Diagnostic Dilemma: A Case Report on Primary Peritoneal Carcinoma in a Patient with Suspected Ovarian Malignancy

@#INTRODUCTION: Primary peritoneal carcinoma (PPC) is an uncommon malignancy and is often misdiagnosed as peritoneal carcinomatosis from metastatic gastrointestinal carcinoma and more frequently from ovarian carcinomas due to a common embryonic origin of the ovary and the peritoneum. Its diagnosis is a challenge for clinicians. Herein, we report a rare case of PPC in a 72-year-old woman who was initially suspected with metastatic ovarian malignancy, and emphasizes points that help differentiate PPC from primary ovarian cancer. CASE: This a case of a 72-year-old female with abdominal discomfort and distension, initially diagnosed with ovarian carcinoma, with abdominal CT scan revealing thickening of the omentum multiple enhancing nodules in the left adnexa, within the pouch of Douglas and subdiaphragmatic region compatible with malignancy such as metastases from carcinoma. Cancer antigen (CA) 125 (3476 u/mL) and CA 15-3 (45.94 u/mL) were elevated. The patient underwent dilation and curettage and diagnostic laparoscopy and biopsy with frozen section, which revealed metastatic clear cell adenocarcinoma, favoring primary ovarian carcinoma. The patient then underwent exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy with bilateral lymph node dissection, and omentectomy. Further histopathological findings later confirmed that the patient had carcinoma primarily from the peritoneum instead of from the ovary. The patient was discharged, improved and underwent chemotherapy post-operation. CONCLUSION: This report emphasizes how to distinguish primary malignancy from the peritoneum from that in the ovary, preventing misdiagnosis. The emphasis in considering primary peritoneal cancer as a differential diagnosis in patients with abdominal symptoms suspected due to malignancy should be noted.

Glutathione S-transferase and metallothionein levels in the freshwater prawn Macrobrachium malcolmsonii exposed to mercury.

Healthy juveniles of M. malcolmsonii were exposed to 24.1 <g l-1 of mercury (96 hr LC50: 145 <g l-1 Hg) for a period of 21 days. The hepatopancreas and gills of the prawns were sampled on 8th, 15th and 22nd day of exposure. Accumulation and elimination of Hg, activity of glutathione S-transferase (GST), content of glutathione (GSH) and metallothionein (MT) level were studied. Mercury accumulation was found to be higher in the hepatopancreas (88.60 <g g-1) and lower in the gills (67.8 <g g-1). However, Hg elimination was found to be faster in the gills (62%) and slower in the hepatopancreas (58%). Therefore, the rate of Hg elimination did not match the rate of its uptake. The activity of GST was found to be higher in tissues of test prawns (5.94-9.13 nmol mg-1 protein min-1) on all sampling days when compared with controls (3.45-4.23 nmol mg-1 protein min-1). Similarly, the content of GSH was found to be higher in tissues of test prawns (0.80-1.43 <mol g-1 protein) on all sampling days when compared with controls (0.55-1.00 <mol g-1 protein). These results indicate the formation of glutathione conjugate in test prawns to eliminate Hg. The induction of MT level was also found to be higher in tissues of test prawns (57.50-75.76 nmol g-1 protein) on all sampling days when compared with control (20.24-45.22 nmol g-1 protein). This indicates the fact that sequestration of Hg has occurred for its easy elimination. Thus, induction of GST-GSH and MT ensured protection and adaptation of test prawns to thrive in Hg contaminated environment.

Sub-lethal impact of carbaryl on food utilization in the freshwater prawn Macrobrachium malcolmsonii.

This study determines the toxic effect of carbaryl (Sevin® 50% W.P) on the food utilization parameters in intermoult juveniles of the prawn, Macrobrachium malcolmsonii. The prawns (4.5-5.0 cm in length and 1.0- 1.25 g wet wt.) were exposed to three sub-lethal concentrations of carbaryl (5.15, 7.73 and 15.47 μg l-1) for duration of 40 days. The toxic medium was renewed daily. The prawns were fed ad libitum with known energy quantity of boiled goat liver on daily basis. The overall wet weight gain was calculated. The energy lost through unconsumed food (15-60%), faeces (15-109%), ammonia excretion (9-27%) and moults (13-26%) of the prawns were calculated. The feeding rate, the rate and efficiency of absorption, the metabolic and food conversion rates and the gross and net food conversions efficiencies were found to be significantly declined (p<0.05) in test prawns when compared to that of the control. The energy lost through faeces, ammonia excretion and exuvia was found to be significantly elevated (p<0.05) in test prawns than that of the control. The effect of carbaryl on the bioenergetics parameters was severe in the highest sub-lethal concentration, less in the intermediate concentration and least in the lowest sub-lethal concentration. The results indicated that decrease in feeding, absorption, metabolism and food conversion are interdependent and toxicity of carbaryl diverting energy from production to maintenance pathways, which ultimately resulting in declined growth of M. malcolmsonii.

Ultrastructural observations in gills and hepatopancreas of prawn Macrobrachium malcolmsonii exposed to mercury.

The juveniles of M. malcolmsonii were exposed to 24.1 µg l-1 of Hg for a period of 21 days. The gills and hepatopancreas of test prawns were sampled and processed for electron microscopic observations. Mitochondria are the organelle most affected in the gills of test prawns. The number of mitochondria and the electron-density of the matrix were found to be less in test prawns. The in-folding of cell membrane associated with mitochondria was absent in test prawns. This suggests that operation of the mitochondrial pumps was affected in the gills of test prawns. Vacuoles with crystalline granular inclusions were noted in the gills of test prawns. These are suggestive of metal-rich inorganic deposits or granules representing detoxified dumps of Hg. In the hepatopancreas of test prawns, the tubules exhibit vacuoles with granular inclusion and the cell cytoplasm contains electron-dense granules, which indicate a storage detoxification of Hg. The mitochondria were shrunken in the hepatopancreas of test prawns. This suggests attenuation of its function. The rough endoplasmic reticulum appeared vesiculated and dilated. These reactions denote the hyperactivity of the rough endoplasmic reticulum. Membranous whorl-like structures with myelin fibers and residual bodies were seen in the hepatopancreas of test prawns. Such structures indicate the involvement of lysosomal breakdown in detoxification process. The ultrastructural alterations are suggestive of the operation of compensatory mechanisms within the test prawns to enable it to tolerate Hg toxicity. However, these alterations would have an impact on the cellular integrity of the gills and hepatopancreas and such alterations can be taken as ‘biomarkers’ for assessing Hg pollution in the aquatic environment.

Manifestation of carbaryl toxicity on soluble protein and histopathology in the hepatopancreas and gills of the prawn, Macrobrachium malcolmsonii.

The present study examined alterations in the protein pattern and histopathology of the hepatopancreas and gills of Macrobrachium malcolmsonii following exposure to Sevin®, the commercial grade of carbaryl (1-Naphthylmethyl carbamate) pesticide. Juvenile prawns were exposed to sub-lethal concentrations 5.15 'g l-1, 7.73 'g l -1and 15.47 'g l -1of carbaryl for 21 days. Samples were obtained from the hepatopancreas and gills of prawns. The concentration of buffer soluble protein in tissues of test prawns was significantly (p<2.5%) lower than the control. This suggests that proteins were utilized to generate energy in order to withstand carbaryl induced toxic stress. Polypeptide bands of different molecular mass (150 - 10 kDa) in tissues of test prawns stained less intensely than those in control. This indicates that carbaryl toxicity caused protein degradation in tissues of test prawns. The histology of the hepatopancreas and gills showed few marked pathological changes in prawns exposed to carbaryl. These include rupture of the basal laminae, abnormal infiltration / aggregation of hemocytes in the interstitial sinus of the hepatopancreas and in the hemocoelic space of gill lamellae, fused gill lamellae and necrosis like appearance both in the tubules of the hepatopancreas and gill lamellae. The structural alterations observed in the hepatopancreas and gills of the prawns suggest that carbaryl caused tissue damage in M. malcolmsonii. Protein degradation is a phenomenon in damaging tissues, and thus, under such condition the hepatopancreas and gills of test prawns would not perform their vital functions, which in turn ultimately affect the survival and growth of M. malcolmsonii. The changes noted in protein and histology of test prawns can be taken as biomarkers for monitoring pesticide pollution in aquatic environments. Since this species of prawn is a nutritious delicacy to human being, monitoring aquatic pollution by carbaryl is warranted.

Dietary supplementation of vitamin A, C and E prevents p-dimethylaminoazobenzene induced hepatic DNA damage in rats.

The preventive effect of antioxidant vitamins A, C, E and their analogues against DNA damage induced by a hepatocarcinogen p-dimethylaminoazobenzene (DAB) was assessed by comet assay. For genotoxicity (DNA damage) study, male albino rats were divided into 11 groups, consisting of four rats each. Group I served as control. Group II to VII received 1, 10, 100, 200, 300 and 400 mg per kg body wt of DAB respectively; group VIII to XI received 500 mg/kg body wt of DAB. They were sacrificed by cervical decapitation 3, 6, 12 and 24 h after treatment; livers were excised immediately and subjected to comet assay to measure DNA damage. To study the effect of vitamins, experiments were conducted on a group of 275 rats divided into 3 sets of 25 rats each. First set served as control; second set received 0.06% DAB and third set received 0.06% DAB, along with analogues of vitamins A, C and E. Rats fed with 0.06% DAB were provided water ad libitum for a period of 4 months, followed by a normal (basal) diet for further 2 months. Vitamins A (10,000-50,000 IU), C (75-1000 mg) and E (50-500 mg) and their analogues were given (per kg body wt) to the third set of rats by gavage route once in a week for a period of 6 months. The DAB induced DNA damage only at the highest tested dose of 500 mg/kg body wt. Administration of high doses of vitamin A acid, L-ascorbic acid and vit. E succinate individually prevented the DNA damage. However, administration of a mixture of these vitamins at low doses prevented the DAB-induced DNA damage, which may be due to their synergistic effect. The results indicate that there is a significant advantage in mixed vitamins therapy at low dose over the treatment with individual vitamins.

Comparison of in vitro characteristics of and experimental lesions produced by a clinical and an environmental isolate of Aspergillus flavus.

In the present study, two strains of Aspergillus flavus (one from a human corneal ulcer and one from the environment) were found to be strikingly similar in vitro in terms of thermotolerance, inability to grow in an anaerobic environment and in secreting proteinases; however, one obvious difference was that the clinical isolate produced 120 ppb of aflatoxin B1 in glucose salt medium while the environmental isolate did not produce this toxic metabolite. Alterations in the activities of acid phosphatase (ACP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and glutathione-S-transferase were observed in the liver, kidney and serum in an experimental rat model, irrespective of whether the animal had been challenged with the clinical isolate or the environmental isolate of A. flavus. In rats that had been challenged with the clinical isolate, a significant decrease in the activity of kidney ALP was noted, whereas in rats that had been challenged with the environmental isolate, the reverse was observed. While these differential alterations may have occurred due to differences in the toxin-producing ability of the two isolates, further investigation is warranted to clarify whether other phenotypic, or genotypic, differences are also involved.

Profiles of acid and alkaline phosphatases in the prawn Macrobrachium malcolmsonii exposed to endosulfan.

The present study was performed to determine the toxic effects of endosulfan on the quantitative and qualitative aspects of acid and alkaline phosphatases (ACP and ALP) in Macrobrachium malcolmsonii. Intermoult juvenile prawns were exposed to 32.0 ng/l of endosulfan for a period of 21 days. Samples were taken from the hemolymph, hepatopancreas, gills and muscle of test prawns on the 21st day. The content of ACP and ALP in the hepatopancreas of test prawns were found to be higher in comparison to respective controls. The levels of these enzymes in the hemolymph, gills and muscle of test prawns were found to be lower than in the same tissues of controls. In non-denaturing PAGE, phosphatases appeared as white bands. The intensity of white bands in the hepatopancreas of test prawns were found to be higher when compared to controls. In the hemolymph, gills and muscle of test prawns, the intensity of white bands were found to be lower in comparison to controls. The results of the present study suggest that endosulfan affects the quantity and quality of ACP and ALP in the tissues of M. malcolmsonii.

Carbaryl-induced alterations in biochemical metabolism of the prawn, Macrobrachium malcolmsonii.

The present study was performed to investigate the toxic impact of carbaryl on biochemical metabolism in the hemolymph, brain, hepatopancreas, gills and muscle of intermoult juveniles of the economically important prawn, Macrobrachium malcolmsonii. The concentration of glutathione S-transferase (GST) was found to be higher in test prawns when compared with controls. This suggests that a mechanism of detoxification was in operation to neutralise carbaryl toxicity. However, the toxic effect of carbaryl was not fully neutralised, and hence, alterations were recorded in basic biochemical metabolism of test prawns. The concentration of acetylcholinestrase (AchE) was found to be lower in test prawns than that of controls. Carbaryl toxicity resulted in utilisation of major biochemical constituents, such as total carbohydrate, glycogen, protein and lipid to generate required energy as an attempt to withstand the toxic stress. Glycogenolysis resulted in elevation of total free sugar level in the hemolymph of test prawns. While proteolysis led to elevation of total free amino acid level in test prawns. The content of total lipid have also been found lower in test prawns than that of controls. This suggests that carbaryl toxicity resulted in severe energy crises in test prawns. In the present study, toxic effects of carbaryl impair basic metabolic functions and hence pose a threat to the life of M. malcolmsonii.

Effects of Hg and Cu on hemocytes-mediated functions in the prawn, Macrobrachium malcolmsonii.

Sublethal effects of Hg (9.6, 14.5 and 24.1 microg/l) and Cu (60.5, 90.8 and 150.5 microg/l) on the hemocytes-mediated functions in the juveniles of the economically important freshwater prawns, Macrobrachium malcolmsonii were investigated. The population of total hemocytes, percentile phagocytosis and superoxide anion production were found to be increased in test prawns exposed to the lowest sublethal concentration of these two metals in comparison to controls. This indicates the fact that a mechanism of host-defence was in an active state to encounter metal toxicity. The total hemocytes population, percentile phagocytosis and superoxide anion production were found to be decreased in test prawns exposed to intermediate as well as the highest sublethal concentrations of Hg and Cu when compared with controls. This suggests that high concentrations of both Hg and Cu have inhibitory effects on the immune functions of the hemocytes in the prawn, M. malcolmsonii.

Expression of heat shock protein 70 in freshwater prawn Macrobrachium malcolmsonii (H. Milne Edwards) following exposure to Hg and Cu.

Juveniles of freshwater prawn M. malcolmsonii were exposed to 1/6th concentration of LC50 of Hg and Cu for 48 hr. Sampling was done at 1 8, 12, 16, 24, 30, 36, 42 and 48 hr of exposure. Gill and hepatopancreas were dissected and subjected to one-dimensional electrophoresis. Western blotting was employed to determine the relative concentration of heat shock protein, hsp 70 (stress-70) in each sample. In the gill tissue of the prawn that had been exposed to Hg (0.024 mgHg 1(-1)), stress-70 was detected from the 1st hr till the 16th hr of exposure. But in the gills of Cu exposed prawn, synthesis of stress-70 appeared from the 1st hr till the 24th hr. Synthesis of hsp70 was not recorded after the 24th hr in the gills of exposed prawns. Synthesis of stress-70 was also found to be tissue-specific for both metals in this prawn. When the antibody probe raised against stress-70 was used, synthesis of stress-70 was not observed in hepatopancreas of prawns exposed to Hg or Cu, during the entire period of exposure of 48 hr. The expression of stress-70 in M. malcolmsonii following exposure to Hg and Cu is apparently only transient, and also a differential expression of stress-70 between gill and hepatopancreas was observed for both the metals.