Long-term remission of clear cell carcinoma of the cervix after chemoradiation with 109 cycles of paclitaxel: a case report and literature review.

BACKGROUND: Clear cell carcinoma of cervix (CCCC) is a rare cervical neoplasm that is usually associated with diethylstilbestrol (DES) exposure in utero as a primary risk factor. Advanced stage disease typically has poor outcomes and no evidence-based approach exists to guide clinicians in treating this rare disease. CASE: The authors report a case of locally advanced CCCC in a 37-year-old Caucasian female. She underwent chemoradiation therapy that included 109 courses of paclitaxel chemotherapy until no disease could be detected on imaging studies. She is now disease-free 13 years after discontinuing chemotherapy. CONCLUSION: A prolonged course of single agent paclitaxel after completing standard radiation therapy was successful in achieving remission in a patient with this rare disease.

Systemic toxoplasmosis in captive flying-foxes.

Systemic toxoplasmosis caused by Toxoplasma gondii was diagnosed in two juvenile, captive flying-foxes (Pteropus conspicillatus and P. scapulatus), which died following respiratory distress. One animal displayed clinical signs suggestive of neurological disease. This is the first report of this disease in megachiropteran bats and adds to the list of differential diagnoses for both systemic and neurological disease in these animals. The role of captivity in the exposure and development of the disease is discussed.

Efficacy and safety of erlotinib HCl, an epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor, in patients with advanced ovarian carcinoma: results from a phase II multicenter study.

The aim of this single-arm, phase II study was to estimate the tumor response rate and safety profile of erlotinib HCl (erlotinib, Tarceva, OSI-774) monotherapy in patients with refractory, recurrent, HER1/EGFR-positive epithelial ovarian tumors, who had failed prior taxane and/or platinum-based chemotherapy. Thirty-four patients received 150 mg erlotinib orally once daily for up to 48 weeks or until disease progression or dose-limiting toxicity. Two patients had partial responses, lasting 8+ and 17 weeks, giving an objective response rate of 6% (95% confidence interval [CI], 0.7-19.7%). Fifteen patients (44%) had stable disease, and 17 patients (50%) had progressive disease. Median overall survival was 8 months (95% CI, 5.7-12.7 months), with a 1-year survival rate of 35.3% (95% CI, 19.8-53.5%). Patients with rash survived significantly longer than those without (P= 0.009), correlating with rash grade. Erlotinib was generally well tolerated. The most frequent erlotinib-related adverse events were rash (68%) and diarrhea (38%). Erlotinib had marginal activity but was generally well tolerated. The safety profile appears more favorable than typically experienced with standard chemotherapeutic agents, which is encouraging in these heavily pretreated patients. Combination of erlotinib with chemotherapy or other targeted agents should be considered.

Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan.

PURPOSE: To compare the efficacy and safety of pegylated liposomal doxorubicin (PLD) and topotecan in patients with epithelial ovarian carcinoma that recurred after or didn't respond to first-line, platinum-based chemotherapy. PATIENTS AND METHODS: Patients with measurable and assessable disease were randomized to receive either PLD 50 mg/m(2) as a 1-hour infusion every 4 weeks or topotecan 1.5 mg/m(2)/d for 5 consecutive days every 3 weeks. Patients were stratified prospectively for platinum sensitivity and for the presence or absence of bulky disease. RESULTS: A total of 474 patients were treated (239 PLD and 235 topotecan). They comprised the intent-to-treat population. The overall progression-free survival rates were similar between the two arms (P =.095). The overall response rates for PLD and topotecan were 19.7% and 17.0%, respectively (P =.390). Median overall survival times were 60 weeks for PLD and 56.7 weeks for topotecan. Data analyzed in platinum-sensitive patients demonstrated a statistically significant benefit from PLD for progression-free survival (P =.037), with medians of 28.9 for PLD versus 23.3 weeks for topotecan. For overall survival, PLD was significantly superior to topotecan (P =.008), with a median of 108 weeks versus 71.1 weeks. The platinum-refractory subgroup demonstrated a nonstatistically significant survival trend in favor of topotecan (P =.455). Severe hematologic toxicity was more common with topotecan and was more likely to be associated with dosage modification, or growth factor or blood product utilization. CONCLUSION: The comparable efficacy, favorable safety profile, and convenient dosing support the role of PLD as a valuable treatment option in this patient population.

Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer.

PURPOSE: Stealth liposomal doxorubicin (Alzal Corp, Palo Alto, CA) has a slower clearance rate than free doxorubicin, resulting in sustained serum levels. Liposomal encapsulation also leads to increased concentration of drug in tumor tissue. Meta-analysis of previous studies has shown that doxorubicin has activity in epithelial ovarian cancer. The current study was developed to examine the activity of Stealth liposomal doxorubicin in platinum- and paclitaxel-refractory ovarian cancer. PATIENTS AND METHODS: Patients had epithelial ovarian cancer that either progressed on or recurred within 6 months of completion of platinum and paclitaxel chemotherapy. All patients had measurable disease. Stealth liposomal doxorubicin was administered at 50 mg/m(2) every 4 weeks as a 1-hour infusion. RESULTS: Eighty-nine patients were treated and included in an intent-to-treat analysis. There were 82 patients who were platinum and paclitaxel refractory and met all study criteria. There was one complete response and 14 partial responses, for a total response rate of 16.9% (95% confidence interval [CI], 9.1% to 24.6%). For platinum- and paclitaxel-refractory patients, the response rate was 18.3% (95% CI, 9.9% to 26.7%). Median time to progression was 19. 3 weeks for the entire population. Ten patients (11.2%) withdrew because of adverse events related to the drug (palmar-plantar erythrodysesthesia [PPE], n = 3; asthenia, n = 2; cardiac, n = 2; neutropenia, n = 1; stomatitis, n = 1; and edema, n = 1). There were no drug-related fatal events. There were only eight grade 4 adverse events attributable to the drug. Stomatitis, PPE, and skin lesions were managed with dose reductions and delays in most cases. CONCLUSION: Stealth liposomal doxorubicin has activity in refractory epithelial ovarian cancer. PPE and stomatitis can usually be managed by dose adjustment. The ease of administration makes this an attractive agent.

A phase I/II dose escalation study of carboplatin in the treatment of newly diagnosed patients with advanced ovarian cancer receiving paclitaxel.

The objective of this study was to determine the maximum tolerated dose of carboplatin when administered with paclitaxel in previously untreated patients with ovarian cancer. Patients were treated with paclitaxel at 225 mg/m2 for 3 hours followed by carboplatin at an area under the curve (AUC) of 6, 7, 8, or 9 every 3 weeks. Granulocyte colony-stimulating factor was added if needed to maintain dose intensity before dose reductions were used for grade 4 hematologic toxicity or febrile neutropenia. Twenty-two patients were enrolled in the study. At the AUC 6 level, five of six patients finished all six cycles. At the AUC 7 level, four of five patients completed six cycles, although three required dose reductions for toxicity. At the AUC 8 level, all four patients completed six cycles and two required dose reductions. The AUC 9 level was not well tolerated. Only four of seven patients completed six cycles. Neutropenia was common, and transient thrombocytopenia was more severe and required dose reduction, especially in later cycles. An AUC of 8 is the maximum tolerated dose of carboplatin in combination with paclitaxel at 225 mg/m2 for 3 hours.

Hapalotrema (Digenea: Spirorchidae) in the green turtle (Chelonia mydas) in Australia.

Hapalotrema mehrai Rao, 1976 and Hapalotrema postorchis Rao, 1976 (Digenea: Spirorchidae) are redescribed from the heart and pulmonary arteries of the green turtle, Chelonia mydas, from Moreton Bay in south-eastern Queensland. Hapalotrema pambanensis Gupta and Mehrotra, 1981 from C. mydas in India is made a synonym of H. mehrai. Hapalotrema dorsopora Dailey, Fast and Balazs, 1993 from C. mydas from Hawaii was described with a dorsally opening uterine pore, but this is found to be the opening of Laurer's canal; therefore H. dorsopora is also made a synonym of H. mehrai. In addition to differences in the numbers of testes and general dimensions, H. mehrai and H. postorchis differ in the development of Laurer's canal and in the absence of a canalicular seminal receptacle in H. postorchis.

Lesions caused by cardiovascular flukes (Digenea: Spirorchidae) in stranded green turtles (Chelonia mydas).

Evidence of infection with spirorchid flukes (Digenea: Spirorchidae) was sought at necropsy of 96 stranded green turtles, Chelonia mydas, that were examined during the course of a survey of marine turtle mortality in southeastern Queensland, Australia. Three species of spirorchid (Hapalotrema mehrai, H. postorchis, and Neospirorchis schistosomatoides) were identified. Severe disease due to spirorchid fluke infection (spirorchidiasis) was implicated as the principal cause of mortality in 10 turtles (10%), and appeared to be one of multiple severe problems in an additional 29 turtles (30%). Although flukes were observed in only 45% of stranded C. mydas in this study, presumed spirorchid fluke infection was diagnosed in an additional 53% of turtles, based principally on characteristic necropsy lesions and to a lesser extent on the histopathological detection of spirorchid eggs. Characteristic necropsy lesions included miliary spirorchid egg granulomas, which were observed most readily on serosal surfaces, particularly of the small intestine. Cardiovascular lesions included mural endocarditis, arteritis, and thrombosis, frequently accompanied by aneurysm formation. Resolution of thrombi was observed to occur via a combination of granuloma formation about indigestible components (spirorchid fluke egg shells) and exteriorization through the vessel wall, which resulted in granulomatous nodules on the adventitial surface. Septic aortic thrombosis complicated by disseminated bacterial infection, observed in five turtles, was recorded for the first time. Egg granulomas were ubiquitous in turtle tissues throughout this study. Although they generally appeared to be mild or incidental lesions, they were occasionally associated with severe multifocal granulomatous pneumonia or meningitis.

An outbreak of malignant catarrhal fever in young rusa deer (Cervus timorensis).

On the basis of clinical signs and histological findings eight 9-month-old male rusa deer (Cervus timorensis) were diagnosed with sheep associated-malignant catarrhal fever. Following a variable course involving rectal temperatures around 40.5 degrees C, depression, inappetence, diarrhoea, corneal opacity and hypopyon all animals died or were euthanased over a 5-week period. Severe multifocal vasculitis, mainly periglomerular and in the arcuate vessels were consistent histological findings which in the past have been adequate to confirm clinical diagnosis of sheep associated-malignant catarrhal fever. A nested polymerase chain reaction test has been used to detect a sheep associated-malignant catarrhal fever PRC product, 238 base-pairs in size, in DNA extracted from lymphocyte preparations. The result supported the diagnosis of sheep associated-malignant catarrhal fever in these deer.

Phase I dose escalation of paclitaxel in patients with advanced ovarian cancer receiving cisplatin: rapid development of neurotoxicity is dose-limiting.

PURPOSE: To determine the maximum-tolerable dose (MTD) of paclitaxel in a phase I dose-escalation study when combined with cisplatin in patients with advanced ovarian cancer receiving filgrastim for prophylaxis of myelosuppression. PATIENTS AND METHODS: A total of 23 patients with stage II (bulky residual), III, or IV epithelial ovarian cancer were treated (following debulking surgery) with paclitaxel as a 3-hour infusion followed by cisplatin (75 mg/m2) administered over 4 hours on day 1, repeated every 21 days for six cycles. Filgrastim (5 micrograms/kg/d) was administered subcutaneously (SC) beginning on day 2 of each cycle through neutrophil recovery (absolute neutrophil count [ANC] > 10,000/microL). Patients were assigned to one of six escalating dose levels of paclitaxel: 150 (n = 3), 175 (n = 3), 200 (n = 3), 225 (n = 4), 250 (n = 4), and 275 mg/m2 (n = 6). RESULTS: At each paclitaxel dose level (150, 175, 200, 225, 250, and 275 mg/m2), the numbers of patients who completed six cycles without dose reduction were three (100%), three (100%), two (66%), two (50%), three (75%), and zero (0%), respectively. The numbers of patients who experienced a grade III/IV adverse event (hematologic or nonhematologic) were zero (0%), two (66%), two (66%), one (25%), four (100%), and five (80%), respectively. Reasons for dose reduction included neurotoxicity (225 mg/m2, n = 1; 275 mg/m2, n = 2), neutropenia (225 mg/m2, n = 2), diarrhea (275 mg/m2, n = 2), and nephrotoxicity (225 mg/m2, n = 1). Reasons for not completing six cycles at full or reduced dose included neuropathy (200, 225, and 275 mg/m2, n = 1 each) physician request (275 mg/m2, n = 1), and death (275 mg/m2, n = 1). Hematopoietic toxicity was minimal. Six patients developed grade III/IV neutropenia. No patient developed thrombocytopenia below a level of 50,000/microL. CONCLUSION: The MTD of paclitaxel was determined to be 225 mg/m2 when administered as a 3-hour infusion and combined with cisplatin (75 mg/m2). Nonhematologic dose-limiting toxicities were neuropathy and diarrhea. The neuropathy often had a rapid onset, especially at the higher dose levels.

Epizootic mortality of free-living green turtles, Chelonia mydas, due to coccidiosis.

At least 70 wild green sea turtles, Chelonia mydas, died in the Moreton Bay area of southeast Queensland, Australia over 6 wk in spring 1991. Based on the necropsy of 24 turtles, there was a severe enteritis or encephalitis associated with Caryospora cheloniae, a coccidial pathogen previously recorded only in farm-reared Ch. mydas hatchlings. Infection was characterized by the presence of coccidia in extra-intestinal lesions. Oocysts were observed to sporulate, after which sporozoites escaped into seawater to form a novel stellate configuration. We conclude that C. cheloniae is pathogenic for life stages other than hatchling Ch. mydas and that naturally-occurring coccidiosis is a significant disease of free-living Ch. mydas.

Suicide by poisoning.

An epidemiological evaluation was conducted on 270 patients who died at the General Hospital, Port-of-Spain after presenting with deliberate self-poisoning between January, 1986 and June, 1990. The cause of death was confirmed by autopsy and toxicological analysis. Epidemiological variables of age, sex, race, precipitating factors and types of poison used were assessed. It was found that the male to female ratio was 2.7:1. East Indians accounted for 54.4%, Africans 42.0%, people of mixed ethnic origin 3% and Caucasians 0.6%. The majority of cases (52.6%) were seen in the age group 11-34 years. "Lovers' quarrels" (35.4% of cases), psychiatric illness (27.8% of cases) and family disputes (27% of cases) were reported as the most frequent precipitating events in suicide. East Indians predominated in those suicides precipitated by "lovers' quarrels" and family disputes, accounting for 63.2% and 58.9% of these cases, respectively; while for those suicides in which psychiatric illnesses were the main precipitating event. Africans were represented by 53.3% and East Indians 45.3%. Depression was the most common psychiatric illness diagnosed. Paraquat was the most popular poison used in 63.7% of the suicidal cases, and other agrochemicals were used in 20% of cases.

Suicide by poisoning

An epidemiological evaluation was conducted on 270 patients who died at the General Hospital, Port-of-Spain after presenting with deliberate self-poisoning between January, 1986 and June, 1990. The cause of death was confirmed by autopsy and toxicological analysis. Epidemiological variables of age, sex, race, precipitating factors and types of poison used were assessed. It was found that the male to female ratio was 2.7:1. East Indians accounted for 54.4percent , Africans 42.0 percent, people of mixed ethnic origin 3 percent and Caucasians 0.6 percent. The majority of cases (52.6 percent) were seen in the age group 11-34 years. "Lovers' quarrels" (35.4 percent of cases), psychiatric illness (27.8 percent of cases) and family disputes (27 percent of cases) were reported as the most frequent precipitating events in suicide. East Indians predominated in those suicides precipitated by "lovers' quarrels" and family disputes, accounting for 63.2 percent and 58.9 percent of these cases, respectively; while for those suicides in which psychiatric illnesses were the main precipitating event, Africans were represented by 53.3 percent and East Indians 45.3 percent. Depression was the most common psychiatric illness diagnosed. Paraquat was the most popular poison used in 63.7 percent of the suicidal cases, and other agrochemicals were used in 20 percent of the cases. (AU)

Suicide by poisoning

An epidemiological evaluation was conducted on 270 patients who died at the General Hospital, Port-of-Spain after presenting with deliberate self-poisoning between January, 1986 and June, 1990. The cause of death was confirmed by autopsy and toxicological analysis. Epidemiological variables of age, sex, race, precipitating factors and types of poison used were assessed. It was found that the male to female ratio was 2.7:1. East Indians accounted for 54.4%, Africans 42.0%, people of mixed ethnic origin 3% and Caucasians 0.6%. The majority of cases (52.6%) were seen in the age group 11-34 years. "Lovers' quarrels" (35.4% of cases), psychiatric illness (27.8% of cases) and family disputes (27% of cases) were reported as the most frequent precipitating events in suicide. East Indians predominated in those suicides precipitated by "lovers' quarrels" and family disputes, accounting for 63.2% and 58.9% of these cases, respectively; while for those suicides in which psychiatric illnesses were the main precipitating event, Africans were represented by 53.3% and East Indians 45.3%. Depression was the most common psychiatric illness diagnosed. Paraquat was the most popular poison used in 63.7% of the suicidal cases, and other agrochemicals were used in 20% of the cases.

Depth of myometrial invasion in endometrial cancer: preoperative assessment by transvaginal ultrasonography.

Twenty-five patients with cancer of the uterus underwent transvaginal sonography (TVS) to assess depth of myometrial invasion. All scans were performed with a 5.0-MHz curvilinear array probe (Toshiba, Inc., Tustin, CA) within 1 week of hysterectomy. In 21 cases (84%) sonography correctly predicted the depth of invasion (within 15% of actual). Only one of three cases with cervical involvement was detected. Transvaginal sonography can accurately detect depth of myometrial invasion and is well suited as a screening test to detect high-risk patients for consultation or referral.

Transvaginal sonography of postmenopausal ovaries with pathologic correlation.

The sonographic appearance of 67 ovaries in 34 postmenopausal women who underwent preoperative transvaginal sonography (TVS) was correlated to findings on pathologic examination. Both ovaries were detected by TVS in 60% of the women examined; in 85%, at least one ovary was detected. The size of the normal, sonographically visualized postmenopausal ovary was 2.2 +/- 0.7 cm in transverse, 1.2 +/- 0.3 cm in anteroposterior, and 1.1 +/- 0.6 cm in longitudinal axes, with an average volume of 2.6 +/- 2.0 cm3. The average size of ovaries that were not detected by TVS was 0.7 x 0.4 cm (range, 0.3 to 1.3 cm); most of these (five of six) were atrophic on pathologic exam. The difference between actual and sonographically measured size was negligible (TVS overestimated by 0.3 cm). Four simple cysts that ranged from 0.5 to 3.5 cm were found by TVS and confirmed pathologically, as were three benign serous cystadenomas that ranged from 2.5 to 3.5 cm, one 3 x 6-cm tubal carcinoma, and one 1 X 4-cm paratubal cyst. TVS missed a 6-cm dermoid, a 2.5-cm cystadenoma, a 0.8-cm Sertoli cell tumor, and a 0.5-cm fibrothecoma that were nonpalpable but that were found on pathologic examination. None of the missed lesions were palpable preoperatively. The positive predictive value was 94% for detection of an ovarian mass; the negative predictive value for exclusion of an ovarian lesion was 92%. It is concluded that TVS can accurately delineate the ovaries in most, but not all, postmenopausal women and that only rarely will pathologic lesions not be detected by TVS.

Adjuvant chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (PAC) for early-stage high-risk endometrial cancer: a preliminary analysis.

Between October 1985 and January 1989, 33 patients with stage I (31) or clinically occult stage II (2) endometrial cancer at a high risk for recurrence were entered in a prospective study evaluating adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy. Eligibility criteria included grade 2 tumors with middle- or outer-third myometrial invasion (16), grade 3 tumors with any degree of myometrial invasion (17), presence of extrauterine disease with no gross residual (17), or a high-risk histologic subtype including papillary serous (4), adenosquamous (5), or clear cell (1) tumors. Patients received PAC (50/50/500 mg/m2) at 4-week intervals for six cycles. Thirty patients (90%) completed therapy. Toxicity included severe neutropenia in 14 patients, neutropenic sepsis in 2 patients, and doxorubicin-related cardiomyopathy in 1 patient. There were no treatment deaths. Current median follow-up is 25 months. Nine patients (27%) have developed a recurrence, 7 of whom died, after a median interval of 14 months. Eight of the 9 with recurrence initially had extrauterine disease (P = 0.02). The resulting 2-year actuarial progression-free and overall survival rates were 79 and 83%, respectively. The median progression-free interval was 29 months for patients with extrauterine disease and 45+ months for those with no extrauterine disease (P = 0.02). These results suggest that a phase 3 randomized trial comparing adjuvant PAC with radiation therapy is warranted.

Self-instruction to prevent HIV infection among African-American and Hispanic-American adolescents.

This study tested the efficacy of self-instruction intervention to reduce avoidable risks for HIV infection associated with drug use and unsafe sexual activity among African-American and Hispanic adolescents (N = 60). After completing pretests, adolescent participants in the study were randomly divided into three conditions. Participants in one condition received a self-instructional guide about AIDS and its transmission along with group instruction in using the guide. Adolescents in another condition received the guide without group instruction. Participants in the third condition received neither the guide nor group instruction. Outcome findings indicate that participants in the two self-instruction conditions improved more between pretest and posttest assessments on measures of HIV infection risk compared with adolescents in the control condition.