Novel anticoagulants for stroke prevention in patients with atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia that can potentially result in stroke. Vitamin K antagonists (VKA) like warfarin were for many decades the only oral anticoagulants available for stroke prevention in patients with non-valvular atrial fibrillation (AF) at high risk of stroke. Recently, new oral anticoagulants (NOACS) have been introduced that act via direct inhibition of thrombin (dabigatran) or activated factor X (edoxaban, rivaroxaban and apixaban). Unlike VKAs, these anticoagulants do not require routine INR monitoring and posses favorable pharmacological properties. NOACs act rapidly, and have a stable and predictable dose-related anticoagulant effect with few clinically relevant drug-drug interactions. Phase III trials comparing these agents to warfarin for stroke prevention in patients with non-valvular AF demonstrated that they are at least as efficacious and safe as warfarin. Evolution of clinical guidelines to incorporate the new anticoagulants for stroke prevention in non-valvular AF may result in a reduction in the incidence of AF-related strokes. Safe and effective use of these new drugs in clinical practice requires understanding of their distinct pharmacological properties.

Metabolic and hemodynamic features of elderly patients undergoing beating heart coronary artery bypass graft surgery.

AIM: Coronary artery bypass graft (CABG) surgery, nowadays, is increasingly performed in patients who are older and have more comorbidities than subjects operated on a decade ago. In this study, we investigated metabolic and hemodynamic features of elderly patients with single vessel coronary artery disease (CAD), undergoing beating heart coronary artery bypass graft (BHCABG) surgery. METHODS: Twenty-five elderly patients, ages 73-78 years, with isolated left anterior descending artery (LAD) disease, were enrolled and compared to a younger similar group of 25 patients, mean age 48+/-1.2 years. A single vessel left internal mammary artery (LIMA) to LAD BHCABG was performed in all patients. Duration of temporary LAD occlusion was 9.8+/-0.5 min in the elderly group, and 10+/-0.4 min in the younger group. Myocardial arterial-venous differences in glucose, lactate, and creatine phosphokinase (CPK) were performed at different time points: preoperatively in the operating room (T0); at the end of the grafting procedure (T1); and before closing the chest (T2). Left ventricular stroke work index (LVSWI), as an indicator of global function of left ventricle, were recorded at T0, T1, T2, 6 (T3) and 48 (T4) hours postoperatively. RESULTS: Preoperative glucose extraction, observed in both groups, did not augment during and after surgery. In addition, neither lactate nor CPK were released in the coronary sinus during temporary LAD occlusion and following reperfusion in either group. Similarly, no significant changes in LVSWI were observed intra- and perioperatively between the two groups. CONCLUSIONS: Cardiac metabolism, hemodynamic parameters and global left ventricular function were not affected in either group by brief LAD occlusion during BHCABG, suggesting that BHCABG is a well-tolerated surgical approach, which can be safely attempted in patients of any age.

Use of octreotide, a long-acting somatostatin analogue, in the treatment of chylothorax of idiopathic etiology.

We describe a case of chylothorax of idiopathic etiology, treated with octreotide, a long-acting somatostatin analogue. A 30-year-old man with a left supraclavicular mass, and chylothorax, initially diagnosed by outpatient thoracentesis, underwent diagnostic surgery to ascertain the etiology of the pleural effusion. Biopsies of the left supraclavicular mass, lymphatic tissue and lymph nodes were benign. Triglyceride level in the pleural fluid was 396 mg/dL, diagnostic of chylothorax. Treatment included intravenous total parenteral nutrition (TPN) and a nil per os (NPO) diet. Subsequent surgical interventions included left lung decortication and glue-mediated control of chylothorax, combined with TPN and a strict low-fat diet. Given the persistency of chylothorax, thoracic duct ligation was also performed, and octreotide subcutaneous injections were started, with dramatic resolution of pleural effusion, after 1 week of treatment, in absence of any side effects. The patient fully recovered, and no relapse has been observed during a follow-up period of over 1 year. In conclusion, octreotide showed to be a valid and safe noninvasive approach for the treatment of chylothorax, whose early clinical use may also reduce the need for surgical intervention.

Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer.

PURPOSE: Topotecan and paclitaxel were evaluated in a randomized, multicenter study of patients with advanced epithelial ovarian carcinoma who had progressed during or after one platinum-based regimen. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 112) or paclitaxel (175 mg/m2) infused over 3 hours every 21 days (n = 114). Patients had bidimensionally measurable disease and were assessed for efficacy and toxicity. RESULTS: Response rate was 23 of 112 (20.5%) in topotecan-treated patients and 15 of 114 (13.2%) in paclitaxel-treated patients (P = .138). Disease stabilization for at least 8 weeks was noted in 30% of patients with topotecan and 33% of patients with paclitaxel. Median durations of response to topotecan and paclitaxel were 32 and 20 weeks, respectively (P = .222) and median times to progression were 23 and 14 weeks, respectively (P = .002). Median survival was 61 weeks for topotecan and 43 weeks for paclitaxel (P = .515). Response rates for topotecan and paclitaxel were 13.3% versus 6.7% (P = .303) in resistant patients (not responded to prior platinum-based therapy or progressed within 6 months of an initial response) and 28.8% versus 20.0% (P = .213) in sensitive patients (progressed > 6 months after response). Neutropenia was significantly more frequent on the topotecan arm 79% versus paclitaxel arm 23% (P < .01). It was short-lasting and noncumulative in both arms. Nonhematologic toxicities were generally mild (grades 1 to 2) for both agents. CONCLUSION: Topotecan has efficacy at least equivalent to paclitaxel manifested by the higher response rate and significantly longer time to progression.

Weekly cisplatin given for 2 months versus cisplatin plus cyclophosphamide given for 5 months after cytoreductive surgery for advanced ovarian cancer.

PURPOSE: To compare the efficacy of a treatment with cisplatin plus cyclophosphamide given for 5 months and a short treatment with cisplatin alone in advanced ovarian cancer, we conducted a multicenter randomized clinical trial. PATIENTS AND METHODS: Eligibility criteria were as follows: first diagnosis of histologically confirmed invasive epithelial ovarian cancer of International Federation of Gynecology and Obstetric (FIGO) stage III-IV, age younger than 75 years, and Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Within 28 days of cytoreductive surgery, eligible women were randomly assigned treatment with weekly cisplatin 50 mg/m2 for nine courses or cisplatin 75 mg/m2 plus cyclophosphamide 750 mg/m2 every 21 days for six courses. RESULTS: A total of 607 women were entered onto the study. There was no difference in the response to treatment. Pathologic complete response (CR) was documented in 63 of the weekly cisplatin cases and 70 of the cisplatin plus cyclophosphamide group (chi 1(2) = 1.43; P = .23). The median follow-up time was 3 years. There were 151 and 148 deaths in the weekly cisplatin and cyclophosphamide plus cisplatin arms, respectively. Survival curves were similar in the two groups, with a 3-year percent survival estimate of 44.1 (SE = 3.4) in the weekly cisplatin and 44.6 (SE = 3.4) in the cisplatin plus cyclophosphamide group (log-rank test chi 1(2) = 0.004; P = .96). CONCLUSION: This study found that 2-month monochemotherapy treatment with cisplatin was as effective as 5-month polychemotherapy including cisplatin at a similar doses but different dose-intensity plus cyclophosphamide.

Clinical evidence for topotecan-paclitaxel non--cross-resistance in ovarian cancer.

PURPOSE: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non-cross-resistance between these two compounds. PATIENTS AND METHODS: Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m(2)/d) x 5 every 21 days (n = 112) or paclitaxel (175 mg/m(2) over 3 hours) every 21 days (n = 114). A total of 110 patients received cross-over therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy. RESULTS: Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P =.638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients). CONCLUSION: Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non-cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.

Surgical second look in ovarian cancer: a randomized study in patients with laparoscopic complete remission--a Northeastern Oncology Cooperative Group-Ovarian Cancer Cooperative Group Study.

PURPOSE: The usefulness of extensive and repetitive surgery for patients with ovarian cancer still remains unproven (at least for some conditions). We planned an accurate prospective test of the hypothesis that patients with advanced-stage disease, after they had reached a clinical complete remission (CR), may benefit from surgical second look (SSL). PATIENTS AND METHODS: One hundred two patients in CR (as assessed by clinical findings, markers, and visualization by computed tomographic [CT] scan and laparoscopy), after initial debulking and first-line chemotherapy, were randomized to two arms, which were well balanced for predictive criteria such as age, stage at presentation, histology, grading, date of randomization, and residua after first surgery. Forty-eight patients were randomly assigned to receive follow-up evaluation only, while 54 were assigned to receive second surgery (eight of them refused). Of 46 surgical patients, 35 had negative and 11 positive surgical findings (24% clinically false-negative). RESULTS: Despite the microscopic residua found at open surgery, and the fact that the patients were then treated with second-line chemotherapy, SSL did not increase the probability of survival in this setting. In an analysis of the results according to the intention-to-treat criteria, after a 60-month follow-up period, the overall survival rates in the two groups of patients (SSL v no SSL) were 65% and 78%, respectively (P = .14). Multivariate analysis according to predictive criteria confirmed there was no significant difference between the two groups (P = .39). CONCLUSION: Our study shows the following: (1) our second-line treatment is scarcely effective; (2) SSL accurately defines complete responders to first-line chemotherapy; (3) SSL per se does not prolong survival; and (4) if confirmed, a less invasive procedure could replace SSL as a valuable method in new first-line regimens in ovarian cancer patients with clinical CR confirmed by laparoscopy.

Determination of tamoxifen and its metabolites in the endometrial tissue of long-term treated women.

Concentrations of tamoxifen and its metabolites were analysed in the endometrium of 23 post-menopausal asymptomatic breast cancer patients who were on chronic tamoxifen therapy. Small endometrial samples were collected during diagnostic hysteroscopy. Analysis of both serum and tissue for these compounds was performed by mass spectrometry. Tamoxifen and its metabolites were far more concentrated in the endometrium than in serum; tamoxifen was also significantly more concentrated in endometrium with hyperplastic changes than in atrophic endometrium. Endometrial polyps of an additional 9 women showed a trend to a lesser concentration of compounds. Increased concentration of tamoxifen compounds could possibly be explained by the avidity of these compounds for oestrogen receptors (ER).

Nonclosure of peritoneum at radical abdominal hysterectomy and pelvic node dissection: a randomized study.

OBJECTIVE: To compare closure and nonclosure of the peritoneum at radical abdominal hysterectomy and pelvic node dissection with respect to postoperative morbidity. METHODS: Women with uterine cancer who underwent radical abdominal hysterectomy and node dissection type II or III of Piver-Rutledge were assigned randomly to have a standard closure of pelvic and parietal peritoneum and placement of a T-shaped suction drain or to have the peritoneum left open but the vagina closed and two abdominal drains placed. Adjuvant radiotherapy was given to patients with risk factors. The postoperative incidence of lymphocysts (within 8 weeks from the operation and after 1 year) and infection-related and non-infection-related complications were analyzed. RESULTS: One hundred twenty subjects were enrolled, of whom 59 had peritoneal closure and 61 did not. Both groups were similar with regard to age, weight, nodes removed, nodal metastases, operative time, type of surgery, need for transfusion, and incidence of postoperative radiotherapy. The median follow-up was 36 months (range 11-72). Eleven patients died, four because of treatment-related complications. The amount of drainage was significantly higher in the closed group than in the unclosed group (median 740 mL, range 50-5980 versus median 340 mL, range 40-4000; P < .005). The incidence of asymptomatic lymphocysts was similar in the closed and open groups at 2 weeks (17 of 59 versus 15 of 6, respectively), at 8 weeks (eight of 56 versus ten of 61, respectively), and after 1 year (one of 21 versus four of 22, respectively). No difference was found between closed and open groups in terms of symptomatic lymphocysts (one of 59 versus two of 61, respectively), wound and pelvic infection (seven of 59 versus 11 of 61, respectively), febrile morbidity (two of 59 versus 11 of 61, respectively), and obstruction (zero of 59 versus one of 61, respectively). CONCLUSION: Nonclosure of the peritoneum at radical abdominal hysterectomy and node dissection is not hazardous and is not associated with an increased incidence of infection- or adhesion-related complications.

Primary Hodgkin's disease of the vagina.

We describe a patient with primary Hodgkin's disease (HD) of the vagina presenting with stage IEB. To our knowledge, this is the first case reported so far. Based on morphological and immunophenotypic features, the HD was classified as nodular sclerosis subtype, "syncytial" variant. The patient, a 64-year old woman, received chemotherapy followed by radiation therapy. She is still disease-free 14 months after diagnosis.

Postoperative radiotherapy and surgery in stage I endometrial carcinoma: a 10-year experience.

BACKGROUND: Data from the literature show that the incidence of pelvic recurrences in poor prognosis endometrial carcinoma is significantly reduced by combined surgery and radiotherapy compared to surgery alone. METHODS: In this paper we analyze the results of the combined treatment surgery plus adjuvant Irradiation in patients with endometrial carcinoma with regard to survival, site of progression, and toxicity. The surgical treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pelvic and para-aortic node dissection was performed. RESULTS: The overall 5-year survival was 88%. Three patients had local failure. Ten patients with local control of disease had distant metastases and 2 had local and distant recurrences. CONCLUSIONS: Our experience confirms the data of the literature. Postoperative irradiation is a safe and well tolerated treatment which can achieve good local control in high-risk stage I endometrial carcinoma. The control of distant metastases remains an open issue.

Endometrial stage I carcinoma treated with surgery and adjuvant irradiation: a retrospective analysis.

AIMS AND BACKGROUND: Data from the literature show that the incidence of pelvic recurrences in poor prognosis endometrial carcinoma is significantly reduced by combined surgery and radiotherapy compared to surgery alone. METHODS: In this paper we analyze the results of the combined treatment surgery and adjuvant irradiation in patients with endometrial carcinoma with regard to survival, site of progression, and toxicity. The surgical treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy in 40 patients. Pelvic and para-aortic node dissection was performed in 19 patients and lymph node sampling in 5. RESULTS: Overall 5-year survival was 85%. One patient had local failure, and 5 patients with local control of disease had distant metastases. Toxicity was mild and transient. CONCLUSIONS: Our experience confirms the data of the literature. Postoperative irradiation is a safe and well-tolerated treatment that can achieve a good local control in high risk, stage I, endometrial carcinoma. The control of distant metastases remains an open question.

Ovarian cancer: ten-year experience in a community hospital.

We reviewed 187 patients with epithelial ovarian cancer treated, from 1975 to 1985, at the Division of Radiotherapy and Medical Oncology, Pordenone General Hospital, Italy. It seemed of interest to report an experience carried out in a community hospital in a consecutive unselected series of patients affected by ovarian cancer. Survival time was evaluated from the day of the primary surgical approach to the end of the study (March 1985). The aim of the study was to confirm in our patient population the importance of some already recognised prognostic factors that influence survival (age, stage, histology, grade, type of surgery and residuum). We also analyzed the effect of the treatment variables chemotherapy and radiotherapy on survival. The general pattern of prognostic factors appears to be in agreement with reports in the literature. In our experience, residual disease and stage were the main important prognostic factors; grade and histology had a secondary relevance, and age did not seem to be a prognostic factor in our population. New chemotherapy regimens and/or radiotherapy did not appear to improve survival. In fact, comparison of the results obtained from 1975-1979 and from 1980-1985 (when more aggressive surgery and cisplatin-containing regimens were employed) showed no statistically significant difference in survival rate. Our data suggest that patients at an early stage can receive a satisfactory quality of care in a general hospital with oncology facilities, provided the surgeon and the pathologist are experienced in ovarian cancer. Patients at stage III but completely surgically resected can also be adequately treated. Patients with advanced disease, considering the lack of established efficacious treatments, should be referred to specialized centers, where new drugs or experimental strategies can be tested.

Squamous cell carcinoma in ovarian endometriosis. A case report.

A primitive squamous cell carcinoma of the ovary arose in ovarian endometriosis. The patient underwent a radical hysterectomy and radiotherapy. The other few similar reported cases had a poor prognosis. In our case the patient died 11 months after surgery.

Squamous intraepithelial cervical lesions in human immunodeficiency virus-seropositive women.

OBJECTIVE: To evaluate the relationship between human immunodeficiency virus (HIV) infection, CD4 serum level, cervical squamous intraepithelial lesions (SILs) and risk factors for human papillomavirus (HPV)-related dysplasia in HIV-positive women. STUDY DESIGN: All 51 eligible patients who were seen at the Colposcopic Outpatient Service, Aviano Cancer Center, Aviano, Italy, from July 1, 1993, to June 30, 1994, were studied for risk factors for HPV and HIV infection and had cervical cytologic smears, colposcopy with cervical biopsy and a serum CD4 count. RESULTS: Thirty of 51 patients (59%) had cytohistologically confirmed SIL. The prevalence of SIL was higher in HIV Centers for Disease Control stage IV disease than stages II and III (22/29 vs. 8/22 P < .05). There was no significant difference in the CD4 count between women with or without SIL (321 +/- 310 vs. 401 +/- 295/mm3 [mean +/- SD]). No relationship was found between CD4 count and severity of SIL (low grade SIL, 210 +/- 203/mm3; high grade SIL, 580 +/- 357/mm3). CONCLUSION: In our series there was no relationship between CD4 count and cervical SIL, suggesting that the expression of HPV-related dysplasia is a complex process in which risk factors for genital SIL play an important role, while the role of HIV must be defined again.

Surgical treatment of intestinal occlusions in advanced ovarian carcinoma.

The Authors report encouraging results concerning the surgical treatment of intestinal occlusions in 31 patients affected by advanced ovarian carcinoma. They stress the need for an increasingly accurate association of chemotherapy and aggressive surgery and underline the vital role that total parenteral therapy has to play in improving these results which are, nevertheless, satisfactory.

Hypogastric vein ligation during oncologic surgery as thromboembolic disease prevention.

Pulmonary embolism and vein thrombosis are frequent and dangerous complications in pelvic surgery. They can be the cause of death in 0.01%-0.87%. The Authors have used, since 1973, as vein thrombosis prophilaxis (VTP): early mobilization, physiotherapy, elastic compressive stocking plus pharmacologic therapy. Since 1975, according to Heidrich and Thomas researches, they have also adopted hypogastric vein ligation (HVL) in high risk patients, because those Authors underlined a primitive responsibility of the hypogastric district (mainly the left one). The Authors mortality rate after the introduction of HVL seemed very low. However, since Jan. '86, they have divided the high risk patients in 3 group (R), in order to collect statistically significant data in the usefulness of the proposed technique.

Different patterns of postoperative bleeding following cytoreductive surgery for gynecological cancer.

PURPOSE OF INVESTIGATION: To study the possible causes of postoperative bleeding following maximal cytoreductive surgery for gynecological cancers. METHOD: We have retrospectively reviewed all our cases of postoperative bleeding following major abdominal and pelvic cytoreductive surgery within a 48-hour period. In the postoperative period, replacement therapy was ineffective in achieving hemodynamic stability. During re-operation, the entire abdominal cavity was evaluated for bleeding sites that were adequately ligated or electrocoagulated. RESULTS: Of 942 women undergoing major cytoreductive surgery 22 women (2.3%) were re-operated for postoperative bleeding after a mean of 14.2 hours. Bleeding was either localized from a vessel in 9 women (40.9%) or diffuse (capillary oozing) in 13 women (59.1). Operative deaths have been as high as 36.8%. CONCLUSION: Postoperative bleeding following cytoreductive surgery can be from a single group of vessels or a capillary oozing from the edges or denuded areas of excised peritoneum.

[Local anesthesia in cervix biopsy]. / L'anestesia topica nelle biopsie della portio.

The Authors evaluated the perception of pain in a group of 35 patients undergoing cervical biopsy and the efficacy of using 40 mg of lydocaine (xylocaina spray) in 24 patients compared to a control group. Pain perception was evaluated using Scott-Huskissons's visual analogous scale. It was observed that this diagnostic method was painful and that premedication using topical anesthesia was an efficacious method of significantly reducing painful symptoms.

[Laser conization guided by endocervical staining with methylene blue]. / Conizzazione laser guidata mediante colorazione endocervicale con blu di metilene.

The authors report their experience of the use of a vital stain--methylene blue--as a surgical guide in laser cervical conization for CIN2-CIN3/CIS. During the period 1 October 1991-31 December 1992 a total of 40 laser cervical conizations were performed under local anesthesia using a CO2 laser connected to a microhandpiece and colposcope in patients with exo-endocervical lesions which were histologically positive for CIN2-CIN3/CIS. In 33/40 patients an aqueous solution of 1% methylene blue was introduced preoperatively in the endocervix using a cotton-wool bud with consequent impregnation of the pseudoglandular crypts: laser biopsy was performed along the guidelines of the stain itself. This enabled the direction of resection to be varied: in 3 patients due to an anomalous and eccentric direction of cervical canal; in 10 patients to remove glandular structures surrounding or underneath lesions; in 8 patients following pseudoglandular section to carry out deep vaporization (3 patients) or correct cutting edges (5 patients). The apex and edges of the cone were always intact. Fourteen patients completed a 12-month follow-up and a further 6 were followed up for 9 months; only 1/14 patients (with AIDS) showed recidivation after 1 year. In the authors' experience the use of a vital stain as a guide during laser cervical cone biopsy is an easily used method which ensures the greatest possible respect for healthy cervical structures, also in order to preserve fertility in young patients.