Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes.

BACKGROUND: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer. PATIENTS AND METHODS: Patients had a maximum of three prior chemotherapy lines with no more than two prior platinum-containing regimens and a progression-free interval after the last dose of platinum <12 months. A total dose of 4 mg/m(2)/cycle (0.8 mg/m(2)/day from day 1 to day 5) was administered, repeated every 28 days. RESULTS: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less. CONCLUSION: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity.

The prognostic relevance of histological type in uterine sarcomas: a Cooperation Task Force (CTF) multivariate analysis of 249 cases.

PURPOSE OF INVESTIGATION: The objective of this retrospective multicenter study was to assess the prognostic relevance of histologic type in uterine sarcomas. METHODS: The hospital reports of 249 patients with uterine sarcomas were reviewed. Surgery was the initial therapy for all patients. Histologic type was leiomyosarcoma in 95 cases, low-grade endometrial stromal sarcoma (ESS) in 19, high-grade ESS in 34, and carcinosarcoma in 101. Postoperative treatment was given without well-defined protocols. Median follow-up of survivors was 97 months. RESULTS: In the whole series 2-year, 5-year, and 10-year survival rates were 53.5%, 41.6%, and 35.8%, respectively, and median survival was 31 months. At univariate analysis survival was significantly related to stage (p = 0.0001), mitotic count (p = 0.0001), and histologic type (low-grade ESS vs leiomyosarcoma vs carcinosarcoma vs high-grade ESS, median: not reached vs 27 months vs 21 months vs 16.5 months, p = 0.0011), but not to postoperative therapy and patient age. The Cox model revealed that tumor stage, mitotic count and histologic type were independent prognostic variables for survival. In detail, the risk of death was significantly lower for low-grade ESS (risk ratio [RR] = 0.257; 95% confidence interval [CI] = 0.071-0.931) and carcinosarcoma (RR = 0.509; 955 CI = 0.324-0.799) when compared to leiomyosarcoma. Conversely, no significant difference in survival was found between leiomyosarcoma and high-grade ESS. CONCLUSIONS: Histologic type is an independent prognostic variable for survival in uterine sarcomas. Low-grade ESS has the best clinical outcome, whereas leiomyosarcoma has the poorest one. It is noteworthy that, when adjusting for stage and mitotic count, leiomyosarcoma has a significantly worse prognosis than carcinosarcoma.

Analysis of treatment failures and survival of patients with fallopian tube carcinoma: a cooperation task force (CTF) study.

OBJECTIVE: The objective of this retrospective multicenter study was to assess the pattern of failures and survival of patients with primary carcinoma of the fallopian tube. METHODS: The hospital records of 88 patients with primary carcinoma of the fallopian tube were reviewed. Surgery was the initial therapy for all patients. Tumor stage was I in 21 (23.9%), II in 21 (23.9%), III in 43 (48.8%), and IV in 3 (3.4%) patients. Postoperative treatment was given without well-defined protocols. The median follow-up of survivors was 55 months (range, 7-182). RESULTS: Of the 21 patients with stage I disease, 10 had no postoperative treatment and 11 had platinum-based chemotherapy. Five (23.8%) patients recurred after a median of 29 months (range, 8-93) from initial surgery. Of the 21 patients with stage II disease, 2 had no postoperative treatment, 2 underwent external pelvic irradiation, 16 received platinum-based chemotherapy, and 1 patient had oral melphalan. Eight (38.1%) patients recurred after a median of 25.5 months (range, 7-57). Of the 46 patients with stage III-IV disease, 1 patient refused chemotherapy and died after 19 months and 45 patients received platinum-based chemotherapy. A clinical complete response was obtained in 29 (64.4%) patients and a partial response in 8 (17.8%). A second-look laparotomy was performed in 14 of the 29 clinically complete responders: 12 patients were found to be in pathological complete response and 2 had persistent disease. Six (50.0%) of the former recurred after a median of 22 months (range, 13-101) from initial surgery. The two patients with persistent disease developed tumor progression after 15 and 11 months, respectively. Fifteen clinically complete responders did not undergo second-look, and 7 (46.7%) of them had a recurrence after a median of 18 months (range, 9-41). For the whole series, 5-year survival was 57%. By log-rank test, survival was related to FIGO stage (III-IV vs I-II, P = 0.0001), tumor grade (G3 vs G1 + G2, P = 0.0038), and patient age (>58.5 years vs <58.5 years, P = 0.0069), but not to histological type. The Cox model showed that FIGO stage (P = 0.0018) and patient age (P = 0.0290) were independent prognostic variables for survival. Among the patients with stage III-IV disease, 5-year survival was 55% for the patients who had residual tumor <1 cm compared with 21% for those who had larger residuum (P = 0.0169). CONCLUSIONS: Primary carcinoma of the fallopian tube shares several biological and clinical features with ovarian carcinoma. However, when compared with the latter, fallopian tube carcinoma more often tends to recur in retroperitoneal nodes and distant sites. Stage, patient age, and, among patients with advanced disease, residual tumor after initial surgery represent important prognostic variables for survival.

Efficacy of the combination ethinyl oestradiol and cyproterone acetate on endocrine, clinical and ultrasonographic profile in polycystic ovarian syndrome.

This study shows the effect of a long-term treatment (60 cycles) with the ethinyl oestradiol/cyproterone acetate pill, and the follow-up after 6 months from cessation, in polycystic ovarian syndrome. The 140 studied women had polycystic ovaries and moderate or severe acne, 108 also presented hirsutism. The endocrine profile significantly modified after six cycles (P < 0.001), with a further significant decrease of gonadotrophins, oestrogens and androgens after 12 cycles, and a greater increase of sex hormone-binding globulins and insulin-like growth factor-binding globulins. Between the 12th and 60th cycle there was only a significant reduction of dehydroepiandrosterone sulphate (P < 0.05). Acne disappeared in all patients within 12-24 cycles, but hirsutism was still present in 30.6% after 60 cycles. Mild-moderate hirsutism disappeared in 36-60 cycles, whereas severe hirsutism substantially decreased, but persisted. Ovarian volume, microcyst numbers and stroma percentage significantly decreased (P < 0.01). After 6 months from the end of the therapy, endocrine parameters were identical to the starting ones, acne and hirsutism reappeared, whereas ovarian morphology was between the initial and final condition. Ovaries were polycystic in 42 (30%) patients and multifolliculars in 98 (70%). Our results show the effectiveness of this combination on androgenic symptoms, especially on acne, and suggest that acne and hirsutism are induced by different peripheral mechanisms.

[Reciprocal supraventricular paroxysmal tachycardia in pregnancy. Apropos of a case]. / Tachicardia parossistica sopraventricolare reciprocante in gravidanza. A proposito di un caso.

The authors report a case of paroxysmal supraventricular reciprocal tachycardia, associated with transient Wolff-Parkinson-White syndrome in a 25-year-old woman, without heart disease, at 31 weeks gestation. The arrhythmia was successfully converted to sinus rhythm by intravenous flecainide. After delivery the arrhythmia and pre-excitation syndrome spontaneously disappeared and were not observed yet during the 6 months follow-up. Pregnancy may predispose patients with Wolff-Parkinson-White syndrome toward paroxismal supraventricular reciprocal tachycardia. The management of a similar case is discussed.

[Myocardial infarction caused by accidental electrocution. Apropos of a case with an 8-year follow-up]. / Infarto miocardico da elettrocuzione. A proposito di un caso seguito per 8 anni.

We report on a case of non-fatal myocardial infarction (MI) after electrocution. The diagnosis was made on the basis of electrocardiographic and enzymatic changes and was supported by the results of two-dimensional echocardiogram and radio-nuclide scans, showing segmental hypoperfusion and wall motion abnormalities. The patient was followed for over 8 years, evaluating the evolution of cardiac damage with the above tests. MI associated with electrical injury is very likely overestimated, owing to the low specificity of classical diagnostic criteria, such as ECG changes and CK-MB elevation, and the short monitoring of survivors. We suggest that non-invasive functional methods, exploring myocardial perfusion and ventricular kinesis, and a longer follow-up can reliably assess the prevalence of this complication.

[Ventricular fibrillation during stress test on a treadmill. Apropos of a case]. / Fibrillazione ventricolare durante prova da sforzo al tappeto rotante. A proposito di un caso.

A case of ventricular fibrillation occurring in the recovery phase of treadmill exercise test is described. A 64-year-old man was admitted to the hospital because of chest pain. The resting electrocardiogram was normal, but during a stress test (Bruce protocol) ventricular ectopic beats and ischemic S-T depression were observed. The echocardiogram showed septal hypertrophy and septal and apical hypokinesia. Ten days later he, during antianginal therapy, underwent treadmill exercise testing. In contrast with the previous stress test, ventricular ectopic beats decreased during the effort, but the S-T segment depressed, at the third step, with mild chest pain and hypotension. While angina and electrocardiogram improved, suddenly ventricular fibrillation developed. The patient was successfully resuscitated with electrical defibrillation, with a 350 joules shock. Echocardiogram was unchanged; serum enzymes were slightly modified (secondary to DC-shock). The ischemic changes observed at the electrocardiogram in the anterior wall within seven days returned in the normal range. Ten days later the patient underwent cardiac catheterization. At ventriculography the posterior and diaphragmatic wall was diskinetic, ejection fraction was 70%; a complete occlusion of the right coronary artery at the origin, a critical stenosis of left descending artery, with occlusion in the middle tract were found. Circumflex artery was occluded at the origin with omo-etero-coronary collateral channels. Twenty days later, he had a successful bypass surgery. Postsurgical echocardiogram revealed a moderate depression of ejection fraction (41%), inferior diskinesia, apical hypokinesia, mild mitral regurgitation. The patient was discharged with digitalis, nitrates, aspirin and amiodarone for prophylactic treatment of paroxystic atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

[The emergency treatment of supraventricular tachyarrhythmias: the efficacy and safety of intravenous propafenone]. / II trattamento d'emergenza delle tachiaritmie sopraventricolari: efficacia e sicurezza del propafenone endovena.

One hundred patients, admitted to the Emergency Unit for paroxysmal supraventricular tachycardia (SVT) with 1:1 AV conduction, atrial fibrillation (af) and flutter (AF) of recent onset (less than 72 hours) were treated with intravenous propafenone (P). The drug was administered at the dose of 70 mg over 5 min, repeated after 10 min if sinus rhythm (SR) was not restored and eventually followed by continuous infusion (0.35-0.50 mg/min) until conversion to SR or during the next 48 hours. Exclusion criteria were ventricular rate < 100/min, R-R intervals > 1 s, clinical signs of heart failure or asthma. Termination of SVT within 30 min was obtained in 94% of the patients, while reversion to SR occurred in 79% with af and in 55% with AF. For af and AF conversion was achieved within 30 min in 49% of overall responders (R), between 30 min and 6 hours in 27% and between 6 hours and 48 hours in 24%. The efficacy of P was significantly influenced by the duration of arrhythmia and left atrial size, measured by 2D-echocardiography. On the contrary, no difference was observed between R and non-R in mean age and in the percentage of primary or relapsing arrhythmias. Adverse effects were encountered in 7 patients: in 1 case worsened arrhythmia and in 6 patients, with long-lasting arrhythmias, congestive heart failure. Neither conduction disturbance nor extra-cardiac complications occurred. In conclusion, P provides effective and safe treatment for paroxysmal atrial tachyarrhythmias, so that it can be considered among the drugs of first choice even in non-intensive care units.

[Paroxysmal tachycardia in children: analysis of two clinical cases]. / Tachicardie parossistiche in età infantile: analisi di due casi clinici.

Two cases of paroxysmal supraventricular tachycardia in children are reported. Associated congenital heart disease were excluded by color-doppler echocardiogram. Electrocardiogram, holter monitoring and transesophageal study (in one case) suggested associated Wolf-Parkinson-White syndrome. The former case was successfully treated with digitalis, the latter, diagnosed "at risk" by transesophageal recording, was long term treated with propafenone. Clinical evaluation at follow-up confirmed the efficacy of the therapy.

Intravenous administration of alpha-1-proteinase inhibitor in patients of PiZ and PiM phenotype. Preliminary report.

Nine patients with moderate pulmonary emphysema, six of PiZ phenotype and three of PiM phenotype, have received a single intravenous infusion of alpha-1-proteinase inhibitor (human) (A1PI), in a dose of 60 mg/kg over a 30-minute period. They also received a tracer dose (300 microCi) of 131I-labeled A1PI. No active or passive immunization against hepatitis was given. No acute toxicity was observed. Compared with baseline data, significant elevations of serum A1PI (measured both antigenically and as anti-elastase activity) occurred, with a serum half-life approximating 110 hours. Bronchoalveolar lavage fluid, obtained 48 hours after infusion, reflected a significant increase in A1PI concentration versus baseline bronchoalveolar lavage fluid values. Serial gamma camera images of the lungs confirmed persistence of enhanced lung radioactivity for several days. Urinary desmosine excretion did not change following A1PI infusion. During the period of follow-up thus far, no patient has had chronic toxicity, results of liver function tests have been stable, and there has been no development of hepatitis B antigen or antibodies to hepatitis B surface or core antigens.

Preoperative identification and evaluation of the patient with lung disease.

Preoperative pulmonary function evaluation begins with the bedside, clinical identification of the presence of significant lung disease. Once a patient is so identified, preoperative pulmonary-function studies are indicated. The optimal screening studies for most patients are spirometry and arterial blood gas analysis. Patients who are identified as having marginal function by screening techniques should be studied further by more specialized studies, including radioisotopic evaluation of regional lung function. If a patient is identified as an operative candidate, but one who has increased risk of postoperative morbidity, prophylactic measures should be instituted to reduce postoperative complications. The essence of such measures is increased care preoperatively, intraoperatively, and postoperatively. The use of preoperative evaluation of pulmonary function presents a different magnitude of problem in defining the risk of morbidity in contrast to that of mortality. Available data provide a firm basis for the identification of the patient at increased risk of morbidity. After 23 years and dozens of spirometric studies involving thousands of patients, it is apparent that there is no spirometric number, percentage, or category that will absolutely separate the operable from the inoperable patient. There are estimates of risk--guidelines, to be sure--but no absolutes. The patient whose lung function would have been considered to prohibit lung resection in the 1950s has been successfully operated on in the 1980s. In dealing with the risk of mortality, the physician should always bear in mind that, although statistics apply to groups, they often do not apply to individual patients.

Cheyne-Stokes breathing during sleep in patients with left ventricular heart failure.

Fifteen patients with left ventricular heart failure (LVF) without known breathing disorders during sleep had full-night recordings of sleep and breathing to study the incidence and impact of the apnea of Cheyne-Stokes breathing. This group showed a marked degree of sleep-related breathing abnormalities, 40% demonstrating Cheyne-Stokes breathing with five or more central apneas per hour of sleep. Cheyne-Stokes breathing during sleep in patients with LVF predicted an increased short-term mortality rate. All six patients with LVF and Cheyne-Stokes breathing with more than five apneas per hour of sleep were dead within six months, while only three of nine patients without recurrent apnea died within six months, a significant difference (P less than .05) even in this small group. Among seven patients with LVF studied with the polysomnogram, there were statistically significant differences between the Cheyne-Stokes and non-apnea groups in total sleep time, awakening per hour, and the number of arterial desaturations. Although sleep disturbances have been anecdotally described in patients with LVF, no previous investigation has determined the incidence and impact of Cheyne-Stokes breathing during sleep in LVF. Our findings that Cheyne-Stokes breathing predicts an adverse short-term mortality rate confirm the clinical impression that Cheyne-Stokes breathing is a poor prognostic sign in LVF.

The effect of short-term oxygen supplementation on oxygen hemoglobin affinity in patients with chronic obstructive pulmonary disease.

In 12 hypoxemic patients with chronic obstructive pulmonary disease, the partial pressure of oxygen at which hemoglobin is 50% saturated (P50) and levels of 2,3-diphosphoglycerate (2,3-DPG) were determined under 3 study conditions: (1) while breathing room air, (2) during oxygen supplementation for 72 h sufficient to increase PaO2 above 70 mmHg, and (3) at 72 h after the period of oxygen supplementation. The data showed that in the control period in hypoxemic (PaO2, 52 +/- 6 mmHg), mildly hypercapnic (PaCO2, 47 +/- 6 mmHg) patients with a borderline elevation of pH (7.42 +/- 0.03), there was an increase in P50 (28.6 +/- 1.6 versus a normal value of 26.5 +/- 1; p less than 0.005), and a concomitant increase in 2,3-DPG (19.02 +/- 1.77 mg/g Hb versus a normal value of 13.52 +/- 1.27; p less than 0.005). Nine patients received oxygen for 24 h, and 5 received oxygen for 72 h. In these 5 patients, oxygen supplementation resulted in a shift in P50 to a normal value of 26.7 +/- 1.8 (this value was different from the patients' level while breathing room air and not different from that of the normoxemic control subjects) and a decrease in 2,3-DPG toward but not to a normal value (16.34 +/- 1.92; p less than 0.01). This shift in P50 to the left could be related to the decrease in 2,3-DPG. Accordingly, in patients with COPD who are treated with supplemental oxygen, the net effect on oxygen transport would be a function of the changes produced in PaO2 versus those in hemoglobin-oxygen affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoxemia during apnea in normal subjects: mechanisms and impact of lung volume.

Seven normal awake males were studied to define the mechanisms and impact of lung volume on the hypoxemia occurring during apnea. During repeated 30-s voluntary breath holding, these subjects were studied at different lung volumes, during various respiratory maneuvers, and in the sitting and supine body positions. Analysis of expired gases and arterial O2 saturation during these repeated breath holdings yielded the following conclusions. Apnea of 30-s duration at low lung volumes is accompanied by severe arterial O2 desaturation in normal awake subjects. Initial lung volume is the most important determinant of hypoxemia during apnea. The hypoxemia of apnea at most lung volumes can be explained by simple alveolar hypoventilation in a uniform lung. The lung does not behave as a single-compartment model at lung volumes at which dependent airways are susceptible to closure.

Determining changes in airway caliber in asthma: the role of submaximal expiratory flow rates.

Sixteen patients with suspected reversible airway obstruction who had previously demonstrated an increase in specific airway conductance after isoproterenol, but who had not demonstrated an increase in forced expiratory flow were studied using a measurement of submaximal flow. Flow during tidal breathing (VTV) was measured spirometrically, and VTV increased in all 16 patients from a value of 0.61 L/sec before isoproterenol to 0.80 L/sec after isoproterenol. In addition, each of these 16 patients experienced a significant increase in vital capacity and a significant decompression of functional residual capacity after isoproterenol. If plethysmography is not available, the measurement of VTV may provide evidence of bronchodilatation. The mechanism responsible for the dichotomy between maximal and submaximal flow is the compression of airways by high positive pleural pressure which is present during maximal, but not submaximal maneuvers.