Patent ductus arteriosus in preterm infants: benefits of early surgical closure.

BACKGROUND: Patent ductus arteriosus in preterm neonates leads to significant morbidity. Surgery is indicated when pharmacological treatment fails or is contraindicated, but the optimal timing remains unclear. METHODS: We retrospectively studied all 41 preterm neonates with symptomatic ductus arteriosus who underwent ligation between 1988 and 2009. We compared early complications rates and late neurological outcomes of patients operated on before 21 days of age with these operated on later. RESULTS: The median gestational age at birth was 26 weeks (range 23-31 weeks) and median weight at birth was 930 g (range 510-1500 g); 34 (82.9%) received pharmacological treatment before surgery. Fourteen (34.1%) patients underwent surgical closure before 21 days of age and 27 (65.9%) after 21 days. The 2 groups did not differ significantly in gestational age and weight at birth, but those operated on after 21 days received significantly more pharmacological treatment cycles. Patients in the early closure group had shorter intubation times: median 23 days (range 13-35 days) vs. 43 days (range 27-84 days; p < 0.001) and shorter neonatal intensive care unit stay: median 44 days (range 31-66 days) vs. 76 days (range 41-97 days; p < 0.001), with significantly lower rates of bronchopulmonary dysplasia, intraventricular hemorrhage, and acute renal failure, and significantly better neurological outcomes. DISCUSSION: Performing early ligation of symptomatic ductus arteriosus after unsuccessful pharmacological therapy in preterm neonates might lower complication rates and improve neurological outcome. Prospective randomized studies are needed to determine the optimal treatment.

Inhaled nitric oxide for elevated cavopulmonary pressure and hypoxemia after cavopulmonary operations.

Background. Elevated cavopulmonary pressure early after surgical creation of cavopulmonary connections is an important hemodynamic problem with grave prognostic significance. We examined the effect of administration of inhaled nitric oxide (iNO) to patients with elevated cavopulmonary pressure in the early postoperative period. Methods. We retrospectively reviewed data pertaining to all 14 patients with superior (n = 6) and total (n = 8) cavopulmonary connections who were treated with iNO in the early postoperative period during an interval of six years. Changes in the cavopulmonary pressure, the transpulmonary gradient, and the oxygen saturation after the institution of iNO were evaluated. The preoperative characteristics of the patients were compared to those of a control group of patients with cavopulmonary operations not treated with iNO postoperatively. Results. Twelve hours after the initiation of iNO therapy, significant reduction in the cavopulmonary pressure (16.6 ± 3.5 mm Hg vs 18.1 ± 2.3 mm Hg, P = .006), reduction in the cavopulmonary gradient (7.0 ± 3.5 mm Hg vs 9.8 ± 3.7 mm Hg, P = .009), and elevation of the arterial oxygen saturation (84.5% ± 6.0% vs 78.7% ± 5.9%, P = .001) were observed. Linear correlation analysis confirmed tendencies for reduction in the cavopulmonary pressure (P = .13), reduction in the cavopulmonary gradient (P = .02), and elevation of the oxygen saturation (P = .10). Compared to the control group, the treated patients tended to have higher preoperative pulmonary arterial pressures (PAPs) 17 (11-30) mm Hg versus 12 (10-25) mm Hg, P = .10; higher pulmonary vascular resistance (PVR) 2.04 (0.27-6.94) Wood units versus 1.02 (0.49-5.20) Wood units, P = .37; and longer bypass times 154 (41-218) versus 91 (15-276) minutes, P = .13. Conclusions. Administration of iNO was associated with diminuition of cavopulmonary pressure and transpulmonary gradient and increasing oxygen saturation in our small group of patients. In our experience selected patients with preoperatively elevated PAP above 17 mm and PVR above 2 Wood units can undergo cavopulmonary operations with iNO treatment early postoperatively.

Left ventricular and mitral valve function long after repair of left anomalous coronary artery from the pulmonary artery: recovery years after severe ischemia.

BACKGROUND: The study evaluates the long-term results of surgery for anomalous left coronary artery from the pulmonary artery (ALCAPA) with special attention on the left ventricular (LV) function and mitral regurgitation. METHODS: Twenty-one children underwent surgery for ALCAPA over 23 years (1987-2010). All patients underwent establishment of a two-coronary system, by direct reimplantation (n = 13) or by intrapulmonary tunnel technique (n = 8), with concomitant mitral valve repair in one. The follow-up echocardiograms were evaluated to assess LV function and mitral regurgitation. RESULTS: Five patients died. The age of the nonsurvivors was lower, 4.2 ± 1.3 versus 22.7 ± 29.4 months, P = .04. All nonsurvivors had moderate or severe mitral regurgitation preoperatively and higher LV diameter z score than the survivors: 11.8 (9-14.6) versus 4.6 (1.9-13.1), P = .01. At last follow-up, all survivors were asymptomatic; the diastolic LV diameter was normal, with z scores: 0.3 (0.1-1.9) versus 7 (1.9-14.6) preoperatively, P = .001, as was the LV ejection fraction: 66% (61%-78%) versus 38% (16%-70%) preoperatively, P = .001. Fifteen patients had moderate or severe mitral regurgitation at initial presentation and it eventually regressed to insignificant in all survivors (P = .001). No subsequent interventions on the coronary arteries or the mitral valve were needed. Four patients with intrapulmonary tunnel had mild suprapulmonary obstruction with Doppler peak gradients between 20 and 30 mm Hg. CONCLUSIONS: In our experience, establishment of a two-coronary circulation without mitral valve repair leads to normalization of LV dimension and systolic function and to improvement of mitral regurgitation in the surviving patients. Mortality is related to low age and to the associated higher degree of LV dysfunction.

Prognostic factors and outcome in women with uterine sarcoma.

OBJECTIVES: A retrospective analysis of patients with uterine sarcoma was undertaken to assess prognostic factors and treatment related outcomes. PATIENTS AND METHODS: Ninety-four patients (median age: 60years, range: 20-93years) with a histologically verified uterine sarcoma treated at the McGill University Health Centre (MUHC) between 1989 and 2004 were identified from the tumor registry and pathology database. RESULTS: Twenty-eight patients had an endometrial stromal sarcoma (ESS), 30 had a leiomyosarcoma (LMS), and 36 had mixed muellerian tumors (MMT). According to FIGO classification, Stage I, II, III, and IV tumors were identified in 49, 7, 20, and 18 patients, respectively. At the time of analysis, 55.5% of patients (52/94) were dead due to progressive sarcoma disease; 8.5% of the patients (8/94) were alive with disease recurrence, and 36.2% (34/94) were alive without disease recurrence, with a median survival of 35months. Univariate analysis demonstrated a statistically significant association between overall survival and histology in favor of patients with ESS (p<0.001). Analyzing each of the histological subtypes separately, adjuvant treatment with chemotherapy and/or hormonal treatment had no demonstrable impact on overall survival. In multivariate analysis age and advanced stage, remained a significant predictor for overall survival in patients with LMS and MMT, but not in patients with ESS. Regarding adjuvant treatment, radiotherapy had a significant impact on overall survival only in patients with MMT (p=0.002). CONCLUSIONS: In patients with uterine sarcoma, in comparison to LMS and MMT, ESS tends to present as a less aggressive disease with a favorable outcome. Furthermore, reflected by an improved overall survival after radiotherapy only in patients with MMT, it seems to be mandatory to differentiate between these histological subtypes.

Primary malignant mesodermal ovarian sarcomas.

Primary malignant mesodermal ovarian sarcomas are rare tumors and have a poor prognosis. The disease is usually diagnosed at a late stage and 5-year survivals are uncommon. Most patients are treated with debulking surgery followed by adjuvant chemotherapy. We report ten patients treated at a single institution. All patients underwent surgery and 90% received adjuvant chemotherapy. The median survival was 20 months, and only one patient survived beyond 5 years. Newer treatment strategies are urgently needed in the management of this disease.

The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers--a study of the National Cancer Institute of Canada Clinical Trials Group.

A multicenter phase II trial was conducted to define the activity of letrozole in postmenopausal women with recurrent or advanced endometrial carcinoma, who had no more than one prior line of progestins and never had chemotherapy (except adjuvant). Archival paraffin-embedded tumor samples were retrieved to determine the expression level of estrogen (ER) and progesterone receptor (PgR), p53, HER-2, bcl-2 and PTEN protein, and phosphorylation status of protein kinase B (PKB/Akt). Thirty-two eligible patients were treated with letrozole at 2.5 mg daily continuously, of whom 10 (31%) had prior progestins. Of the 28 patients evaluated for response, one complete and two partial responses were noted; overall response was 9.4% (95% confidence interval 2-25%). Eleven patients had stable disease for a median duration of 6.7 months (range 3.7-19.3 months). Amongst 22 patients who had tumor blocks available, the proportion showing positive expression of the following markers includes: PgR (86%), ER (86%), PTEN (82%), phosphorylated PKB/Akt (59%), bcl-2 (45%), p53 (32%), and HER-2 (0%). None of these markers correlated with response to letrozole or disease progression. In conclusion, letrozole is well tolerated but has little overall activity in this cohort of women with endometrial cancer.

A phase II trial of mitomycin, ifosfamide and cisplatin in recurrent carcinoma of the cervix.

The purpose of this study was to evaluate the efficacy and the toxicity of mitomycin, ifosfamide, and cisplatin in patients with recurrent carcinoma of the cervix. Between July 1992 and March 1995, 20 patients with recurrent cervical cancer were enrolled in this study. No patients had received prior chemotherapy for metastatic disease, except some were exposed to cisplatin as a radiosensitizer at the time of their diagnosis. Mitomycin-C 6 mg/m2, ifosfamide 3 g/m2, and cisplatin 50 mg/m2 were given intravenously every 3 weeks. All patients were assessible for response and toxicity, and none was lost to follow-up. All patients except one had squamous cell carcinoma. The overall response rate was 45% (2 complete remissions and 7 partial remissions). The mean response duration was 35 months, and the median survival from treatment for the whole group was 14 months. Fifteen percent of all cycles produced grade 3 or 4 myelosuppression, and the main nonhematologic toxicity was nausea and vomiting, which was reported in 11.5% of all cycles. One death occurred secondary to chemotherapy-induced septicemia. Three patients are still alive, two with a complete response and one with a partial response. In conclusion, mitomycin, ifosfamide, and cisplatin have a good activity in recurrent carcinoma of the cervix and are comparable to other combination chemotherapy.

Human papillomavirus DNA in invasive cervical carcinomas and its association with patient survival: a nested case-control study.

This study sought to examine the association between the presence of human papillomavirus (HPV) DNA in invasive cervical cancer and prognosis. A case-control study was undertaken nested in a cohort of 208 patients with invasive cervical carcinoma in Montreal. All 40 deceased patients formed the case groups. A control group of equal size was selected by matching to each case (1:1) a patient of the same age and year of admission who had survived her disease. HPV DNA was detected by the use of a PCR protocol. The odds ratio (OR) for cervical cancer death was computed by logistic regression. Detection of HPV, particularly of types 16 and 18, was negatively correlated with disease stage and histological grade. The OR for death was 0.27 [95% confidence interval (CI), 0.1-0.8] for those whose tumors were positive for HPV DNA versus those in whom HPV DNA was not detected. After adjusting for the confounding effects of stage and grade, the prognostic effect was somewhat reduced, with an OR of 0.34 (CI, 0.1-1.1), which was no longer significant. The magnitude of the HPV-survival association was not altered when the analyses were restricted to carcinomas of stages I and II. Regardless of the mechanism for the prognostic role, detection of HPV DNA in primary tumors may play an important adjunct role in assessing prognosis of patients with invasive cervical cancer.

Biomechanical and clinical performance of a new synthetic monofilament absorbable suture.

The clinical and mechanical performance of a new, monofilament, synthetic absorbable suture (Biosyn) was evaluated and compared to that of a braided synthetic absorbable suture (Vicryl). The monofilament synthetic absorbable suture was significantly stronger than the braided synthetic absorbable suture over the 4 weeks of implantation. In addition, the monofilament suture potentiated less bacterial infection than did the braided suture. The handling characteristics of the monofilament suture were superior to the braided suture because the monofilament suture required fewer throws to achieve knot security, encountered lower drag forces in fascia and colon, and had a greater double-wrapped first-throw knot security. Evaluated independently in clinical settings, the monofilament sutures were found to have excellent strength, first-throw hold, knot security, passage through tissue, knot repositioning, and ease of handling.

Weekly cisplatin plus external beam radiotherapy and high dose rate brachytherapy in patients with locally advanced carcinoma of the cervix.

PURPOSE: Prospective, single arm, Phase I/II trial performed to assess the efficacy and toxicity of the concomitant use of weekly cisplatin and pelvic radiotherapy in patients with locally advanced carcinoma of the cervix. METHODS AND MATERIALS: Between December 1988 and April 1991, 50 previously untreated patients with bulky, locally advanced, squamous cell carcinoma entered the study. All patients were evaluated by a gynecologist and a radiation oncologist and were submitted to standard pre-treatment staging procedures. The International Federation of Gynecology and Obstetrics stage distribution was as follows: IIA three patients, IIB seventeen, IIIA two, IIIB 25, and IVA three. Radiotherapy consisted of 46 Gy external beam irradiation plus three high dose rate intracavitary treatments given on a weekly basis to a total dose of 30 Gy to point A. Cisplatin 30 mg/m2 was also given weekly starting on day 1 of radiotherapy. RESULTS: With a median follow-up time of 27 months, complete response was seen in 88% (44/50) of the patients. The actuarial survival rate at 44 months was 65%. Total pelvic failure rate was 26% (13/50). Of the 44 patients who achieved a complete remission, only seven have failed in the pelvis. Distant disease was observed in 24% of the cases. Treatments were well tolerated with no patient requiring an interruption in the radiotherapy. However, the incidence of late gastrointestinal toxicity was high, with 10 patients developing a rectal ulcer (four colostomies for severe bleeding), two patients a small bowel obstruction, and two patients a recto-vaginal fistula. Moreover, gastrointestinal complications appeared sooner than expected, at a median follow-up time of 11 months after completion of treatment. CONCLUSION: The combination of weekly cisplatin and radiotherapy appears to be a very effective regimen for patients with locally advanced carcinoma of the cervix, but resulted in a relatively high frequency of late gastrointestinal complications.

Ototoxicity due to cis-diamminedichloroplatinum in the treatment of ovarian cancer: influence of dosage and schedule of administration.

Ototoxicity associated with administration of cisplatin was assessed in four groups of patients suffering from advanced ovarian carcinoma. The purpose was to determine the influence of dosage, schedule of administration, and long-term treatment on pure-tone thresholds and other auditory parameters. One hundred and forty-five serial audiograms were obtained in 60 patients and compared with baseline audiograms. The treatment protocol consisted of two different dosages (low--50 mg/m2 and high--100 mg/m2) and three different schedules of administration (short--6 months, extended--12 months, and treatment in blocks--intervening months in which cisplatin was withheld). Using a conservative definition of auditory toxicity and statistical analyses of pure-tone threshold differences between groups, the results indicated that the low dose-short treatment regimens with either monthly administration of cisplatin, or administration in blocks, were the least ototoxic. Ototoxicity was found to increase with increasing cumulative dosages. Hearing loss was primarily in the high frequencies. The most severe ototoxic effects, which include tinnitus and hearing loss in the speech frequency range, were associated with the administration of high dosages over a short period of time. Individual variability in susceptibility to ototoxicity necessitates systematic audiometric monitoring throughout therapy.

Radiation therapy of primary vaginal carcinoma.

Primary carcinoma of the vagina is rare, constituting only 1 to 2% of all neoplasms arising in the female genital tract. From 1950-1974, 36 patients with carcinoma of the vagina were treated with radiation at Memorial Sloan-Kettering Cancer Center (MSKCC); 35 (96%) had epidermoid carcinoma and one patient (4%) had adenocarcinoma. These patients were staged according to FIGO. Fourteen patients (39%) were Stage I; six patients (17%) were Stage II; three patients (8%) were Stage III; and 13 patients (36%) were Stage IV. Nine patients (25%) were treated with external radiation and interstitial implant; seven patients (20%) were treated with interstitial implant alone; nine patients (25%) were treated with external radiation alone and 11 patients (30%) with external radiation and intracavitary radiation. The five year NED survival was 71% in Stage I, 66% in Stage II, 33% in Stage III and 0% in Stage IV. This paper discusses radiotherapy management of primary carcinoma of the vagina.