneal dialysis. Lymphatic reabsorption also may contribute to UFF, but little is known about lymphangiogenesis in patients with UFF and peritonitis. We studied the role of the lymphangiogenesis mediator vascular endothelial growth factor-C (VEGF-C) in human dialysate effluents, peritoneal tissues, and peritoneal mesothelial cells (HPMCs). Dialysate VEGF-C concentration correlated positively with the dialysate-to-plasma ratio of creatinine (D/P Cr) and the dialysate TGF-β1 concentration. Peritoneal tissue from patients with UFF expressed higher levels of VEGF-C, lymphatic endothelial hyaluronan receptor-1 (LYVE-1), and podoplanin mRNA and contained more lymphatic vessels than tissue from patients without UFF. Furthermore, mesothelial cell and macrophage expression of VEGF-C increased in the peritoneal membranes of patients with UFF and peritonitis. In cultured mesothelial cells, TGF-β1 upregulated the expression of VEGF-C mRNA and protein, and this upregulation was suppressed by a TGF-β type I receptor (TGFβR-I) inhibitor. TGF-β1–induced upregulation of VEGF-C mRNA expression in cultured HPMCs correlated with the D/P Cr of the patient from whom the HPMCs were derived (P<0.001). Moreover, treatment with a TGFβR-I inhibitor suppressed the enhanced lymphangiogenesis and VEGF-C expression associated with fibrosis in a rat model of PF. These results suggest that lymphangiogenesis associates with fibrosis through the TGF-β–VEGF-C pathway.The decrease in ultrafiltration capacity that is associated with the high peritoneal solute transport that is observed after prolonged peritoneal dialysis (PD) treatment is a major reason for its discontinuation.^1–4 Several studies have shown that a higher peritoneal solute transport rate is associated with reduced survival of PD patients.^1,2,5 The characteristic features of chronic peritoneal damage in PD treatment are associated with submesothelial fibrosis and neoangiogenesis.^6,7 Analyses of the surface peritoneum showed no significant changes in vessel density with duration of PD.^6,8 In addition, the vessel density in patients with ultrafiltration failure (UFF) was significantly higher than the vessel density in normal individuals or non-PD patients, but it was not higher than the vessel density in patients undergoing PD.⁶ These findings suggest that factors other than increased vascular density may be involved in disease states associated with increased transport of peritoneal membranes. In addition, the relationship between peritoneal fibrosis and UFF remains obscure.Blood capillaries have a continuous basal lamina with tight interendothelial junctions and are supported by pericytes and smooth muscle cells. In contrast, lymphatic capillaries are thin-walled with a wide lumen and do not contain pericytes or basement membrane. The structures of lymphatic vessels are suitable for the removal of tissue fluid, cells, and macromolecules from the interstitium.^9–11 If lymphangiogenesis develops in the peritoneal membrane, absorption of the PD fluid could be increased and lead to UFF. An increase in the number of lymphatic vessels has recently been reported in several disease conditions, including tumor metastasis,^12–15 chronic respiratory inflammatory diseases,^16–18 wound healing,¹⁹ and renal transplant rejection.^20,21 We recently reported that lymphangiogenesis had developed in tubulointerstitial fibrosis of human renal biopsy specimens,²² and we also reported the mechanisms of lymphangiogenesis in rat unilateral ureteral obstruction models.²³The lymphatic absorption rate, which is measured by the rate at which intraperitoneally administered radioactive serum albumin or macromolecule dextran 70 disappears, is significantly higher in patients with UFF, and lymphatic reabsorption is considered to be one of the causes of UFF.^24–27 However, the results from these clinical approaches have been controversial.^28,29 In addition, little is known about the pathology and the process of lymphangiogenesis in patients with UFF and peritonitis.In this study, we investigated lymphangiogenesis and the expression of vascular endothelial growth factor-C (VEGF-C), which is a potentially important mediator of lymphangiogenesis, in human peritoneal tissues, PD effluent, and peritoneal mesothelial cells. We also explored VEGF-C induction by TGF-β1 in the human mesothelial cell line (Met-5A) and cultured human peritoneal mesothelial cells (HPMCs) from the spent PD effluent of patients with varying rates of peritoneal transport. Finally, we explored the relationship between peritoneal fibrosis and lymphangiogenesis in rats that were administered chlorhexidine gluconate (CG) into the abdominal cavity, which provides a model of chemically induced peritoneal inflammation/fibrosis.^30–32 This work is the first report to show that lymphangiogenesis is linked to the peritoneal fibrosis that is often associated with a high peritoneal transport rate.     

Peritoneal dialysis–associated peritonitis caused by propionibacteria species

There are an increasing number of reports about unusual causes of peritonitis in peritoneal dialysis (PD) patients. The Propionibacteria species is a microorgasnism that is a normal skin flora. Under the presence of certain risk factors, it may produce serious infections. Patients at risk of having Propionibacteria sp infections have malignancy, diabetes mellitus, foreign bodies, or immunodeficiency. We describe a PD-associated peritonitis in a 51-year-old woman that was caused by Propionibacteria sp. This patient's risk factors for developing Propionibacteria sp peritonitis include a history of CREST syndrome, malignancy of the breast, and recent catheter surgery. To our knowledge, this is the first case of a PD-associated peritonitis caused by Propionibacteria sp reported in the literature.     

Peritoneal dialysis catheter placement—is laparoscopy an option?

Abstract Peritoneal dialysis (CAPD) is the preferred and gentlest type of dialysis in patients with end-stage renal disease (ESRD). One of the most frequent complications following peritoneal dialysis catheter (P-catheter) placement is malfunction owing to displacement, which frequently entails major problems for the patient, including reoperation and the risk of having to switch to haemodialysis. Consequently, to ensure optimal P-catheter function and reduce patient morbidity, it is essential to develop and assess new surgical techniques for dialysis catheter placement. The objective of this survey is to describe and assess a laparoscopic-assisted procedure for P-catheter placement. Material and methods Survey of laparoscopic-assisted P-catheter placements performed during a one-year period. The study describes the operative procedure, catheter function and complications. Furthermore, a comparison with open surgery performed in the period is made. Results One of nine P-catheters inserted using laparoscopic-assisted surgery under general anaesthesia was displaced while four of 13 P-catheters inserted using traditional open surgery under local anaesthesia were displaced. The five displaced catheters were subsequently fixed laparoscopically under general anaesthesia. Conclusion Laparoscopic P-catheter placement is uncomplicated, quick and reduces P-catheter displacement frequency. Drawbacks include costly equipment and the need for general anaesthesia. Future follow-up will reveal whether laparoscopically placed P-catheters yield longer-lasting and better-functioning catheters than traditionally placed P-catheters.     

Peritoneal Sclerosis: One or Two Nosological Entities?

The frequency, pathology, animal models, pathogenesis, clinical manifestations, diagnostic criteria, therapy and prevention of peritoneal sclerosis are reviewed. Many of these aspects have a bimodal configuration which suggests that peritoneal sclerosis, usually considered a single pathology in peritoneal dialysis, is actually two distinct nosological entities: simple sclerosis and sclerosing peritonitis. The former is very frequent, with minor anatomical alterations and low clinical impact; it is reproducible in animals by means of peritoneal dialysis, and is clearly due to the poor biocompatibility of peritoneal dialysis solutions. The latter is rare, with radical anatomical alterations and high mortality requiring valid methods of diagnosis, therapy and prevention; it can only be reproduced in animal models by means other than peritoneal dialysis and seems to be due to factors both related and unrelated to peritoneal dialysis.     

Correlation of Radiologic with Surgical Peritoneal Cancer Index Scores in Patients with Pseudomyxoma Peritonei and Peritoneal Carcinomatosis: How Well Can We Predict Resectability?

Introduction

Pseudomyxoma peritonei (PMP) and peritoneal carcinomatosis (PC) arises from primary or secondary peritoneal cancer and can be treated with complete surgical removal of disease. Suitability for surgery is based on a peritoneal cancer index (PCI), with a PCI?≥?20 representing unresectable disease.

Aims

Compare preoperative imaging with surgical findings based on PCI.

Methods

All cases of patients with PMP and PC undergoing cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy (HIPEC) between 2010 and 2014 were included. Two staff radiologists blinded to surgical PCI scores retrospectively reviewed imaging studies to calculate corresponding radiologic PCI scores for each patient. Correlation between radiologic PCI and surgical PCI, as obtained from operative reports, was assessed using Spearman’s rho correlation coefficients. Preoperative assessment of a PCI cutoff of 20 on imaging was compared with actual surgical PCI using sensitivity, specificity, and positive and negative predictive values.

Results

Forty-two patients had a mean surgical PCI?±?SEM score of 15.1?±?1.3 and mean radiologic PCI of 15.5?±?1.5. The most common tumor histologies were appendiceal (60 %) and colon (33 %) adenocarcinoma and were of low tumor grade (67 %). Correlation between individual radiologists and surgical PCI was 0.59 and 0.62, respectively (all p?<?0.001). When mean radiologic PCI was used, this correlation with surgical PCI improved to 0.64 and to 0.65 when good quality studies only were considered (all p?<?0.001). Radiologic PCI score had a sensitivity of 76 %, a specificity of 69 %, positive predictive value of 85 %, and a negative predictive value of 56 % when compared with the surgical PCI. In patients with a radiologic PCI score?≥?20, 6/13 (46 %) still achieved adequate cytoreduction.

Conclusions

Good quality cross-sectional imaging, combined with overreading and formal assessment of all components of the PCI score yields the best correlation with actual surgical findings. Although preoperative assessment of PCI?≥?20 was reasonably accurate, using this cutoff to assess resectability is problematic as almost half of these patients were still able to undergo adequate cytoreduction. Better assessment of resectability is needed preop, either by refinement of the PCI criteria or routine staging laparoscopy.

     

Glucose Degradation Products (GDP’s) and Peritoneal Changes in Patients on Chronic Peritoneal Dialysis: Will New Dialysis Solutions Prevent these Changes?

As peritonitis rates are declining, the rate of technique failure due to ultrafiltration failure and inadequate solute removal is becoming more important. The failure of the peritoneal membrane to provide adequate dialysis increases with longer duration on PD and correlates with the structural changes in the peritoneal membrane. The exact mechanism responsible for these structural changes is unclear. Conventional PD fluids with glucose as the osmotic agent and more importantly the glucose degradation products (GDP) generated during the heat sterilization of these solutions seems to be responsible for inducing many of these changes in the peritoneum. GDP’s in addition to causing structural and functional alterations of the peritoneal cells is also a leading cause of advanced glycation end-products (AGE) production. There is evidence to suggest that the GDP’s and AGE’s are not limited to the peritoneal cavity and the membrane. They have been shown to get deposited in the vascular walls. In addition they also interact with receptors on endothelial cells and smooth muscle. Thus they could contribute to the vascular dysfunction similar to that seen in diabetes. Formation of GDP’s can be reduced and even be avoided with the use of newer “biocompatible” solutions by sterilizing the glucose and the buffer in separate chambers. These newer solutions have been shown to have several local and systemic advantages over the conventional PD solutions. It remains to be seen whether their chronic use from the start of peritoneal dialysis will prevent the development of peritoneal damage thus allowing these patients to remain on this modality for longer periods.     

Peritoneal dialysis-related infections recommendations: 2010 update. What is new?

The International Society of Peritoneal Dialysis (ISPD) 2010 guidelines on PD-related infections reflect the bulk of knowledge acquired over the last 5 years. It includes new information about causative agents of peritonitis, isolation techniques, or therapeutic regimens. Monitoring of infection rates by reporting of peritonitis and exit site infections, isolated microorganism, and presumed etiology is recommended. Furthermore, special focus is given on careful evaluation of each episode of peritonitis in order to determine the route of infection and to reassess patient’s training. In this article, we record the changes in the last ISPD (2010) guidelines compared to the previous ones published in March 2005.     

Continuous Ambulatory Peritoneal Dialysis – Surgical Technique,Early and Late Complications

Summary BACKGROUND: The wide application of peritoneal dialysis that has developed during the past two decades is above all due to the introduction of continuous ambulatory peritoneal dialysis (CAPD). With CAPD, adequate clearance of urine components via the peritoneum as a semipermeable membrane can be achieved with a method that is usually well accepted by patients and which they themselves can manage. METHODS: On the basis of the literature and the authors experience, indications and contraindications for CAPD, pre- and postoperative management, surgical technique for catheter implantation, possible complications and their avoidance and treatment, are presented and discussed. RESULTS: The frequency of occurrence of one or more complications in peritoneal-dialysis patients such as exit-site or tunnel infections, peritonitis, leakage or catheter dislocation is given in the literature as 56–70 %. During the study period of July 1, 2000, to June 30, 2003, there were 50 patients in the peritoneal dialysis program (48 CAPD, 2 automated peritoneal dialysis, APD) of the Division of Nephrology at the University Hospital in Graz. Of them, 58 % (29 patients) were new to the program (all catheters implanted at the Division of General Surgery, University Surgical Clinic Graz). In the study period, there were 26 cases of peritonitis with a peritonitis rate of 33.5 months, and in two cases, the catheter had to be removed. All exit site infections could be controlled with antibiotics. A tunnel infection was diagnosed in 3 patients and in one case the catheter had to be replaced. One patient experienced postoperative leakage. In 4 cases, postoperative tunnel canal bleeding stopped spontaneously. Transfer to the hemodialysis program was due in two cases to peritonitis that could not be managed conservatively, in two cases to loss of ultrafiltration, in one case to massive abdominal adhesions and in two cases to lack of compliance. CONCLUSIONS: Today, CAPD is a common and patient-friendly alternative to hemodialysis. The outcome of catheter implantation depends mainly on the experience and care of the surgeon, as well as perioperative management. Further factors in the total catheter survival time are the quality of postoperative catheter care and fast response when infections occur. The prerequisite for trouble-free CAPD and efficient management of complications is close cooperation between surgeon and nephrologist with active inclusion of the patient in the decision-making process.     

Continuous Flow Peritoneal Dialysis: Is There a Need for it?

Automated peritoneal dialysis (APD) is the fastest growing technique of peritoneal dialysis. However, recently APD has displayed some limitations imposed by the characteristics of the technique and by the characteristics of the peritoneal membrane of some patients. In general, the advent of a new technique such as continuous flow peritoneal dialysis (CFPD) should be seen as a benefit for several patients based on different considerations: CFPD is a high-efficiency technique which could overcome some of the limitations imposed by other techniques in terms of adequacy targets and performance. CFPD may become a useful tool to keep patients on PD who would otherwise be transferred to hemodialysis. CFPD may present advantages in terms of biocompatibility and also in terms of the possible modulation of the peritoneal solution to patient needs. Recent developments in technology seem to have made CFPD easily feasible and well tolerated. A new era of PD is probably beginning and CFPD will definitely represent one of the key issues in the future of PD.