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Clinical applicability of the ATP cell viability assay as a predictor of chemoresponse in platinum-resistant epithelial ovarian cancer using nonsurgical tumor cell samples.

OBJECTIVES: There is no basis for choosing one chemotherapy over another in platinum-resistant epithelial ovarian cancer based on published response rates. This study explores the feasibility and accuracy of the ATP cell viability assay (ATP-CVA) in predicting chemoresponse in these difficult situations to choose the most appropriate drug for treatment. METHODS: Predominantly nonsurgical tumor samples for histological proof of recurrence were tested against a panel of drugs for salvage chemotherapy. Clinicians were blinded to the test results. Patient responses were evaluated after a minimum of three cycles of single-agent chemotherapy and correlated with test results. RESULTS: The evaluability rate was 85% (5 of 33 contaminated). The majority (24) were obtained by abdominal paracentesis and trucut biopsy. Of the 28 successful assays, 8 were excluded from analysis because four chose not to have chemotherapy and four withdrew after fewer than three cycles because of unacceptable side effects. The overall response rate to salvage chemotherapy was 15%. The sensitivity was 100% and specificity 82%. Resistance was correctly predicted in 100% and response correctly predicted in 50%. The outcomes of 17 of 20 patients were predicted correctly, giving an accuracy of 85%. CONCLUSIONS: It is feasible to test nonsurgical tumor specimens in recurrent cancer. The ATP-CVA correctly identified a group of patients with a 50% chance of response to salvage chemotherapy. This information may be useful in the decision-making process. A prospective, randomized study will be done to confirm these results.

Adenosine Triphosphate↗

Vascular endothelial growth factor is increased in ascites from metastatic pancreatic cancer.

INTRODUCTION: Vascular endothelial growth factor (VEGF) is an angiogenic factor that increases vascular permeability. VEGF stimulates capillary formation and has mitogenic effects on vascular endothelial cells. The development of malignant ascites causes significant morbidity. We hypothesized that increased levels of VEGF play a role in the development of malignant ascites in patients with pancreatic cancer. METHODS: Athymic mice underwent orthotopic implantation of human pancreatic ductal adenocarcinoma tumors (250,000 cells) into the body of the pancreas. Tumors were allowed to grow for 12 weeks, at which time ascites develops in 50% of mice. Paracentesis was performed on mice with noticeable ascites. Saline lavage was performed in mice with equivalent pancreatic tumor masses without ascites and served as control. Both ascites and tumor masses were harvested for VEGF protein quantitation by ELISA. RESULTS: VEGF protein levels were elevated in malignant ascites by 15-fold compared to control mice with equivalent tumors (N = 6, P < 0.001, t test). VEGF levels were slightly higher in the primary tumor masses harvested from mice without ascites. Mice with ascites also had metastatic nodules throughout the abdominal cavity. CONCLUSIONS: We are reporting for the first time that VEGF levels are increased in the ascites of nude mice with orthotopically transplanted human pancreatic cancers. VEGF increases vascular permeability and allows for extrapancreatic seeding of tumors. Irrespective of primary tumor size, intraperitoneal VEGF levels are increased when ascites and extrapancreatic nodules are present, while a paradoxical decrease is observed in VEGF levels of primary tumors.

Animals↗

Delayed suprachoroidal hemorrhage after penetrating keratoplasty.

We report on an aphakic 30 year-old patient who underwent penetrating keratoplasty on his only functioning eye. On the first day after the operation he developed a total choroidal detachment due to suprachoroidal bleeding. The patient had no sense of orientation. Vision decreased to faulty light perception. One week postoperatively a posterior sclerotomy was performed in order to drain the suprachoroidal blood. Via a paracentesis the globe was pressurized with hyaluronic acid. The following day the suprachoroidal blood had almost disappeared. The retina had become reattached. During a follow-up period of 2 years the visual acuity remained 20/30.

Adult↗

Fine structural studies of ciliary processes after treatment with cholera toxin or its B subunit.

Delivery of 2 micrograms of cholera toxin (CT), a specific, irreversible activator of adenyl cyclase, via the blood causes dilation of capillaries and stromal edema of the ciliary processes. These morphologic changes occur within 3 h, are maximal at 12 to 24 h, then gradually return to normal by 72 h. In the late phase of hypotony, ultrastructural changes in the ciliary epithelia, similar to Greeff vesicles, are due to a "paracentesis effect" from hypotony, caused by decreased aqueous flow through the eye. Delivery of 2 micrograms of the B subunit of CT (Sub-B) causes very mild capillary dilation and stromal edema of ciliary processes. These changes reach their peak at 3 h, then return to normal at 24 h. No significant damage occurred to the pigmented or non-pigmented epithelium with either agent. No hemorrhage, invasion of inflammatory cells or appearance of fibrin exudates in the ciliary processes could be detected.

Animals↗

Role of surgical therapy in management of intractable ascites.

Almost 10% of patients with cirrhosis and ascites develop intractable ascites. When large-volume paracentesis fails to relieve ascites, patients may be submitted to one of the three following surgical options: portosystemic shunting, peritoneovenous shunting, or liver transplantation. Portosystemic shunting is efficient in clearing ascites, but it is associated with a high rate of encephalopathy and liver failure. The indications for portosystemic shunting are therefore limited for treatment of intractable ascites and should be performed only in patients with good liver function in whom all other treatments failed. Peritoneovenous shunting has been associated with a high rate of early complications and valve obstruction. Improvements in perioperative care and in the material used have greatly reduced the operative risks and increased the patency rate. Mortality remains high in patients with severe liver failure or with a history of spontaneous bacterial peritonitis or variceal bleeding. Peritoneovenous shunting should not be done when these risk factors are present. In the absence of such risk factors, peritoneovenous shunting is a good procedure and may provide definitive relief of ascites and long-term survival in more than 50% of the operated patients. In patients with poor risk factors liver transplantation may be preferable, and the onset of intractable ascites in a patient with a severely compromised liver should trigger the indication of liver replacement.

Ascites↗

Klippel-Trenaunay syndrome associated with splenomegaly: report of a case.

We report herein the case of a 19-year-old woman, diagnosed as having Klippel-Trenaunay syndrome at the age of 3 years, who presented to our hospital with severe abdominal pain. Abdominal computed tomography revealed splenomegaly, ascites, and paracentesis confirming an intraabdominal hemorrhage. Thus, an emergency laparatomy was performed for a suspected splenic rupture, and 2.5 L of blood was drained from the abdominal cavity. Splenomegaly was confirmed, and a splenectomy was performed. The patient's postoperative course was complicated by disseminated intravascular coagulation, but she recovered and was discharged 3 weeks following surgery. Pathological examination of the spleen suggested that the splenomegaly was caused by high venous pressure due to splenic vein stenosis. To our knowledge, this is the first reported case of Klippel-Trenaunay syndrome associated with marked splenomegaly.

Adult↗

Cilia in the ciliary epithelium.

Cilia in the pigmented and nonpigmented ciliary epithelial cells were studied by electron microscopy in the normal Rhesus monkey eye. In addition cilia formation was studied following paracentesis as well as injection of hemoglobin into the vitreous cavity. In all eyes studied, cilia had a 9 + 0 microtubule pattern; however, some cilia had aberrant arrangement of microtubules. Cilia increased in number and showed elongation in the treated eyes, these newly-formed cilia occasionally extending towards the cell interior opposite to the normal orientation. The results suggested that the formation of ciia can be provoked by a variety of experimental stimuli either with or without drugs.

Animals↗

Penetration of ocular compartments by tetracyclines. I. An experimental study with tetracycline.

Total antibiotic concentration of tetracycline hydrochloride was determined in the ocular structures of rabbits by radioactive tracer method. Concentration of tetracycline of 0.1 to 5 microgram/g, adequate to inhibit the growth of bacteria of high or medium susceptibility, was measured from all ocular structures with the exception of the lens. Tetracycline concentration in the aqueous humor was inferior to that in the vascularized ocular tissues and to that in the cornea. Vitreous body tetracycline level, about 0.3 microgram/g, was about half of the concentration in the aqueous humor. The disruption of the blood-aqueous barrier following paracentesis led to an immediate increase of tetracycline concentration in the anterior structures of the eye.

Animals↗

Primary lymphatic dysplasia in children: chylothorax, chylous ascites, and generalized lymphatic dysplasia.

Primary lymphatic "dysplasia", a congenital maldevelopment, interferes with function of the lymphatic system and causes effusion of chyle or lymph into the limbs and pleural or peritoneal cavity. Between 1955 and 1982, 38 Mayo Clinic patients were found to have a chylous effusion or dysplasia of the lymphatic system. In 22, the condition was secondary to surgery or other medical problems and in 16 it was primary. These cases were separated into three categories: chylothorax, chylous ascites, and generalized lymphatic dysplasia. Conservative therapy, such as a restricted fat diet or total parenteral nutrition with repeated thoracentesis or paracentesis, was effective in the children with isolated abnormalities of the lymphatic system (75% resolution rate, no deaths). All five children with documented generalized dysplasia reported in the literature had died; of the three reported here, one has died and two have become progressively worse.

Adolescent↗

Studies on the "vascular labeling" phenomenon in the iris and the ciliary body of the rat after intravenous injection of colloidal carbon.

The occurrence of carbon deposits after intravenous injection of colloidal carbon (vascular labeling phenomenon) in the iris and the ciliary body of the rat eye was studied by vital microscopy, unstained perfused mount preparations, and by electron microscopy. Generally in the untouched eye the vascular labeling phenomenon is either absent or appears only in the form of finest granular deposits in some capillaries and venules of the iris and the ciliary body. A decrease of intraocular pressure by paracentesis causes a certain blackening phenomenon, which prefers the capillaries and the venules of the iris and the capillaries in the ciliary processes. This effect is intensified by a further decrease of the intraocular pressure to -30 mm Hg. Predominantly the deposits are found stronger in the ciliary region than in the iris. Increase of the intraocular pressure of up to 30 mm Hg diminishes the blackening phenomenon. After administration of the vasodilator bencyclane into the anterior chamber the vascular labeling phenomenon shows a clear graduation of carbon affinity depending upon the concentration of the drug: The capillaries and venules are exclusively blackened at low concentrations, additionally the collecting venules and arterioles are influenced at medium and high doses. By electron microscopy an intraluminal as well as an intramural (subendothelial) deposition of carbon, partly accompanied with signs of hemoconcentration, can be seen. Extravascular position of carbon material is seldom observed and restricted to a state of abnormally high vascular permeability. The observations give evidence for a 'gradient of permeability' between the different types of vessels of the terminal anterior uveal vascular system and also permit the assumption that the vessels of the ciliary processes are more permeable than those of the iris.

Animals↗

Internal ablative sinostomy using a fiber delivered Q-switched CTE: YAG laser (2.69 microns).

Current trends of laser technology towards low-thermal photoablative pulsed mid-infrared lasers open new, more adequate approaches to experimental surgical procedures which have already been evaluated in the past. Transcorneal laser ablation of the trabecular meshwork (internal sinostomy) in human autopsy eyes was performed with a Q-switched CTE:YAG laser (wavelength: 2.69 microns, pulse width: 1 microsecond). Beam delivery was achieved with conventional optical quartz fibers (Low-hydroxy-fused-silica: 0.3 ppm, 50 cm length, 200 microns diameter). Light- and scanning-electron-microscopy were used for histological examination and micromorphological analysis. By applying two laser pulses (6 J/cm2) to the functional trabecular meshwork, a round sinostomy with a diameter corresponding to the diameter of the fiber-tip was achieved. It was possible to set several internal sinostomies into the chamber angle opposite to the entering paracentesis of the laser fiber-tip. Collateral thermal tissue alteration reached up to 50 microns, and since fiber-tip contact was maintained during laser application, thermal tissue alteration was also found around the opposite wall of Schlemm's canal. At higher energy fluences mechanical (disruptive vaporization) effects were significantly enhanced. It can be concluded, that low-thermal pulsed mid-infrared lasers are adequate instruments to perform transcorneal trabecular ablation (abinterno sinostomy). The laser used in this study (CTE:YAG) bears the advantage that its radiation can easily be delivered in conventional optical quartz fibers.

Fiber Optic Technology↗

Pancreatic ascites: diagnostic importance of ascitic lipase.

10 cases of pancreatic ascites are presented. Ascitic fluid lipase is complementary to the determination of ascitic amylase in the diagnosis of pancreatic ascites and may be a more reliable diagnostic indicator of pancreatic ascites on a random ascitic fluid sample. Conservative management, consisting of abdominal paracentesis with or without diurectics, proved to be the treatment of choice in 3 of our patients who failed to reveal an associated pseudocyst.

Adenocarcinoma↗

Myxedema ascites.

A 74-year-old man presented with mental obtundation and massive ascites without evidence of significant impairment of liver function. Thyroid function studies suggested hypothyroidism. Aspirated ascitic fluid had the characteristics of an exudate. Thyroid replacement therapy resulted in rapid clinical improvement with resolution of the ascites. Prompt recognition of myxedema ascites may prevent the inappropriate use of diuretic agents, therapeutic paracentesis, and sometimes unnecessary laparotomy.

Aged↗

Biochemical studies in peritoneal fluid from patients with acute pancreatitis. Relationship to etiology.

The levels of pancreatic digestive enzymes, lysosomal hydrolases, and protease inhibitors were evaluated in ascites fluid from 24 patients with acute pancreatitis diagnosed as alcoholic, gallstone-induced, or idiopathic. In this group the concentrations of amylase (354 +/- 98 ng/ml), immunoreactive cationic trypsinogen (1840 +/- 238 ng/ml), and immunoreactive elastase 2 (1492 +/- 262 ng/ml) were greatly elevated in comparison to the corresponding serum values. Enzyme levels in ascites from the idiopathic pancreatitis group tended to be higher than the levels from the other two groups. Activity of acid phosphatase and beta-glucuronidase was significantly higher in ascites compared to serum in all groups. On the other hand, levels of immunoreactive alpha 1-protease inhibitor and alpha 2-macroglobulin in ascites fluid were about half the average concentrations reported for normal serum. Significant amounts of tryptic amidase activity (61.7 +/- 13.7 micrograms/ml) were observed, indicating a trypsin-alpha 2-macroglobulin complex. These data indicate an imbalance in the protease-to-inhibitor ratio in ascites fluid from patients with acute pancreatitis. Coupled with elevated ribonuclease activity (27.4 +/- 3.4 units), a positive methemalbumin test in 23 of 24 patients (1.1 +/- 0.4 mg hematin/100 ml), and an average protein concentration of 4.0 +/- 0.2 g/100 ml, these observations demonstrate that abdominal paracentesis and the biochemical analyses of ascites fluid provide useful information related to the biochemical events in acute pancreatitis and may be useful in the diagnosis of difficult cases, but their predictive value of severity remains to be established.

Acute Disease↗

Analysis of ascitic fluid in cirrhosis.

In order to determine the composition of "normal" ascitic fluid, the results of analysis of the first paracentesis on 347 consecutive cirrhotic patients with ascites at the West Haven Veterans Administration Hospital between 1955 and 1976 were examined. The ascites was considered "normal" in 259 patients. Bacterial peritonitis was present in 51, malignant ascites in 18, pancreatitic ascites in 15, and ascites of other types in 4 patients. Normal ascites is sterile, usually clear, and contains 281 +/- 25 leukocytes/mm3 (mean +/- SEM), 27 +/- 2% of which are polymorphonuclear. In spontaneous bacterial peritonitis the fluid is usually cloudy, contains 6084 +/- 858 white blood cells/mm3, 77 +/- 4% of which were PMN and culture is positive for a single bacterial species, usually enteric in origin. Malignant and pancreatitis ascites are sterile, often cloudy, and contain an average of 696 +/- 273 and 1821 +/- 833 leukocytes/mm3, respectively, about half of which are polymorphonuclear. Amylase activity is increased in pancreatitic ascites, but not in other types of ascites. Stained smears of sediment for bacteria are often positive in bacterial peritonitis, but not in the other categories. Neither the specific gravity, protein concentration, nor glucose level is useful in the differential diagnosis of ascites. Based on the critical number of leukocytes alone, (500/mm3), one can accurately differentiate infected from uninfected fluid in over 90% of ascitic patients.

Amylases↗

Continuous ascitic recirculation in severe ovarian hyperstimulation syndrome.

Massive ascites, hydrothorax, acute renal failure and thromboembolism are clinical manifestations of severe ovarian hyperstimulation syndrome (OHSS) which may complicate the induction of ovulation with exogenous gonadotrophins. We report a case of severe OHSS with ascites formation in excess of five litres per day. Massive ascites and bilateral pleural effusions resulted in respiratory failure. Continuous ascitic recirculation (AR) was commenced after repeated paracentesis and i.v. fluid therapy failed to improve the patient's condition. The procedure was undertaken for a total of 15 days and rapidly resulted in marked improvement of impaired respiratory function. Febrile episodes occurred on 3 occasions, but we did not observe coagulation disturbances or adverse haemodynamic effects. Continuous AR is a safe and effective treatment of complicated severe OHSS.

Adult↗

Chylous ascites: total parenteral nutrition as primary therapeutic modality.

A female infant with Down syndrome and congenital chylous ascites presented at birth with respiratory distress secondary to marked abdominal distension. Total parenteral nutrition (TPN) and paracentesis were the primary therapeutic modality. On hyperalimentation, however, ascites initially recurred, requiring additional paracenteses to improve respiratory distress. The chylous ascites, lymphopenia and hypoalbuminemia were relieved after 10 weeks of TPN administration. We recommend a long-term course (10 weeks) of TPN before an exploratory laparatomy and possible surgical intervention are considered.

Chylous Ascites↗

Pseudoascites: unusual presentation of omental cyst.

An unusual case of omental cyst is described. The child initially presented with a unilocular intraperitoneal fluid collection on CT. After paracentesis, CT showed freely layering peritoneal fluid, with eventual complete resolution of fluid. CT eight months later demonstrated re-appearance of a multi-septated cystic mass. At surgery, an omental cyst was found.

Ascites↗