Strategies for intra-amniotic administration of fetal therapy in a rabbit model of intrauterine growth restriction.

Intrauterine growth restriction affects up to 10% of all pregnancies, leading to fetal programming with detrimental consequences for lifelong health. However, no therapeutic strategies have so far been effective to ameliorate these consequences. Our previous study has demonstrated that a single dose of nutrients administered into the amniotic cavity, bypassing the often dysfunctional placenta via intra-amniotic administration, improved survival at birth but not birthweight in an intrauterine growth restriction rabbit model. The aim of this study was to further develop an effective strategy for intra-amniotic fetal therapy in an animal model. Intrauterine growth restriction was induced by selective ligation of uteroplacental vessels on one uterine horn of pregnant rabbits at gestational day 25, and fetuses were delivered by cesarean section on GD30. During the five days of intrauterine growth restriction development, three different methods of intra-amniotic administration were used: continuous intra-amniotic infusion by osmotic pump, multiple intra-amniotic injections, and single fetal intraperitoneal injection. Technical feasibility, capability to systematically reach the fetus, and survival and birthweight of the derived offspring were evaluated for each technique. Continuous intra-amniotic infusion by osmotic pump was not feasible owing to the high occurrence of catheter displacement and amnion rupture, while methods using two intra-amniotic injections and one fetal intraperitoneal injection were technically feasible but compromised fetal survival. Taking into account all the numerous factors affecting intra-amniotic fetal therapy in the intrauterine growth restriction rabbit model, we conclude that an optimal therapeutic strategy with low technical failure and positive fetal impact on both survival and birthweight still needs to be found.

Intraperitoneal Oil Application Causes Local Inflammation with Depletion of Resident Peritoneal Macrophages.

Oil is frequently used as a solvent to inject lipophilic substances into the peritoneum of laboratory animals. Although mineral oil causes chronic peritoneal inflammation, little is known whether other oils are better suited. We show that olive, peanut, corn, or mineral oil causes xanthogranulomatous inflammation with depletion of resident peritoneal macrophages. However, there were striking differences in the severity of the inflammatory response. Peanut and mineral oil caused severe chronic inflammation with persistent neutrophil and monocyte recruitment, expansion of the vasculature, and fibrosis. Corn and olive oil provoked no or only mild signs of chronic inflammation. Mechanistically, the vegetal oils were taken up by macrophages leading to foam cell formation and induction of cell death. Olive oil triggered caspase-3 cleavage and apoptosis, which facilitate the resolution of inflammation. Peanut oil and, to a lesser degree, corn oil, triggered caspase-1 activation and macrophage pyroptosis, which impair the resolution of inflammation. As such, intraperitoneal oil administration can interfere with the outcome of subsequent experiments. As a proof of principle, intraperitoneal peanut oil injection was compared with its oral delivery in a thioglycolate-induced peritonitis model. The chronic peritoneal inflammation due to peanut oil injection impeded the proper recruitment of macrophages and the resolution of inflammation in this peritonitis model. In summary, the data indicate that it is advisable to deliver lipophilic substances, like tamoxifen, by oral gavage instead of intraperitoneal injection. IMPLICATIONS: This work contributes to the reproducibility of animal research by helping to understand some of the undesired effects observed in animal experiments.

Repeated Intraperitoneal Administration of Low-Concentration Methylcellulose Leads to Systemic Histologic Lesions Without Loss of Preclinical Phenotype.

Methylcellulose (MC; 0.5% concentration) is commonly used when evaluating investigational agents for efficacy in preclinical models of disease. When administered by the oral (PO) route, MC is considered a Food and Drug Administration "generally recognized as safe" compound. Yet, there is limited data pertaining to the tolerability and impact on model fidelity of repeated intraperitoneal administration of 0.5% MC. Chronic administration of high-concentration MC (2%-2.5%) has been used to induce anemia, splenomegaly, and lesions in multiple organ systems in several preclinical species. Histopathological findings from a diagnostic pathologic analysis of a single mouse from our laboratory with experimentally induced chronic seizures that had received repeated intraperitoneal administration of antiseizure drugs delivered in MC revealed similar widespread lesions. This study thus tested the hypothesis that chronic administration of intraperitoneal, but not PO, MC incites histologic lesions without effects on preclinical phenotype. Male CF-1 mice (n = 2-14/group) were randomized to receive either 6 weeks of twice weekly 0.5% MC or saline (intraperitoneal or PO) following induction of chronic seizures. Histology of a subset of mice revealed lesions in kidney, liver, mediastinal lymph nodes, mesentery, aorta, and choroid plexus only in intraperitoneal MC-treated mice (n = 7/7). Kindled mice that received MC PO (n = 5) or saline (intraperitoneal n = 6, PO n = 3) had no lesions. There were no effects of intraperitoneal MC treatment on body weight, appearance, seizure stability, or behavior. Nonetheless, our findings suggest that repeated intraperitoneal, but not PO, MC elicits systemic organ damage without impacting the model phenotype, which may confound interpretation of investigational drug-induced histologic lesions. SIGNIFICANCE STATEMENT: Methylcellulose (0.5% concentration) is commonly used when evaluating investigational agents for efficacy in preclinical models of disease. Herein, we demonstrate that repeated administration of 0.5% methylcellulose by the intraperitoneal, but not oral, route results in systemic inflammation and presence of foam-laden macrophages but does not impact the behavioral phenotype of a rodent model of neurological disease.

Establishment of a rat ovarian peritoneal metastasis model to study pressurized intraperitoneal aerosol chemotherapy (PIPAC).

BACKGROUND: pressurized intraperitoneal aerosol chemotherapy (PIPAC), with or without electrostatic precipitation (ePIPAC), was recently introduced in the treatment of peritoneal metastases (PM) from ovarian cancer (OC). Preliminary clinical data are promising, but several methodological issues as well the anticancer efficacy of PIPAC remain unaddressed. Here, we propose a rat ePIPAC model that allows to study these issues in a clinically relevant, reproducible, and high throughput model. METHODS: laparoscopy and PIPAC were established in healthy Wistar rats. Aerosol properties were measured using laser diffraction spectrometry based granulometric analyses. Electrostatic precipitation was accomplished using a commercially available generator (Ultravision™). A xenograft model of ovarian PM was created in athymic rats using intraperitoneal (IP) injection of SKOV-3 luciferase positive cells. Tumor growth was monitored weekly by in vivo bioluminescence imaging. RESULTS: PIPAC and electrostatic precipitation were well tolerated using a capnoperitoneum of 8 mmHg. All rats survived the (e)PIPAC procedure and no gas or aerosol leakage was observed over the entire procedure. With an injection pressure of 20 bar, granulometry showed a mean droplet diameter (D(v,0.5)) of 47 µm with a flow rate of 0.5 mL/s, and a significantly lower diameter (30 µm) when a flow rate of 0.8 mL/s was used. Experiments using IP injection of SKOV-3 luciferase positive cells showed that after IP injection of 20 × 106 cells, miliary PM was observed in all animals. PIPAC was feasible and well supported in these tumor bearing animals. CONCLUSIONS: we propose a reproducible and efficient rodent model to study PIPAC and ePIPAC in OC xenografts with widespread PM. This model allows to characterize and optimize pharmacokinetic and biophysical parameters, and to evaluate the anti-cancer efficacy of (e)PIPAC treatment.

Assessment of Pain Associated with the Injection of Sodium Pentobarbital in Laboratory Mice (Mus musculus).

The AVMA Guidelines for the Euthanasia of Animals considers injection of barbiturates to be an acceptable method of euthanasia in rodents but states there is a potential for pain when administered intraperitoneally. This study examined the potential for pain in mice by assessing visceral pain after intraperitoneal administration and acute pain by using a paw-lick test. Male and female mice (n = 160) intraperitoneally received a euthanizing dose of sodium pentobarbital at a concentration of 5, 50, or 390 mg/mL and were observed for writhing, peritoneum-directed behaviors (PDB), loss of righting reflex, and time to death. Writhing was not observed in any animal. There was no significant difference in the number of mice exhibiting PDB or in the rate of PDB for responders receiving either saline or the 390-mg/mL solution. There was a significant treatment effect on time, with greater concentration and dose resulting in more rapid loss of righting reflex and death. In the second set of experiments, the same solutions were injected subcutaneously into the plantar hindpaw of male and female mice (n = 84). The number of responders, latency until the first lick, and the number of licks per responder were recorded. The number of responders was increased in the 50-mg/mL group; however, there was no difference in latency or the number of licks per responder. These results show that intraperitoneal injection of sodium pentobarbital for euthanasia in mice did not result in increased behavioral signs of pain, and animals lose consciousness more rapidly than the onset of pain seen in the pawlick test. Therefore, although sodium pentobarbital is capable of inducing inflammation, euthanasia through intraperitoneal administration is rapid and does not result in overt signs of pain when compared with injection of saline.

Intraperitoneal administration of aluminium-based adjuvants produces severe transient systemic adverse events in mice.

Vaccines typically come with adjuvants that trigger the innate immune system in order to prepare best possible inflammatory conditions as to allow the adaptive immune system to become activated, generally for the induction of antibodies. The oldest approved and most abundant immunological adjuvants are salts of aluminium, which are also frequently used in animal models of immunisation and allergy desensitization. In rodents, the intraperitoneal administration of aluminium adjuvants is commonly performed and considered safe. In the current investigation, we show that intraperitoneal administration of aluminium adjuvants is associated with a dose-dependent hypothermic reaction within 10 min of the injection. The body temperature of mice dropped as much as 4 °C, and the clinical symptoms included apathy, hunched posture, and piloerection. The temperature normalised and other clinical manifestations disappeared within 60-80 min of the intraperitoneal aluminium injection, which caused strong infiltration of neutrophil and eosinophil granulocytes into the peritoneal cavity, a clinical manifestations typically associated with inflammasome activation. However, the observed reactions to aluminium adjuvants were independent of NALP3, caspase-1, and interleukin-1ß, but dependent on histamine. Hence, aluminium adjuvants may have potential local and systemic side effects, which warrants further investigations into the nature of these side effects, but also into the possible implications on health in man.

The Global End-Diastolic Volume (GEDV) Could Be More Appropiate to Fluid Management Than Central Venous Pressure (CVP) During Closed Hyperthermic Intrabdominal Chemotherapy with CO2 Circulation.

BACKGROUND: Closed hyperthermic intraperitoneal chemotherapy (HIPEC) may increase abdominal pressure and effects of hemodynamic changes due to maintenance hyperthermia. Our aim was to analyze the safety and effectiveness of our closed technique with CO2 circulation in management fluid status and hemodynamic parameters by means of cardiac preload control measured by Global End Diastolic Values (GEDV) and a gas exchanger. MATERIAL AND METHODS: A Pilot Clinical Study that included 18 advanced ovarian cancer patients undergoing citoreductive surgery and HIPEC. We used a closed-perfusion system (PRS Combat®) that includes CO2 circulation and a gas exchanger. Transpulmonary thermodilutions and hemodynamic measurements (PiCCO2®) were performed after citoreductive surgery (Pre-HIPEC); At half time of the HIPEC (Intra-HIPEC); After HIPEC (Post-HIPEC). RESULTS: No significant hemodynamic measurements changes in the three thermodilutions values of Cardiac Index (CI) (p = 0.227), Global End Diastolic Values (GEVD) (p = 0.966), Stroke Volume Variation (SVV) (p = 0,884) and Systemic Vascular Resistance Index (SVRI) (p = 0.082). No correlation between central venous pressure (CVP) and GEDV (Pre-HIPEC: r = 0.164, p = 0.211; Intra-HIPEC: r = 0.015, p = 0.900; Post-HIPEC: r = 0.018, p = 0.890). There was better correlation between GEDV and CI (Pre-HIPEC: r = 0.432, p = 0.071; Intra-HIPEC: r = 0.418, p = 0.074; Post-HIPEC: r = 0.411, p = 0.080). CONCLUSIONS: Closed intrabdominal chemotherapy with CO2 circulation model may be a safe model for HIPEC by means of a gas exchanger. GEDV and its changes significantly correlated to CI, and not observed for CVP. GEDV values may be more appropriate for monitoring cardiac preload, blood loss limitation and to predict changes in intravascular volume status during intraperitoneal chemotherapy.

Characterisation and Safety of Intraperitoneal Perioperative Administration of Antibacterial Agents: A Systematic Review.

Background Intraperitoneal drug administration applies treatment at the site of diseases with gynaecological, urological, or gastrointestinal origin. The objective of this systematic review was to investigate perioperative intraperitoneal administration of antibacterial agents to characterise the drugs used and their safety profile. Methods A protocol was registered at PROSPERO (CRD42016038956). A systematic review was conducted and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A search was performed in PubMed and EMBASE on the 22nd of April 2016. The inclusion criteria were original articles involving at least 5 patients where antibacterial agents were administered intraperitoneally during or after abdominal surgery as prophylaxis or treatment of infection. Languages were limited to English, German, Danish, Norwegian, or Swedish articles. Results 79 studies were included which used a total of 12 different antibacterial classes. Aminoglycosides, 1st and 2nd generation cephalosporins, tetracyclines, and penicillins were most commonly administered intraperitoneally during or after surgery. The antibacterial agent was usually administered intraperitoneally as monotherapy. However, some studies administered combination regimens with heparin or with another antibacterial agent. The most frequent combination was aminoglycosides and lincosamides. In total, 43% of studies lacked information regarding adverse events. The most frequently reported adverse event was discomfort or pain during administration, especially with use of oxytetracycline. Conclusion At least 12 different classes of antibacterial agents have been administered intraperitoneally during or after surgery as prophylaxis or treatment of intraabdominal infections. Intraperitoneal administration seems safe although use of oxytetracycline may cause discomfort or pain.

Studies on the antibody response and side effects after intramuscular and intraperitoneal injection of Atlantic lumpfish (Cyclopterus lumpus L.) with different oil-based vaccines.

Atlantic lumpfish (Cyclopterus lumpus L.) is used as a biological delousing agent for sea lice (Lepeophtheirus salmonis K.) infestations in Norwegian aquaculture. Here, we present a study on the antibody response and vaccine side effects after intramuscular and intraperitoneal injection of lumpfish with two vaccines. Both vaccines contained bacterial antigens from atypical Aeromonas salmonicida A-layer types V and VI, Vibrio anguillarum serotype O1 and Moritella viscosa sp., but one vaccine contained a vegetable oil-based adjuvant, while the other contained a mineral oil-based adjuvant. Intramuscular injection of the mineral oil-based vaccine caused a high acute mortality of fish within 48 hr after immunization. Intraperitoneal injection of the mineral oil-based vaccine resulted in a lower severity of intra-abdominal side effects than the vegetable oil-based vaccine. Intramuscular injection of the mineral oil-based vaccine resulted in a significantly higher antibody response against A. salmonicida when compared to controls and the vegetable oil-based vaccine group. The antibody response was poor against V. anguillarum and M. viscosa for all groups. Our results indicate that intramuscular injection of oil-based vaccines might be feasible for providing immunological protection for Atlantic lumpfish against bacterial diseases, especially atypical A. salmonicida, but more work is required to identity optimal adjuvants.

Injection anaesthesia with fentanyl-midazolam-medetomidine in adult female mice: importance of antagonization and perioperative care.

Injection anaesthesia is commonly used in laboratory mice; however, a disadvantage is that post-anaesthesia recovery phases are long. Here, we investigated the potential for shortening the recovery phase after injection anaesthesia with fentanyl-midazolam-medetomidine by antagonization with naloxone-flumazenil-atipamezole. In order to monitor side-effects, the depth of anaesthesia, heart rate (HR), core body temperature (BT) and concentration of blood gases, as well as reflex responses, were assessed during a 50 min anaesthesia. Mice were allowed to recover from the anaesthesia in their home cages either with or without antagonization, while HR, core BT and spontaneous home cage behaviours were recorded for 24 h. Mice lost righting reflex at 330 ± 47 s after intraperitoneal injection of fentanyl-midazolam-medetomidine. During anaesthesia, HR averaged 225 ± 23 beats/min, respiratory rate and core BT reached steady state at 131 ± 15 breaths/min and 34.3 ± 0.25℃, respectively. Positive pedal withdrawal reflex, movement triggered by tail pinch and by toe pinch, still occurred in 25%, 31.2% and 100% of animals, respectively. Arterial blood gas analysis revealed acidosis, hypoxia, hypercapnia and a marked increase in glucose concentration. After anaesthesia reversal by injection with naloxone-flumazenil-atipamezole, animals regained consciousness after 110 ± 18 s and swiftly returned to physiological baseline values, yet they displayed diminished levels of locomotion and disrupted circadian rhythm. Without antagonization, mice showed marked hypothermia (22 ± 1.9℃) and bradycardia (119 ± 69 beats/min) for several hours. Fentanyl-midazolam-medetomidine provided reliable anaesthesia in mice with reasonable intra-anaesthetic side-effects. Post-anaesthetic period and related adverse effects were both reduced substantially by antagonization with naloxone-flumazenil-atipamezole.

Behavioral, clinical and pathological effects of multiple daily intraperitoneal injections on female mice.

Pharmacological agents are commonly administered to mice through multiple intraperitoneal (i.p.) injections. The i.p. route of administration is usually considered safe, but questions of animal welfare arise when protocols require that multiple injections be given to the same animal. IACUCs must consider the potential risks associated with multiple i.p. injections in order to determine the maximum number of injections an animal can receive within a study protocol, but there are no published studies of such potential risks. The authors investigated the effects of 30 daily i.p. saline injections on the behavior, body condition, weight, fecal corticosterone levels, hematology and pathology of female adult mice. Results indicate that multiple i.p. injections do not cause any ill effects in mice.

Intraperitoneal perfusion chemotherapy with hyperthermia in some malignant ascites.

Intraperitoneal administration of chemotherapeutic drugs with hyperthermia (HIPEC) increases their local effect on malignant peritoneal diseases and reduces systemic cytotoxicity. The most commonly used are cisplatin, doxorubicin, and mitomycin C. A major disadvantage of intraperitoneal chemotherapy is limited penetration of the drug in the tumor lesion depth (1-3 mm). Extended exposure and increased pressure in the abdominal cavity solution increases penetration of the agent into the tumor and hyperthermia has synergy with cytostatic agent on the permeability of cell membranes and metabolism of the drug. Real clinical hyperthermia is achieved at 41 degrees C. Of greatest importance is the concentration of the drug, but crucial for the prognosis is complete cytoreductive surgery. A major disadvantage of the closed technique is the uneven distribution of the perfusion solution in the peritoneal cavity, and the main advantage is better control of the perfusion, keeping of constant hyperthermia of the solution and regular repetition of manipulation, like intravenous chemotherapy. Laparoscopy determines the stage of the tumor process, refines the indications and preoperative selection for HIPEC, monitors the effects of treatment and determines locations for introducing catheters. In the review the results of the inraperitoneal chemotherapy with hyperthermia in gastric, colorectal, ovarian and other cancers are discussed as well as in diffuse malignant peritoneal mesothelioma and others.

Pathological mechanisms of liver injury caused by continuous intraperitoneal injection of silica nanoparticles.

Crystalline silica is well known to induce chronic lung inflammation by inhalation that can progress to silicosis. Recently, we reported that silica nanoparticles (SN) cause more damage to liver instead of lung when they enter the body by intravenous injection. However, this mechanism is still unclear. In the present study, liver damages caused by mesoporous hollow silica nanoparticles (MHSNs) were demonstrated after continuous intraperitoneal injection into mice twice a week for 6 weeks. The administration of MHSNs at 50 mg/kg increased liver injury markers in serum, such as alanine aminotransferase (ALT), inflammatory cytokines interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α). Histological analysis revealed lymphocytic infiltration and silicotic nodular like lesions in liver. Collagen fibers were observed around the silicotic nodular like lesion, and hydroxyproline level in liver was also increased dramatically. We also found that activated kupffer cells (KCs) played a key role in the liver damage caused by SNs similar to alveolar macrophage in the process of silicosis. These suggest that the mechanism of liver damage caused by SNs is in consonance with the occurrence of silicosis. These findings may provide useful information for the further toxicity and bioapplication research of nanoparticles.

Peritoneal oleogranulomatosis after laparoscopic gastric banding.

Laparoscopic adjustable gastric banding is one of the most frequently performed bariatric operations worldwide owing to its low incidence of iatrogenic complications. Peritoneal oleogranulomatosis, a sequelae of mineral oil contact with tissues, has not been reported in the context of bariatric surgery. We present the case of a 52-year-old woman with an incidental finding of peritoneal oleogranulomatosis at laparoscopic cholecystectomy, who had previously undergone laparoscopic gastric banding. A potential mechanism linking the two is postulated and the importance of histological diagnosis highlighted, given the macroscopic resemblance to carcinomatosis peritonei.

Comparative study of grade 3/4 toxicity associated with intraperitoneal chemotherapy administered after primary versus interval surgical debulking in ovarian cancer.

OBJECTIVE: To determine the prevalence of grade 3 or 4 toxicity associated with intraperitoneal (IP) chemotherapy subsequent to primary surgical debulking compared to post-neoadjuvant chemotherapy and interval debulking in advanced ovarian cancer. METHODS: Patients receiving IP chemotherapy from 2006 to 2010 were reviewed. Study cohort was stratified by initial treatment (upfront surgery vs neoadjuvant chemotherapy). The National Cancer Institute toxicity grading scale was used to assess treatment-related toxicities immediately before each cycle. The χ² test was used to check for association between categorical variables. RESULTS: Thirty-three patients received IP chemotherapy after optimal debulking. Sixteen patients had upfront surgery. The total number of IP chemotherapy cycles administered was 134. Significantly, more patients treated with IP chemotherapy after intravenous neoadjuvant chemotherapy experienced fatigue (P=0.038) compared to those treated after upfront surgery. During the course of IP regimen, the patients having upfront surgery tended to experience more grade 3/4 hematologic toxicities (P=0.06) and abdominal pain (P=0.08). Twenty-four (73%) of 33 patients completed all prescribed IP chemotherapy cycles. There was no significant difference between the 2 groups in need for dose reduction or delays, use of paclitaxel on day 8, neurologic/gastrointestinal/metabolic toxicities, and IP port complications. CONCLUSIONS: Intraperitoneal chemotherapy can be given after optimal primary surgery or interval surgery after neoadjuvant chemotherapy with similar toxicity profile. Toxicity data can be used to plan for optimal IP chemotherapy delivery, patient counseling, and ongoing supportive care.

Doxorubicin causes diaphragm weakness in murine models of cancer chemotherapy.

Doxorubicin is a chemotherapeutic agent prescribed for a variety of tumors. While undergoing treatment, patients exhibit frequent symptoms that suggest respiratory muscle weakness. Cancer patients can receive doxorubicin chemotherapy through either intravenous (IV) or intraperitoneal (IP) injections. We hypothesized that respiratory muscle function would be depressed in a murine model of chemotherapy. We tested this hypothesis by treating C57BL/6 mice with a clinical dose of doxorubicin (20 mg/kg) via IV or IP injection. Three days later we measured contractile properties of muscle fiber bundles isolated from the diaphragm. Doxorubicin consistently depressed diaphragm force with both methods of administration (P < 0.01). Doxorubicin IP exaggerated the depression in diaphragm force and stimulated tissue inflammation and muscle fiber injury. These results suggest that clinically relevant doses of doxorubicin cause respiratory muscle weakness and that the loss of function depends, in part, on the route of administration.

[Choose which method for the chemotherapy of epithelial ovarian carcinoma: a meta-analysis].

OBJECTIVE: To evaluate the differences of clinical efficacy between intraperitoneal and intravenous chemotherapy. METHODS: The literature database was extensively searched to retrieve the randomized controlled trials with a relevance of study goal. The strict inclusion and exclusion criteria were formulated. And the original studies were selected. After a quality evaluation, the data were extracted. The Cochrane collaboration Revman 4.2 version software was used for meta-analysis. RESULTS: Five clinical studies were included and there were a total of 1 229 eligible patients. Intraperitoneal chemotherapy and intravenous chemotherapy groups were compared: (1) 2 and 3-year progression-free survival (PFS) increased, 2, 3 and 5-year overall survival (OS) increased. The difference was significant enough so that definite conclusions could be drawn; (2) Among the six indicators of unpleasant chemotherapeutic effects (leucopenia, anemia, thrombopenia, GI tract reactions, neurotoxicity and fever), the occurrence of gastrointestinal reaction increased. The difference was significant enough so that definite conclusions could be drawn. And the remaining five indicators had no statistical significance so that definite conclusions could not be drawn. CONCLUSIONS: For patients with epithelial ovarian cancer (Stages FIGOII-IV) undergoing previously a satisfactory tumor reduction surgery (postoperative residual lesions < 1 to 2 cm), intraperitoneal chemotherapy can improve their 2 and 3-year PFS rates and the 2, 3 and 5-year OS rates; Intraperitoneal chemotherapy has not reduced the side effects. But there is an elevated occurrence of gastrointestinal reactions.

Intraperitoneal access via direct puncture is an alternative way to deliver intraperitoneal chemotherapy in ovarian, fallopian tube and primary peritoneal cancer.

OBJECTIVES: Intraperitoneal (IP) chemotherapy has not been widely accepted in the treatment of ovarian cancer. One of the main reasons is the lack of a convenient and safe way to deliver IP therapy. The objective of this study was to investigate the feasibility of delivering IP chemotherapy via direct puncture using a peripheral venous needle, as well as evaluating the associated risk factors and complications in the primary treatment of ovarian, fallopian tube, and primary peritoneal cancer. METHODS: The clinical records of all patients with stage II-IV epithelial ovarian, fallopian tube, and primary peritoneal cancer at Sun Yat-sen University Cancer Center from 01/1995 to 11/2006 were reviewed retrospectively to identify patients who had received IP therapy via direct puncture after primary cytoreduction. RESULTS: We identified 194 patients, and 121 (62.4%) of them successfully completed six or more cycles of IP chemotherapy, whereas 73 (37.6%) failed. Two (1%) patients ceased IP therapy directly due to IP access related complications and 35 (18.1%) discontinued IP therapy for reasons unrelated to IP access. Old age might be a potential risk factor for IP therapy failure. The IP therapy failure rate in patients over 60 years old was higher than that in patients under or at 60 (57.1% versus 34.3%, P=0.021). Body mass index were not associated with IP therapy failure. CONCLUSIONS: IP access via direct puncture using a peripheral venous needle could be an alternative and safe way to deliver IP chemotherapy in the primary treatment of ovarian cancer.

Fatigue in women receiving intraperitoneal chemotherapy for ovarian cancer: a review of contributing factors.

Women diagnosed with stage III or IV ovarian cancer typically are treated with surgery followed by chemotherapy. Intraperitoneal (IP) chemotherapy, the direct administration of chemotherapy into the IP cavity, has been explored as a viable treatment option for some women with advanced ovarian cancer. Fatigue may occur as a result of the disease process, treatment, or a wide variety of physical, psychological, or situational factors. Fatigue is one of the most common and distressing side effects associated with chemotherapy and it may be intensified in women receiving IP chemotherapy. The purpose of this article is to examine fatigue in women receiving IP chemotherapy for advanced ovarian cancer and to examine what aspects of IP chemotherapy may contribute to fatigue development. Factors reviewed include surgery for debulking the tumor and placement of the IP catheter, administration of IV chemotherapy in addition to IP chemotherapy, pain, anemia, sleep disturbances, gastrointestinal disturbances, and emotional distress. Oncology nurses who are knowledgeable about the factors that contribute to fatigue in women receiving IP chemotherapy will be better prepared to conduct a comprehensive assessment and develop effective treatment strategies.

Chylous ascites: an unusual complication of peritoneal dialysis. A case report and literature review.

Chylous ascites is a rare complication in patients undergoing peritoneal dialysis. It may occur due to traumatic peritoneal dialysis catheter insertion or other causes. It is important to be aware of this condition as it may be confused with peritonitis, and antibiotics may be inappropriately administered. We report a case of chylous ascites occurring after catheter insertion and discuss management of this condition.