Ocular penetration of levofloxacin, ofloxacin and ciprofloxacin in eyes with functioning filtering blebs: investigator masked, randomised clinical trial.

BACKGROUND/AIMS: To compare the penetration of levofloxacin, ofloxacin and ciprofloxacin in the aqueous humour of eyes with functioning filtering blebs. METHODS: In this investigator-masked study, 48 patients with functioning filtering blebs requiring cataract surgery were randomised into six groups of eight patients. Groups 1, 2 and 3 received topical ofloxacin 0.3% (Ocuflox), ciprofloxacin 0.3% (Ciloxan) and levofloxacin (Quixin) respectively; Groups 4, 5 and 6 received the same treatment with the corresponding oral dose of ofloxacin 400 mg (Floxin), ciprofloxacin 400 mg (Cipro) and levofloxacin 250 mg (Levaquin). Aqueous antibiotic levels were determined by mass spectrometry of aqueous samples from each patient. RESULTS: The mean aqueous level for topical levofloxacin was significantly higher than those achieved by topical ofloxacin or ciprofloxacin (p value = 0.02 and 0.01, respectively). The combination of topical and oral levofloxacin was significantly higher than topical levofloxacin alone (p = 0.05) and the ciprofloxacin combination (p = 0.003) but not significantly higher than the ofloxacin combination therapy. CONCLUSIONS: Topical levofloxacin penetrates better than ofloxacin or ciprofloxacin into the aqueous of eyes with functioning filtering blebs. The combination of topical and oral levofloxacin may be preferable in the treatment of bleb-associated infections (NCT 00392275; Clinical trials.gov).

Patterns of failure in squamous cell carcinoma of the vagina treated with definitive radiotherapy alone: what is the appropriate treatment volume?

The purpose of this study was to review treatment results, sites of failure, and complications in relation to the irradiation volume for carcinoma of the vagina treated with radiotherapy alone. A retrospective review of 65 patients with histologically confirmed squamous cell carcinoma of the vagina who received definitive radiotherapy was undertaken. The 5-year cause-specific survival rates were as follows: Stage I, 91%; Stage IIA (paravaginal extension), 90%; Stage IIB, 55%; Stage III, 89%; and Stage IVA, 62%. The pelvic disease control rates at 5 years were as follows: Stage I, 74%; Stage IIA, 90%; Stage IIB, 79%; Stage III, 89%; and Stage IVA, 67%. Recurrence in the pelvis occurred in 22% of patients. Eighty-five percent of pelvis recurrences were in the primary treatment field. Although pelvic control rates were not increased by use of larger treatment fields (>2,700 cm(3)), moderate acute and late effects were increased with these fields. Carcinoma of the vagina appears to have a different failure pattern than carcinoma of the cervix. The primary failure sites are the vagina and the paracolpal tissues and the inguinal nodes. Because of this, the superior edge of the pelvic fields does not have to extend above the bottom of the sacroiliac joints except with advanced lesions.

Primary ovarian sarcoma: analysis of prognostic variables and the role of surgical cytoreduction.

BACKGROUND: Data regarding the value of cytoreduction and cell histology in ovarian sarcomas are limited. The goal of this study was to assess the value of surgical cytoreduction, preoperative CA 125 levels, stage, histology, and platinum-based chemotherapy in the primary treatment of ovarian sarcomas. METHODS: A retrospective analysis of 47 women with primary ovarian sarcomas was performed. RESULTS: Forty-one patients (87%) presented with advanced stage disease (International Federation of Gynecology and Obstetrics Stage III or IV). Optimal surgical cytoreduction (< 1 cm residual tumor burden) was achieved in 25 patients (53%). Forty patients (85%) had a malignant mixed müllerian tumor whereas 7 patients had a pure sarcoma. Eighteen women with mixed müllerian tumors had homologous tumors and 22 had heterologous elements. Patients treated with platinum-based chemotherapy were significantly more likely to have a response (P = 0.008) compared with those treated with other regimens. Treatment with platinum-based chemotherapy also showed a survival advantage (P = 0.03). Preoperative CA 125 levels were elevated (> 35 U/mL) in 93% of patients with ovarian sarcomas. A preoperative CA 125 level < 75 U/mL was significantly associated with better survival (P = 0.01). In univariate analysis, other significant predictors of improved survival were early stage (P = 0.04), homologous tumors (P < 0.05), and optimal surgical cytoreduction (P < 0.001). In multivariate analysis of various prognostic variables, optimal surgical cytoreduction (P < 0.001) was the most significant factor, followed by histologic subtype (P < 0.02). CONCLUSIONS: Ovarian sarcomas are rare malignancies with a poor prognosis. All women with suspected ovarian carcinoma or sarcoma should have a preoperative CA 125 level taken. Surgical cytoreduction to a residual tumor burden of < or = 1 cm improves outcome and should be the goal of surgery. Although the optimal consolidation chemotherapy regimen remains unknown, platinum should be included as part of the regimen.

Consolidative 32P after second-look laparotomy for ovarian carcinoma.

We report our experience with consolidative 32P after second-look laparotomy. Forty-three patients received consolidative 32P after platinum-based chemotherapy and a negative (39 patients, 91%) or positive (4 patients) second-look laparotomy. Thirty-one patients (72%) initially had stage III (30 patients) or stage IV (1 patient) disease; 28 patients (65%) had grade 3 tumors. Patients had follow-up from 3.5 to 14.9 years (median, 7.7 years); no patient was lost to follow-up. The 5-year rates of control of disease within the abdomen (local control) for the overall group and the subset of patients with stage II-IV disease and a negative second-look laparotomy were 65% and 69%, respectively. The corresponding 5-year survival rates were 78 and 81%, respectively. Multivariate analyses revealed that tumor found at second-look laparotomy significantly influenced the likelihood of local control and cause-specific survival. Acute side effects included cellulitis (1 patient) and ileus (3 patients). Two patients (5%) experienced severe late complications; both experienced small bowel obstruction that necessitated surgical intervention. Consolidative 32P appears to reduce the risk of recurrence and improve survival after negative second-look laparotomy. The risk of significant complications is low.

Adjuvant 32P in the treatment of ovarian carcinoma.

The purpose of this study was to evaluate the efficacy of adjuvant 32P for patients with high-risk, early-stage ovarian carcinoma. Twenty-five patients underwent apparent complete resection followed by 32P (15 mCi) at the University of Florida between 1976 and 1993. Minimum and median follow-up times were 3 and 8 years, respectively. The rate of local control at 10 years was 83%. Four of the 5 patients who experienced recurrent disease had a component of intra-abdominal disease at the time of relapse. The absolute and cause-specific survival rates at 10 years were 68% and 82%, respectively. There were no severe acute complications. Five patients experienced significant late complications, including chronic abdominal cramping that was treated conservatively (3 patients) and small bowel obstruction necessitating surgical intervention (2 patients). Adjuvant 32P results in disease control and survival rates that are similar to those observed after adjuvant chemotherapy. However, the risk of late complications, particularly small bowel obstruction, is higher.

Anaphylaxis to carboplatin following multiple previous uncomplicated courses.

Hypersensitivity reactions to carboplatin are rare but potentially life-threatening complications. A patient with an anaphylactic reaction to carboplatin is presented. This patient had received multiple courses of platinum-based chemotherapy including cisplatin and carboplatin. Close patient monitoring during chemotherapy is essential and skin testing to identify the etiologic agent is indicated when hypersensitivity reactions occur in the setting of combination chemotherapy.

Radiotherapy alone for carcinoma of the vagina: the importance of overall treatment time.

PURPOSE: Review treatment results, complications, and the importance of overall treatment time for carcinoma of the vagina treated with radiotherapy alone. METHODS AND MATERIALS: Between October 1964 and October 1990, 65 patients with histologically confirmed carcinoma of the vagina received definitive radiotherapy at the University of Florida. All patients had a minimum 2-year follow-up. Most patients were treated with a combination of external-beam radiotherapy and brachytherapy. The probability of pelvic control, cause-specific survival, and complications was calculated and multivariate analyses were performed. The log-rank test was used to determine significance levels between the curves. RESULTS: The 5-year cause-specific survival rates were, Stage 0 (six patients), 100%; Stage I (17 patients), 94%; Stage IIA (six patients), 80%; Stage IIB (ten patients), 39%; Stage III (twn patients), 79%; and Stage IVA (six patients), 62%. The pelvic control rates at 5 years were: Stage 0, 100%; Stage I, 87%; Stage IIA, 88%; Stage IIB, 68%; Stage III, 80%; and Stage IVA, 67%. The parameters of stage, patient age, total dose to primary site, and overall treatment time were evaluated in a multivariate analysis. The single most important predictor of pelvic control was overall treatment time. If the entire course of radiotherapy (external beam + implant) was completed within 9 weeks (63 days), the pelvic control rate was 97%. The pelvic control rate was only 54% if treatment time extended beyond 9 weeks (p = .0003). The rate of severe complications was 12%, and the incidence increased with increasing total primary dose. CONCLUSION: Radiotherapy alone can cure a significant proportion of patients with carcinoma of the vagina. Treatment should be completed without significant interruption, preferably within 9 weeks.

Stage III ovarian carcinoma: an analysis of treatment results and complications following hyperfractionated abdominopelvic irradiation for salvage.

PURPOSE: Patients with persistent disease found at laparotomy following platinum-based chemotherapy for Stage III ovarian carcinoma have a remote chance of cure with second-line chemotherapy or conventional radiotherapy. To decrease relapse rates and improve tolerance, we have used twice-daily radiotherapy in 28 such patients. METHODS AND MATERIALS: Twenty-eight patients with Stage III epithelial ovarian carcinoma were treated with curative intent at the University of Florida with hyperfractionated, continuous-course radiotherapy for persistent disease at laparotomy after administration of platinum-based chemotherapy. All patients received .8 Gy per fraction, twice daily, to a mean total dose of 30.2 Gy to the whole abdomen and pelvis; 20 patients had additional radiotherapy to the pelvis (mean, 14.54 Gy). All patients had undergone two to four (mean, 2.6) laparotomies for ovarian carcinoma and had received 6-28 (mean, 12) cycles of chemotherapy before irradiation. RESULTS: With a 2-year minimum follow-up, survival rates at 1, 2, and 5 years were as follows: absolute survival, 79%, 50%, 21%; relapse-free survival, 52%, 36%, 19%. For the 11 patients with no evidence of gross residual disease after the second-look laparotomy, the absolute survival rates were 100%, 73%, and 27%. This was superior to the rates of 65%, 34%, and 18% for the 17 patients who had gross residual disease. Only two patients required treatment breaks. Four patients required surgical intervention for small-bowel obstruction, which in two cases revealed recurrent disease. Two patients died of treatment-related complications. Twenty-two of 23 failures occurred in the abdomen and/or pelvis. CONCLUSION: Although most patients eventually relapse, a small percentage have had a prolonged disease-free interval. Since treatment was relatively well tolerated, escalation of the dose of hyperfractionated abdominopelvic irradiation is being investigated.

Renal disease associated with circulating antineutrophil cytoplasm activity.

We report our detailed observations on a group of 30 consecutive patients with renal disease, histologically demonstrated glomerulitis or necrotizing vasculitis, and circulating antineutrophil cytoplasm activity (ANCA). The annual incidence of ANCA-related renal disease was seven cases per million population. The sensitivity of serum ANCA for histologically proved glomerular vasculitis was 79 per cent, with a specificity of 87 per cent. Most patients responded to treatment with cyclophosphamide and steroids but complications of therapy occurred in just over half the patients and were serious in 20 per cent. Actuarial survival at 1 year was 60 per cent. Age and dialysis requirement did not influence outcome and the only identified adverse prognostic factor was hypoxic lung disease. We conclude that the association of ANCA with renal disease is not rare and that positive serology accurately identifies a homogeneous group of patients with similar clinical, histological, and prognostic features. Separation of these patients into those with the disease entities of Wegener's granulomatosis and microscopic polyarteritis is not straightforward on clinical and histological criteria, and such a distinction does not yield useful therapeutic or prognostic information. Simple urinalysis should always be carried out in patients with undiagnosed systemic illness in order to identify renal disease. ANCA-related renal disease can be treated successfully with cyclophosphamide and steroids and elderly patients should not be excluded from treatment, including dialysis if necessary. The ANCA test is simple and quick to perform and, in the appropriate clinical setting, accurately identifies patients who may benefit from immunosuppressive treatment before a histological diagnosis can be established.

Stage IB or IIA-B carcinoma of the intact uterine cervix greater than or equal to 6 cm in diameter: is adjuvant extrafascial hysterectomy beneficial?

This is an analysis of 150 patients with Stage IB or IIA-B carcinoma of the intact uterine cervix greater than or equal to 6 cm in diameter treated with irradiation alone (75 patients) or irradiation followed by surgery (75 patients) at the University of Florida between October 1964 and June 1983. Minimum follow-up in this series was 5 years. There was no significant difference in the distribution of prognostic factors between the two treatment groups. The 5-year local control rate was 74% with irradiation alone and 76% with irradiation and surgery. The 5-year survival rates for irradiation alone versus irradiation plus surgery were as follows: cause specific, 62% and 55%, and absolute, 54% and 52%. The proportion of patients who developed treatment complications necessitating hospitalization or a second operation was 4/75 (5%) after irradiation alone and 12/75 (16%) after irradiation and surgery. The authors conclude that the routine use of adjuvant extrafascial hysterectomy is not warranted in this patient population.

Hormonally active gynecologic tumors.

Hormonally active gynecologic tumors include gestational trophoblastic disease (GTD) and some of the primary ovarian tumors. The presenting symptoms in patients with these tumors are frequently related to their endocrine activity. The main hormone produced by gestational trophoblastic disease is human chorionic gonadotropin (HCG) and the main symptoms are those associated with a normal pregnancy, except they are frequently exaggerated. The endocrinally active ovarian tumors are mainly those of the sex-cord stromal group and these may produce any of the sex steroids (estrogens, androgens, or progestins). Some germ cell tumors of the ovary are hormonally active because they contain syncytio-trophoblastic cells which produce HCG. There are two specialized types of mature teratomas that are discussed: struma ovarii, which produce thyroid hormones, and carcinoids, which produce serotonin.

Clinical stage I and II endometrial carcinoma treated with surgery and/or radiation therapy: analysis of prognostic and treatment-related factors.

This is an analysis of 266 patients with clinical stage I and II endometrial carcinoma treated with curative intent at the University of Florida between October 1964 and December 1980. There was a minimum 5-year follow-up. Thirty-nine patients who died of intercurrent disease less than 5 years from treatment were excluded from analysis of pelvic disease control and determinate disease-free survival. All patients were included in the analysis of complications. Pelvic disease control and determinate disease-free survival rates at 5 years were 91 and 88%, respectively, for stage I and 84 and 68% for stage II. There was no apparent difference in the rates of local control and survival or in the incidence of complications when comparing preoperative with postoperative radiation therapy. Tumor grade, stage, depth of myometrial invasion, and history of exogenous estrogen use or abnormal estrogen balance were of prognostic significance. Data on pelvic disease control, survival, and treatment complications are outlined, and management guidelines are discussed.

Carcinoma of the intact uterine cervix, stage IB-IIA-B, greater than or equal to 6 cm in diameter: irradiation alone vs preoperative irradiation and surgery.

This is an analysis of 123 patients with Stage IB-IIA-B carcinoma of the intact uterine cervix, 6 cm or greater in diameter, who were treated with curative intent at the University of Florida with radiation alone or radiation followed by a hysterectomy between October 1964 and February 1982. There is a minimum follow-up of 2 years in all patients; 87% of all recurrences and 91% of pelvic recurrences occurred within this time period. Examination of pelvic control rates, as well as disease-free survival, showed no significant advantage in pelvic control, disease-free survival, or absolute survival for either treatment group when compared by stage and tumor size. The incidence of severe complications was 6% for patients treated with irradiation alone and 15% for those treated with irradiation and surgery (p = 0.119).

MR imaging of uterine leiomyomas and their complications.

Magnetic resonance (MR) imaging in eight patients with uterine leiomyomas and in eight normal female volunteers clearly depicted the size, shape, and position of the corpus uteri and demonstrated adjacent anatomic structures to good advantage in transaxial, coronal, and sagittal planes. Spin echo (SE) with short repetition time (TR) and short echo time (TE) values was judged best for overall delineation of anatomic structures. Longer TR and TE times were used to differentiate myometrium from endometrium. Detection and characterization of complications of uterine myomas were facilitated by the use of multislice/multiecho SE techniques, but in general TE values greater than 60 ms were not needed to differentiate endometrium from myometrium and in most cases did not improve the MR depiction of abnormalities. Calculated T1 and T2 relaxation times from this preliminary study do not demonstrate a clear advantage in further characterizing uterine abnormalities.

Perioperative changes in blood pressure and heart rate.

In order to evaluate the possible physiologic significance of intra- and postoperative hypotension, we monitored arterial blood pressure and heart rate continuously for 36 hr starting the night before and ending the morning after operation in 34 gynecologic patients. The lowest pressures that occurred during physiologic sleep were compared with the lowest arterial pressures that occurred during anesthesia without deliberate hypotension. Two values were calculated: a preoperative baseline pressure, i.e., the average value recorded during the second hour of monitoring on the night before surgery, and a preanesthetic standard pressure, i.e., the average value of 15 consecutive measurements made at 1-min intervals in the operating room before the induction of anesthesia. The results indicate that a systolic pressure 10% below the PAS during anesthesia does not constitute physiologically significant hypotension because this range resembles the range that occurs spontaneously during unmedicated sleep or sleep aided with a mild hypnotic. These physiologic nadirs in blood pressure are assumed to be tolerated well by the patient. Intraoperative pressures in elderly patients frequently drifted below sleep-associated levels of blood pressure and may, therefore, constitute physiologically significant hypotension.

Association of Fanconi's anemia and squamous-cell carcinoma of the lower female genital tract with condyloma acuminatum. A report of two cases.

Two young women had Fanconi's anemia and genital human papillomavirus infection associated with multicentric genital neoplasia. One of these women represented the first documented case of death from vaginal squamous carcinoma associated with Fanconi's anemia. In these two women an apparent biologic compression of the natural history of vulvar and vaginal carcinoma was observed. The finding of condyloma acuminatum in both of them prior to the onset of carcinoma suggests a partial causal association. Involvement of the cervix, vagina, vulva and perianal epithelium by the oncogenic process implies that a field effect occurred in those areas.

Prognostic and treatment factors affecting pelvic control of Stage IB and IIA-B carcinoma of the intact uterine cervix treated with radiation therapy alone.

This is a retrospective analysis of 264 patients with Stage IB and IIA-B carcinoma of the cervix treated with curative intent at the University of Florida from October 1964 through April 1980. There is a minimum 2-year follow-up. Patients dead of distant metastases (13), dead from intercurrent disease (14), or lost to follow-up (1) less than 24 months from treatment with pelvic disease controlled were excluded from analysis of pelvic control. All patients were included in analysis of complications and survival. Tumor size and hematocrit were noted to be significant prognostic factors with regard to control of disease in the pelvis in Stage IB and IIA cancers. Tumor size and hematocrit also influenced pelvic control in Stage IIB, but to a lesser extent than in Stages IB and IIA. Patient age was a weak prognostic factor for control of disease in the pelvis for Stages IB, IIA, and IIB, but more strongly influenced pelvic control when considered in conjunction with tumor size and hematocrit. Overall treatment time influenced pelvic control in all cases when the size of the lesion was greater than or equal to 6 cm. In lesions greater than or equal to 6 cm in diameter, the amount of tumor regression noted at the time of the radium application after 3500 to 4000 rad external beam irradiation was a predictor of pelvic control. Data on treatment complications and survival are included, and future treatment strategies discussed.

Computed tomography of uterine papillary serous carcinoma.

We describe the CT appearances of a fairly commonly encountered "special variant" carcinoma of the uterine corpus called uterine papillary serous carcinoma ( UPSC ). UPSC closely resembles ovarian papillary serous carcinoma microscopically but CT with contrast can differentiate between these two entities. In addition CT in this patient clearly showed the characteristic spread mode of this particularly aggressive form of endometrial carcinoma. Because UPSC has a significantly higher relapse rate than other histologic types of endometrial carcinoma it is important to recognize it at the time of the CT staging procedure. The spread pattern of UPSC suggests the need for adjuvant irradiation or chemotherapy.

Cardiopulmonary effects of acute thallium poisoning.

Gastrointestinal distress and alopecia are the most commonly reported symptoms of acute thallium intoxication; however, cardiac and pulmonary disease may dominate the acute stages of the disease. We report four cases which illustrate the importance of cardiac and respiratory disease in this syndrome.