Dextrose Peritoneal Dialysis Solution Research Articles

Compatibility and stability of non-ionic iodinated contrast media in peritoneal dialysis solution and safe practice considerations for CT peritoneography.

Computerised tomographic (CT) peritoneography is performed on peritoneal dialysis (PD) patients to identify peritoneal boundary defects, dialysate maldistributions and loculated fluid collections. Iodinated contrast media are added to dialysate and infused through the dialysis catheter, and CT images are obtained. Chemical compatibility of contrast media with dialysis solutions has not been studied. In some institutions, pharmacists charged with oversight of compounded sterile preparations have placed a moratorium on the use of contrast media-dialysate mixtures until compatibility data become available. This study was undertaken to examine the compatibility of non-ionic iodinated contrast agents added to PD solution for the performance of CT peritoneography. 100 mL of three non-ionic iodinated contrast agents, iopamidol 370 mgI/mL, iohexol 300 mgI/mL and iodixanol 320 mgI/mL, were mixed with 2 L 1.5% dextrose PD solution and stored at 2-8°C, 25°C and 40°C. Observations at predefined intervals were made over 5 days for visual appearance, turbidity, pH, drug concentration and chemical degradation. Iopamidol, iohexol and iodixanol were stable for 5 days under study conditions. The contrast-dialysate mixture remained clear and colourless, no turbidity changes observed, pH and drug concentrations were stable and no increase in existing impurities or new impurities were detected. The addition of commonly used non-ionic iodinated contrast agents to 1.5% dextrose dialysis solution is chemically stable, meeting the criteria set forth in the standards and guidelines of the US Pharmacopeia and the Institute of Safe Medication Practices. A protocol for performing CT peritoneography is recommended herein to facilitate patient safety and diagnostic reliability of the imaging study.

Peritoneal inflammation and fibrosis in C-reactive protein transgenic mice undergoing peritoneal dialysis solution treatment.

C-reactive protein (CRP) is a mediator of systemic inflammation. Peritoneal dialysis (PD) is known to cause peritoneal inflammation and fibrosis. We compare the degree of peritoneal inflammation and fibrosis in wild-type (WT) and CRP-transgenic (Tg) mice after PD treatment. WT (n = 7) and CRP-Tg (n = 10) C57BL/6 J mice (all male, 10-12 weeks old) were injected intra-peritoneally with 4.25% dextrose PD solution (3 mL/mouse) daily for 28 days, followed by a 2-h peritoneal equilibration test (PET). The mice were then killed. Parietal peritoneal and omental tissues were collected for the assessment of inflammation and fibrosis. After 28 days of PD treatment, CRP-Tg mice had higher dialysate-to-plasma (D/P) creatinine ratio than that of WT mice. Parietal peritoneum of the CRP-Tg mice was more cellular and thicker than that of the WT mice. CRP-Tg mice also had higher connective tissue growth factor (CTGF), intercellular adhesion molecule 1 (ICAM1) and tumor necrosis factor α (TNFα) RNA expressions as well as immunohistochemical staining in the parietal peritoneum than that of the WT mice. CRP-Tg mice have significantly more inflammation and fibrosis than WT mice after PD treatment. Our results suggest that CRP play a role in inflammation and fibrosis induced by PD. The implication of our results to human PD therapy needs further investigations.

High glucose dialysate enhances peritoneal fibrosis through upregulating glucose transporters GLUT1 and SGLT1

Objective: To investigate the role of glucose transporter 1 (GLUT1) and sodium-glucose cotransporter 1 (SGLT1) in high glucose dialysate-induced peritoneal fibrosis. Methods: Thirty six male SD rats were randomly divided into 6 groups (6 in each):normal control group, sham operation group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorizin group (PD+Z group), PD+phloretin+phlorizin group (PD+T+Z group). Rat model of uraemia was established using 5/6 nephrotomy, and 2.5% dextrose peritoneal dialysis solution was used in peritoneal dialysis. Peritoneal equilibration test was performed 24 h after dialysis to evaluate transport function of peritoneum in rats; HE staining was used to observe the morphology of peritoneal tissue; and immunohistochemistry was used to detect the expression of GLUT1, SGLT1, TGF-β1 and connective tissue growth factor (CTGF) in peritoneum. Human peritoneal microvascular endothelial cells (HPECs) were divided into 5 groups:normal control group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorezin group (PD+Z group), and PD+phloretin+phlorezin group (PD+T+Z group). Real time PCR and Western blotting were used to detect mRNA and protein expressions of GLUT1, SGLT1, TGF-β1, CTGF in peritoneal membrane and HPECs. Results:In vivo, compared with sham operation group, rats in PD group had thickened peritoneum, higher ultrafiltration volume, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly increased (all P<0.05); compared with PD group, thickened peritoneum was attenuated, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly decreased in PD+T, PD+Z and PD+T+Z groups (all P<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in peritoneum were positively correlated with the expressions of TGF-β1 and CTGF (all P<0.05). In vitro, the mRNA and protein expressions of GLUT1, SGLT1, TGF-β1, CTGF were significantly increased in HPECs of peritoneal dialysis group (all P<0.05), and those in PD+T, PD+Z, and PD+T+Z groups were decreased (all P<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in HPECs were positively correlated with the expressions of TGF-β1 and CTGF (all P<0.05). Conclusion: High glucose peritoneal dialysis fluid may promote peritoneal fibrosis by upregulating the expressions of GLUT1 and SGLT1.

Peritoneal metastases from mucinous endocervical adenocarcinoma

Pseudomyxoma peritonei is a clinical condition characterized by mucinous tumors and mucinous ascites that accumulates in large volume and over time will interrupt gastrointestinal function. Pseudomyxoma peritonei most commonly arises from a mucinous neoplasm of the appendix (Sugarbaker et al., 1996). Also, occasionally this syndrome may arise from the colon or rectum, gallbladder, small intestine, ovarian teratoma, lung, breast, pancreas, fallopian tube, and urachus (Sugarbaker, 2012a). Described here are three patients presenting with mucinous peritoneal metastases arising from an adenocarcinoma of the endocervix. This cause of this rare condition is unclear; it may be caused by retrograde menstruation. Evaluation of these patients for cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) at a peritoneal surface oncology treatment center early in the natural history of the disease is recommended. Patient presentation 1 A 33 year old woman presented in May of 2011 with chief complaints of abdominal distention and pain. A past history of cone biopsy of the cervix in 2002 showed pre-cancerous cells with no invasive malignancy. CT of the chest, abdomen, and pelvis showed a large volume of intraabdominal fluid consistent with combined mucinous and serous ascites (Fig. 1). Laparoscopy was performed showing bilateral adnexal masses, copious mucinous fluid, and peritoneal metastases on the abdominal wall, the right hemidiaphragm, and greater omentum. Pathology showed mucinous adenocarcinoma and immunostains suggested a cervical origin with P16 and CK7 positive and CK20 negative. Fig. 1 Abdominal and pelvic CT on a patient with adenocarcinoma of the endocervix. Paracentesis resulted in the drainage of 10 l of ascites. Upper and lower gastrointestinal endoscopy was not revealing of a cancerous process. She underwent a 9-hour complete CRS with greater omentectomy, appendectomy, right upper quadrant peritonectomy, lesser omentectomy, pelvic peritonectomy, hysterectomy, and bilateral salpingo-oophorectomy (Sugarbaker, 2012b). Pathology showed in-situ and invasive mucinous adenocarcinoma of the endocervix with metastases to ovaries, fallopian tubes, omentum, and peritoneum. The appendix was normal except for overlying extracellular mucin. She was treated with HIPEC and early postoperative intraperitoneal chemotherapy (EPIC) (Sugarbaker, 2012b). The patient was treated with a single cycle using cisplatin (50 mg/m2) and doxorubicin (15 mg/m2) by intraperitoneal administration at 42 °C. Continuous infusion intravenous ifosfamide was given over the 90 min of HIPEC. Fifteen minutes prior to infusion 2-mercaptoethane sulfonate NA (MESNA) at 260 mg/m2 was given as a bolus. The MESNA was repeated at 4 and 8 h after initiation of the HIPEC. Early postoperative intraperitoneal chemotherapy (EPIC) with paclitaxel at 20 mg/m2 in one liter of 1.5% dextrose peritoneal dialysis solution was used postoperative days one through five (Sugarbaker, 2012b). Systemic chemotherapy was given over five months using paclitaxel at 135 mg/m2 administered over 24 h on day one plus cisplatin 50 mg/m2 administered on day two. Treatment was every 21 days for six cycles. She remains asymptomatic on 6 monthly CT follow-up at 3 years.

Pharmacokinetic and phase II study of heated intraoperative intraperitoneal melphalan

Peritoneal surface malignancy resulting from local dissemination is a common manifestation of treatment failure of gastrointestinal cancers. Although the management of carcinomatosis has been improved with an aggressive surgical approach of extensive cytoreduction followed by heated intraoperative intraperitoneal chemotherapy, no patients are cured when there is residual disease after surgery. Melphalan (L-phenylalanine mustard) is a well-known antineoplastic alkylating agent which has markedly increased pharmacological activity with heat. The use of heated intraoperative intraperitoneal melphalan may provide a pharmacokinetic and clinical advantage in this group of gastrointestinal cancer patients who cannot be made cancer-free with cytoreductive surgery. Thirteen patients with residual disease following cytoreductive surgery for peritoneal carcinomatosis were included in this study. After surgical resection and prior to anastomotic reconstruction, patients received intraperitoneal melphalan (70 mg/m2) in 3 l of 1.5% dextrose peritoneal dialysis solution at 41-42 degrees C for 90 min. Concentrations of melphalan were assessed in the peritoneal fluid, blood, urine and tumor nodules using high-performance liquid chromatography. During the 90 min of treatment 87.2 +/- 4.3% of the drug was absorbed from the perfusate/peritoneal fluid and 11.9 +/- 2.1% was excreted in the urine. The area-under-the-curve ratio of peritoneal fluid to plasma was 33.3 +/- 11.8 with an average peak plasma concentration of 0.82 +/- 0.24 microg/ml occurring at 28.5 +/- 13.1 min. Concentrations of melphalan in tumor nodules on the peritoneal surface were approximately ten times higher than in plasma with an average peak concentration of 7.2 +/- 4.2 microg/gm. The grade III/IV morbidity was 38%; there was no mortality. Approximately 90% of the drug was absorbed during the 90-minute procedure with a 30 times greater exposure of drug at the peritoneal surfaces than in the blood. Concentrations of the drug in peritoneal surface tumor nodules were approximately ten times greater than concentrations in the blood. These data demonstrate that heated intraoperative intraperitoneal melphalan could have a significant impact on the treatment of peritoneal surface malignancies.

Pharmacokinetic changes induced by the volume of chemotherapy solution in patients treated with hyperthermic intraperitoneal mitomycin C

The rationale supporting the use of intraperitoneal chemotherapy in peritoneal surface malignancy relates to a large local-regional effect and low systemic toxicity. While optimizing the use of this treatment strategy, little information regarding the effect of volume of chemotherapy solution is available. The goal of this study was to provide data regarding the effect of volume of chemotherapy solution on the pharmacokinetics of intraperitoneal chemotherapy. Data by which to optimally adjust this parameter during intraperitoneal chemotherapy treatments were sought. Forty-eight patients with peritoneal surface malignancy were treated with hyperthermic intraperitoneal mitomycin C chemotherapy after a complete cytoreduction to remove all visible evidence of mucinous tumor. The dose of mitomycin C was always 12.5 mg/m(2) in males and 10 mg/m(2) in females. The first 12 patients were treated with 6 l of 1.5% dextrose peritoneal dialysis solution. The next 14 patients were treated with 4 l of fluid and then ten patients were treated with 2 l. In the last 12 patients the volume of fluid was 1.5 l/m(2) . Blood, peritoneal fluid, and urine samples were obtained every 15 min for 90 min; additional blood and urine samples were obtained at 120 min. Mitomycin C concentrations, urine volumes, and final intraperitoneal fluid volume were obtained. The intraperitoneal and the plasma concentrations were highest in the 2-l group, less in the 4-l group, and least in the 6-l group. All differences were statistically significant. Also, the percent of mitomycin C absorbed decreased significantly from 2, to 4, to 6 l of fluid. The area under the curve (AUC) ratio of intraperitoneal concentration times time to intravenous concentration times time was 27.01+/-4.92 for 2 l, 22.22+/-7.95 for 4 l, and 24.01+/-8.46 for 6 l. These differences were not statistically significant. If both the volume of chemotherapy solution and the total dose of mitomycin C were determined from the body surface area, the pharmacokinetics of intraperitoneal mitomycin C were more consistent. In order to prescribe a uniform treatment for patients receiving hyperthermic intraperitoneal mitomycin C, the total dose of the drug and the total volume of chemotherapy solution should be determined from the body surface area. If the volume of chemotherapy solution is not based on patient body surface area, predictions regarding toxicity are less precise.

Avoiding Carcinogen Exposure With Intraperitoneal Paclitaxel

Diethylhexylphthalate (DEHP) is a lipid-soluble plasticizer commonly used in the manufacture of polyvinyl chloride- (PVC-) based plastics. Previous studies have documented the leaching of DEHP from PVC-based containers and extension sets during the IV administration of paclitaxel. Study of the leaching of DEHP from infusion bags and peritoneal dialysis solution transfer sets and clinical study of DEHP was proposed. The experiments were performed in a laboratory with plastic ware normally used for intraperitoneal chemotherapy delivery. Samples were taken from fluids that had been in contact with the plastic ware. Also, blood, peritoneal fluid, and urine were collected from a patient. In a controlled laboratory environment, the authors used an established high-performance liquid chromatography assay to determine the rate and extent of DEHP leaching from infusion bags and in the solution transfer set used for early postoperative intraperitoneal chemotherapy (EPIC) administration of paclitaxel. Paclitaxel was tested at a concentration of 40 mg/L to simulate the median dose used for EPIC. In a single patient receiving 34 mg paclitaxel in 1 liter of 1.5% dextrose peritoneal dialysis solution (Dianeal), the presence and concentration of DEHP in samples of peritoneal fluid and urine were determined during the first 24-hour EPIC administration. DEHP levels in fluids exposed to plastic ware and in the patients blood, peritoneal fluid, and urine were determined. The in vitro studies showed that a solution of 40 mg paclitaxel dissolved in a 1 liter bag of Dianeal resulted in the extraction of approximately 26 mg DEHP over 24 hours. Approximately 2 mg DEHP was leached during the first hour and approximately 1 mg per hour over the following 23 hours. Equivalent results were obtained when 20 mg paclitaxel was dissolved in a 500 ml bag of 6% hetastarch (Hespan) with a leaching of approximately 13 mg DEHP in 24 hours. Using the same paclitaxel concentration, the chronic ambulatory peritoneal dialysis solution transfer tubing with a total capacity of 10 ml produced approximately 2 mg DEHP over 24 hours, of which approximately 0.5 mg was produced during the first four hours. Samples from a single patient showed that immediately prior to administration, a 1 liter bag of Dianeal containing 34 mg paclitaxel had about 3.3 mg DEHP. Approximately 3% (110 mcg) of unchanged DEHP was recovered from the peritoneal fluid at 24 hours. Total DEHP excreted in urine over the 24-hour period was approximately 900 mcg (27%). This study showed that the carcinogen DEHP is leached after preparation of paclitaxel from PVC-based containers and DEHP constantly accumulates in the solution transfer tubing. Unless precautionary steps are taken, DEHP can be transferred to patients receiving intraperitoneal paclitaxel. Steps to minimize patient exposure to DEHP during EPIC with paclitaxel are necessary. In the ideal situation, no DEHP-containing plastic should be used for chemotherapy delivery. If that is not possible, (a) paclitaxel solution should be administered as soon as possible after preparation by the pharmacy, (b) infusion should proceed as rapidly as possible via the Tenckhoff catheter, and (c) the Tenckhoff catheter and extension tubing should be cleared by draining ascites fluid through these tubes prior to subsequent intraperitoneal infusions.

Pharmacokinetics and tissue distribution of intraperitoneal paclitaxel with different carrier solutions

For cancers that have disseminated to peritoneal surfaces, intraperitoneal chemotherapy administration results in high drug concentration locally with low systemic toxicity. Using a rat model we compared the pharmacokinetics and tissue absorption of paclitaxel infused intraperitoneally in two isotonic carrier solutions: 1.5% dextrose peritoneal dialysis solution (peritoneal dialysis solution) and hetastarch (6% hydroxyethyl starch), a high molecular weight solution. A total of 60 Sprague Dawley rats were randomized into groups according to the carrier solution administered. Rats were given a single dose of intraperitoneal paclitaxel (40 mg/m2) in 0.1 ml/g body weight of each carrier solution. Each group was further randomized according to the intraperitoneal dwell period (3, 6, 12, 18 and 24 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and the volume recorded. Blood and tissues were sampled using a standardized protocol. Drug concentrations in peritoneal fluid, plasma, and tissues were determined by high-performance liquid chromatography. Fluid clearance from the peritoneal cavity was lower in the presence of hetastarch than in the presence of peritoneal dialysis solution. The mean volumes remaining in the peritoneal cavity were significantly higher with hetastarch at 18 h (P=0.0079). No excess peritoneal fluid remained with peritoneal dialysis solution at 24 h. Mean plasma paclitaxel concentrations were significantly lower with hetastarch at 3 h (P=0.0079), 12 h (P=0.0079), and 18 h (P=0.0317). The mean total quantity of drug remaining in the peritoneal cavity was significantly greater with hetastarch at 12 h (P=0.0079) and 18 h (P=0.0317). There was a 105% increase in the area under the curve ratio of peritoneal fluid to plasma paclitaxel concentrations with hetastarch (391) vs peritoneal dialysis solution (191). Paclitaxel concentrations were significantly greater with peritoneal dialysis solution at 6 h in colon, abdominal wall, and myocardium. The use of intraperitoneal paclitaxel with hetastarch carrier solution provides a pharmacologic advantage for a local-regional killing of residual tumor cells with decreased systemic toxicity. Clinical investigations into the use of 6% hetastarch with high molecular weight chemotherapeutic agents are warranted.

Pharmacokinetics and tissue distribution of intraperitoneal docetaxel with different carrier solutions

Background Intraperitoneal chemotherapy administration results in high drug concentration locally with low systemic toxicity. Using a rat model we compared the pharmacokinetics and tissue absorption of docetaxel infused intraperitoneally in two isotonic carrier solutions; 1.5% dextrose peritoneal dialysis solution (peritoneal dialysis solution) and hetastarch (6% hydroxyethyl starch), a high molecular weight solution. Materials and methods Sixty Sprague–Dawley rats were randomized into groups according to the carrier solution administered. Rats were given a single dose of intraperitoneal docetaxel (80 mg/m 2) in 0.1 ml/g body weight of each carrier solution. Each group was further randomized according to the intraperitoneal dwell period (3, 6, 12, 18, and 24 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and the volume recorded. Blood and tissues were sampled using a standardized protocol. Drug concentrations in peritoneal fluid, plasma, and tissues were determined by high-performance liquid chromatography. Results Hetastarch clearance from the peritoneal cavity was reduced when compared to peritoneal dialysis solution. The mean volumes remaining in the peritoneal cavity were significantly higher with hetastarch at 6 h ( P = 0.022) and 12 h ( P = 0.0012). Plasma docetaxel concentrations were similar for both carrier solutions. The mean total amount of docetaxel remaining in the peritoneal cavity was significantly greater with hetastarch at 3 h ( P = 0.0022), 6 h ( P = 0.0043), and 12 h ( P = 0.0023). There was a 39% increase in the area under the curve ratio of peritoneal fluid to plasma docetaxel concentrations with hetastarch (227) versus peritoneal dialysis solution (163). Docetaxel concentrations were significantly greater with hetastarch in colonic tissue at 18 and 24 h, and in gastric tissue at 6, 12, and 18 h. Conclusion The use of intraperitoneal docetaxel with a hetastarch carrier solution provides a pharmacologic advantage for a local-regional killing of residual intraperitoneal tumor cells without increasing systemic toxicity.

A comparison of hetastarch and peritoneal dialysis solution for intraperitoneal chemotherapy delivery

Aim: Intraperitoneal chemotherapy administration results in high drug concentration locally with low systemic toxicity. We compared the pharmacokinetics of paclitaxel infused intraperitoneally in two isotonic carrier solutions, 1.5% dextrose peritoneal dialysis solution (peritoneal dialysis solution) and hetastarch (6% hydroxyethyl starch), a high molecular weight solution.Methods: Twenty patients with peritoneal carcinomatosis were randomized into one of two groups to receive early postoperative intraperitoneal chemotherapy with paclitaxel for 5 consecutive days following cytoreductive surgery. One group (8 patients) received paclitaxel in one litre of peritoneal dialysis solution; the other group (12 patients) received paclitaxel in one litre of hetastarch. Samples of peritoneal fluid and venous blood were taken during the 23h dwell time. Volumes of chemotherapy solution were recorded and concentrations of paclitaxel determined by high performance liquid chromatography.Results: Hetastarch clearance from the peritoneal cavity was reduced when compared to peritoneal dialysis solution. The mean volume of fluid remaining in the peritoneal cavity at 23h was 900ml ±373.7 (SD) with hetastarch, and 285ml (±157.5) with peritoneal dialysis solution (P=0.0022). The mean total amount of paclitaxel in the peritoneal cavity at 23h was 2.597mg (±1.57) with hetastarch and 0.772mg (±0.667) with peritoneal dialysis solution (P=0.0152).Conclusion: These data show that hetastarch increased the exposure of peritoneal surfaces to paclitaxel by increasing the volume of solution with no decrease in drug concentration. Residual tumour cells within the peritoneal cavity may show an increased response to paclitaxel with hetastarch as a carrier solution.

Early quality of life benefits of icodextrin in peritoneal dialysis

Early quality of life benefits of icodextrin in peritoneal dialysis. The impact of new therapies on patient quality of life (QOL) is emerging as an important indicator of the value of these therapies. In patients on dialysis, previous QOL evaluations have focused mainly on comparative approaches between modalities, or on longitudinal trends within a modality, but few have evaluated technical innovations or introduction of new therapies. The aim of the present study was to assess the early effects of a new dialysis solution (icodextrin) on the QOL of peritoneal dialysis patients. The QOL is compared with that of patients on dextrose, and the impact of demographic, and clinical characteristics on patients' QOL is examined. The kidney disease quality of life questionnaire (KDQOL) was administered to patients who participated in a phase III double-blind, parallel group, active-controlled trial to evaluate the efficacy and safety of a peritoneal dialysis (PD) solution containing icodextrin in comparison with dextrose PD solution. A total of 93 patients (58 icodextrin, and 35 dextrose) completed the questionnaire at both baseline and after 13 weeks. In addition to patients QOL, patients' demographic and clinical characteristics were recorded at both baseline and 13 weeks. Mean change scores from baseline to 13 weeks of icodextrin patients were substantially higher (> or =5) than dextrose, particularly with respect to general health perception, physical functioning, role-physical, and many KDQOL symptom items such as lack of strength, washed out or drained, lack of appetite, faintness or dizziness, dry skin, cramps after an exchange or treatment, cramps during an exchange or treatment, and muscle spasms or twitching. At 13 weeks, icodextrin patients had significantly improved symptoms, and rated their health in general higher than those patients in the dextrose group. Upon multivariate analysis, icodextrin contributed significantly to the improvement of patients' mental health, general health, and symptoms such as muscle spasms or twitching, cramps during an exchange or treatment, cramps after an exchange or treatment, itchy skin, and faintness or dizziness. Peritoneal dialysis patients treated with icodextrin experienced substantial quality of life improvement at 13 weeks after the start of treatment when compared to dextrose patients. Further research is necessary to determine patients' quality of life over time in a longitudinal study setting.

Does Enalapril Prevent Peritoneal Fibrosis Induced by Hypertonic (3.86%) Peritoneal Dialysis Solution?

Peritoneal fibrosis (PF) is one of the most serious causes of failure in continuous ambulatory peritoneal dialysis (PD). Although the underlying mechanism responsible for the genesis of PF is still unknown, transforming growth factor beta (TGFbeta1) has been shown to be associated with PF. Angiotensin converting enzyme inhibitors have been shown to prevent the stimulating effect of growth factors. The aim of the present study was to investigate the effect of enalapril on peritoneal function and morphology in a rat model of experimental PF. Twenty-one albino Wistar rats were divided into three groups: (1) the control group (C) received 10 mL isotonic saline intraperitoneally (i.p.), (2) the dextrose (Dx) group 10 mL 3.86% dextrose PD solution i.p., and (3) the enalapril-treated group (ENA) 10 cc 3.86% dextrose PD solution i.p. plus 100 mg/L enalapril in drinking water. After 4 weeks, a 1-hour peritoneal equilibration test was performed with 20 mL 2.27% dextrose PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration (UF) volume, and levels of dialysate protein, TGFbeta1, and cancer antigen 125 (CA125) were determined. The parietal peritoneum was evaluated histologically by light microscopy. Administration of enalapril resulted in preserved UF (-0.2 +/- 0.7 mL vs 1.7 +/- 0.3 mL, p < 0.05), protein loss (2.3 +/- 0.5 g/L vs 1.6 +/- 0.2 g/L, p > 0.05), and peritoneal thickness (77 +/- 7 microns vs 38 +/- 5 microns, p < 0.001). D/P urea increased significantly in the Dx group (p< 0.05). Both higher levels of TGFbeta1 (undetectable vs 298 +/- 43 pg/mL, p < 0.001) and lower levels of CA125 in dialysate effluent (0.94 +/- 0.5 U/L vs 0.11 +/- 0.1 U/L, p > 0.05) were determined in the Dx group. These findings show that peritoneal morphology and function tests were dramatically deranged in the Dx group. The same properties were partially preserved in the ENA group. The production of TGFbeta1 was significantly reduced but peritoneal thickness was not completely inhibited. In conclusion, by inhibiting the production of TGFbeta1, enalapril can preserve peritoneal histology, peritoneal function, and remodeling of mesothelial cells.

Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy.

In the past, peritoneal carcinomatosis, regardless of primary tumor type, has always been a lethal condition. Recently, special treatments using cytoreductive surgery with peritonectomy procedures combined with perioperative intraperitoneal chemotherapy have resulted in long-term survival. Appendiceal malignancy with a low incidence of liver and lymph node metastases may be especially appropriate for these aggressive local regional treatments. All patients treated with surgery before January 1999 are included. Patients left with gross residual disease after surgery were not given intraperitoneal chemotherapy, but were later treated with intravenous chemotherapy. The intraperitoneal chemotherapy was given in the perioperative period, starting with mitomycin C at 12.5 mg/m2 for males and 10 mg/m2 for females. For patients whose pathology showed adenomucinosis, intraperitoneal chemotherapy was limited to treatment in the operating theater with heated mitomycin C. Patients with mucinous adenocarcinoma or pseudomyxoma/adenocarcinoma hybrid had, in addition to mitomycin C, five consecutive days of intraperitoneal 5-fluorouracil at 650 mg/m2 instilled in 1-1.5 liters of 1.5% dextrose peritoneal dialysis solution. A complete cytoreduction was defined as tumor nodules <2.5 mm in diameter remaining after surgery. The histopathology categorized the patients as having adenomucinosis, adenomucinosis/carcinomatosis hybrid, or mucinous carcinomatosis. A previous surgical score was used to estimate the extent of previous surgical procedures. The morbidity of treated patients was 27% and the mortality was 2.7%. In a multivariate analysis, prognostic factors for survival included the completeness of cytoreduction (P < .0001), the histopathological character of the appendix malignancy (P < .0001), and the extent of previous surgical interventions (P = .001). Patients with a complete cytoreduction and adenomucinosis by pathology had a 5-year survival of 86%; with hybrid pathology, survival at 5 years was 50%. Incomplete cytoreduction had a 5-year survival of 20% and 0% at 10 years. Cytoreductive surgery and perioperative intraperitoneal chemotherapy can be used to salvage selected patients with peritoneal surface spread of appendiceal primary tumors. Similar strategies for other patients with peritoneal surface malignancy such as peritoneal carcinomatosis from colon or gastric cancer, peritoneal sarcomatosis, or peritoneal mesothelioma should be pursued.

Measurement of Fluid Shift in Capd Patients Using Segmental Bioelectrical Impedance Analysis

To determine, using segmental bioelectrical impedance analysis (BIA), the characteristics of fluid shift of each body segment in continuous ambulatory peritoneal dialysis (CAPD) patients during and after peritoneal dialysis (PD) solution exchange. Observational study with repeated measurements of bioelectrical impedance, which is inversely related to tissue fluid content. Thirteen clinically stable CAPD patients. Bioelectrical impedance was measured at frequencies of 5, 50, 250, and 500 kHz in each body segment four times: (1) before and (2) after drainage of dialysate, and (3) at 1 hour and (4) at 2 hours after exchange of new 1.5% dextrose PD solution. Impedance of both arms was significantly increased at 1 hour post exchange at all frequencies. In the trunk, impedance at all frequencies increased significantly after drainage, decreased significantly at 1 hour post exchange, and then increased again for the next hour without significance. Impedance of both legs showed a decreasing tendency at all frequencies during and after exchange. Net calculated water volume changes between the time before drainage and 2 hours post exchange were -0.5 L in the trunk, -0.25 L in both arms, +0.47 L in both legs, -0.28 L in total. The change in body weight between the time before drainage and 2 hours post exchange was -0.21 kg, on average, and significantly correlated with total net calculated water volume change (p = 0.009). Each body segment of the CAPD patient has its own characteristic pattern of fluid shift in response to PD solution exchange or dwell. Segmental BIA may be a useful tool for understanding the physiological changes in fluid shift in CAPD patients.

Value of scintigraphy in chronic peritoneal dialysis patients

A variety of factors can adversely impact chronic peritoneal dialysis (CPD) as an effective renal replacement therapy for patients with end-stage renal disease. These factors include peritonitis, poor clearances, loss of ultrafiltration, and a variety of anatomic problems, such as hernias, peritoneal fluid leaks, loculations, and catheter-related problems caused by omental blockage. This study reviews our experience with peritoneal scintigraphy for the evaluation of some of these difficulties. From 1991 to 1996, 50 peritoneal scintigraphy scans were obtained in 48 CPD patients. Indications for scintigraphy were evaluated, and the patients were placed into four groups: group I, abdominal wall swelling; group II, inguinal or genital swelling; group III, pleural fluid; and group IV, poor drainage and/or poor ultrafiltration. A peritoneal scintigraphy protocol was established and the radiotracer isotope that was used was 2.0 mCi of 99mtechnetium sulfur colloid placed in two liters of 2.5% dextrose peritoneal dialysis solution. Ten scans were obtained to study abdominal wall swelling, with seven scans demonstrating leaks; six of these episodes improved with low-volume exchanges. Twenty scans were obtained to evaluate inguinal or genital swelling, and 10 of these had scintigraphic evidence for an inguinal hernia leak (9 of these were surgically corrected). One of four scans obtained to evaluate a pleural fluid collection demonstrated a peritoneal-pleural leak that corrected with a temporary discontinuation of CPD. Sixteen scans were obtained to assess poor drainage and/or ultrafiltration. Five of these scans demonstrated peritoneal location, and all of these patients required transfer to hemodialysis. The other 11 scans were normal; four patients underwent omentectomies, allowing three patients to continue with CPD. Peritoneal scintigraphy is useful in the evaluation and assessment of CPD patients who develop anatomical problems (such as anterior abdominal, pleural-peritoneal, inguinal, and genital leaks) and problems with ultrafiltration and/or drainage.

Compatibility of cefazolin and gentamicin in peritoneal dialysis solutions.

The compatibility of cefazolin and gentamicin in fluid commonly used for continuous ambulatory peritoneal dialysis (CAPD) was studied. Five admixtures containing cefazolin (75 mg/L and 150 mg/L) and gentamicin (8 mg/L), alone and in combination, were prepared in 1.5% dextrose peritoneal dialysis solution. Solutions were stored for 48 hours at 4 degrees C, 26 degrees C, and 37 degrees C; aliquots for drug assay were obtained at 0, 4, 8, 24, and 48 hours. HPLC and immunofluorescent assays were used to determine cefazolin and gentamicin concentrations, respectively. The cefazolin and gentamicin concentration changes over the study period did not reach statistical significance. Maximal cefazolin and gentamicin losses (12 and 7 percent of the initial concentrations, respectively) were observed at 48 hours in solutions stored at 37 degrees C. No significant differences in concentration changes were observed between combination solutions and solutions containing either cefazolin or gentamicin alone. Cefazolin and gentamicin, alone or in combination, are compatible for at least 48 hours in CAPD solutions.