Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement: ABRAX international retrospective cohort study.

BACKGROUND: The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. PATIENTS AND METHODS: We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA-IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. RESULTS: The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799-1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458-1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690-1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. CONCLUSION: We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. CLINICAL TRIALS IDENTIFIER: NCT04037124.

Is adjuvant chemotherapy indicated in stage I pure immature ovarian teratoma (IT)? A multicentre Italian trial in ovarian cancer (MITO-9).

OBJECTIVE: Conservative surgery followed by platinum-based chemotherapy is considered the standard approach for stage I immature ovarian teratoma (IT), except for stage IA G1. Nevertheless the use of chemotherapy in stage IA G2-3 and IB-IC is controversial. The aim of this study was to evaluate the outcome of patients with IT in order to define the role of chemotherapy in stage I disease. METHODS: Twenty-eight patients with stage I IT treated in MITO centers were retrospectively reviewed. Grade, stage, age, surgical and postoperative treatment were analyzed using χ(2) test and T test looking for association with recurrence. RESULTS: Median age was 25.5. Twenty-four patients underwent fertility-sparing surgery. FIGO stages were 19 IA, 2 IB, and 7 IC. Nine patients had grade 1 tumor, 12 grade 2, and 7 grade 3. Nine patients received adjuvant chemotherapy. Overall recurrence rate was 21.4% (2 in chemotherapy group and 4 in the group without treatment). No patients with G1 had recurrence, whereas 25% of G2 and 42.9% of G3 relapsed. Recurrence rate was not significantly different according to stage, grade or adjuvant chemotherapy, whereas it was greater in the group not operated in a MITO center, not staged and of age lower than 20 years, with statistical significance. At recurrence 4 patients presenting with mature teratoma were treated with surgery alone, whereas 2 recurring with IT were treated with surgery plus chemotherapy. After a median follow-up of 59 months all patients are NED. CONCLUSIONS: Our study suggests that chemotherapy may be withheld for primary therapy and utilized only for recurrence.

Adnexal Torsion in Pediatric Age: Does Bolli's Score Work? Report of Two Cases.

Adnexal torsion is a surgical emergency requiring early diagnosis in order to avoid demolitive surgery. Adnexal torsion's diagnosis could be very difficult in pediatric patients because children cannot explain symptoms accurately. Furthermore reproductive organs lie high in abdomen, causing unclear examinations findings. For reducing diagnostic mistakes or delay clinical and hematological criteria could be useful. No radiological criteria (CT or MRI) should be taken in count because of the costs and the required time. By combining clinical presentation in patients with OT three useful diagnostic variables have been identified: age, duration of pain, vomiting. Presence of vomiting, short duration of abdominal pain and high CRP levels have great predictive value for the diagnosis of adnexal torsion. In those patients an exploratory laparoscopy should be performed without any doubt and/or delay. These data may aid physicians in the evaluation of abdominal pain in premenarchal girls.

Improving outcomes in tumour necrosis factor a treatment: comparison of the efficacy of the tumour necrosis factor a blocking agents etanercept and infliximab in patients with active rheumatoid arthritis.

AIM: The aim of this study was to evaluate the differences between infliximab and etanercept, in terms of clinical efficacy and rapidity of action. METHODS: We selected 32 patients with rheumatoid arthritis (RA) with an incomplete response to disease modifying anti-rheumatic drugs (DMARDs), and randomly assigned them to etanercept or infliximab. We evaluated the efficacy after 14, 22, 54 weeks of treatment, using the American College of Rheumatology (ACR) 20, 50 and 70 criteria, and the improvement of quality of life using the Health Assessment Question-naire (HAQ). RESULTS: After 14 weeks, the 54.4% of patients was considered ACR-responders in the etanercept group, whereas, in the infliximab group, the percentage of responders was 74.4%: infliximab gave better results for the tender joint count and for physician's global assessment. After 22 weeks, no significant difference was present. After 54 weeks, etanercept resulted more effective than infliximab for tender joint count (TJC) value, for visual analogic scale (VAS) for pain score, for global disease assessment value, with 74.4% of patients considered ACR-responders in the group treated with etanercept and 60% in the group treated with infliximab. As regards HAQ, patients in the infliximab group presented higher scores at week 14, but in weeks 22 and 54, patients in the etanercept group showed better results. Therefore, both infliximab and etanercept are efficacious in RA, but infliximab is more efficacious than etanercept in week 14. Vice versa, in week 54 etanercept is the most efficacious drug. CONCLUSIONS: Physicians have 2 weapons in their armamentarium, with the same target but distinct clinical, pharmacokinetic and pharmacodynamic properties.

Angioplasty increases coronary sinus F2-isoprostane formation: evidence for in vivo oxidative stress during PTCA.

OBJECTIVES: Isoprostanes, stable end-products of oxygen free radical mediated-lipid peroxidation, were measured in the coronary vessels during percutaneous transluminal coronary angioplasty (PTCA) to provide direct evidence for enhanced oxidative stress in a local milieu in vivo. BACKGROUND: Percutaneous transluminal coronary angioplasty is associated with complications such as myocardial stunning and accelerated restenosis, which at least in part are mediated by oxygen free radicals. Because isoprostanes are markers of oxidant stress and potent vasoactive compounds, the formation of which is not inhibited by aspirin treatment in vivo, it is possible that these mediators are increased locally during PTCA. METHODS: In 12 coronary artery disease patients who were given aspirin and ticlopidine, blood samples from coronary sinus were taken immediately before and immediately upon balloon deflation during PTCA. Isoprostane F2alpha-III, isoprostane F2alpha-VI, and TxB2 were quantified after extraction and chromatography using a stable dilution isotope gas chromatography/mass spectrometry assay. RESULTS: Coronary sinus and left main coronary artery levels of iPF2alpha-III and iPF2alpha-VI at baseline were (mean +/- SEM) 40 +/- 9 pg/ml and 115 +/- 10 pg/ml, respectively. The TxB2 levels were undetectable. Following PTCA, isoprostane levels markedly increased (mean +/- SEM): iPF2alpha-III, 125 +/- 12 pg/ml (p < 0.001); iPF2alpha-VI, 295 +/- 20 pg/ml (p < 0.001), whereas TxB2 levels remained undetectable. CONCLUSIONS: These results indicate that PTCA induces coronary sinus increase in F2-isoprostane formation, and they also provide direct evidence for enhanced oxidative stress in a local milieu in vivo. Thus, an increased F2-isoprostane formation could play a role in the pathogenesis of some PTCA-associated untoward events.

Ovarian cystic teratoma with primary epithelial cell melanoma.

We report a rare case of malignant melanoma arising in a cystic teratoma of the ovary occurring in a 60-year-old woman who died in four months despite the combined treatment administrated (surgery and chemotherapy). Diagnosis of ovarian melanoma was confirmed by immunohistochemical positivity to S-100 protein and HMB 45. There was no evidence of extra-ovarian primary melanoma on clinical examination; therefore the diagnosis was primary ovarian melanoma. Melanoma metastases were detected on the uterus, the right ovary, the omentum and in one of the three excised left external iliac lymph nodes. A review of the literature is analyzed and discussed.

Rheumatic symptoms in patients with human immunodeficiency virus are related to levels of tumor necrosis factor-alpha but not to viral load.

Infection with human immunodeficiency virus (HIV) can lead to osteoarticular involvement, usually in the late stages. The pathogenesis of these symptoms has usually been attributed to viral load or to dysregulated cytokine production. We evaluated the presence of rheumatic symptoms and levels of tumor necrosis factor (TNF)-alpha viral load and CD4 count in 46 patients with HIV from southern Italy. The prevalence of rheumatic symptoms was 23.9%; CD4 count and viral load presented no statistically significant differences between patients with rheumatic symptoms and patients without osteoarticular involvement, whereas TNF-alpha levels were increased in HIV patients with arthralgias compared with those in patients without arthralgias (p = 0.02). Evidence that TNF-alpha is increased in patients with osteoarticular or soft tissue involvement is a clear index of the pivotal role this cytokine plays in the pathogenesis of these manifestations.

Isometric handgrip exercise increases endothelin-1 plasma levels in patients with chronic congestive heart failure.

This study demonstrated an immediate and short-lasting endothelin-1 release in the circulation of patients with severe chronic congestive heart failure during isometric handgrip exercise, but not in normal subjects. Our data suggest that endothelin-1 levels may increase transiently during daily physical activity, thus contributing to progressive deterioration of left ventricular function.

Acquired coronary-to-left ventricle fistula: evidence by myocardial contrast echocardiography.

The case report subject is a patient with an old anteroseptal myocardial infarction and postinfarction angina who developed, over the years, a small left coronary-to-left ventricle fistula. The first coronary angiogram, performed 4 months after the infarction, was negative for coronary fistula. The diagnosis was made 3 years later, at repeat cardiac catheterization with myocardial contrast echocardiography. Left and right coronary injections of 0.2 cc of sonicated 5% human albumin microbubbles generated a bright cloud of contrast entering the left ventricular cavity at the level of the distal third of the interventricular septum. Conversely, cineangiography failed to show on-line the fistulous communication that was evident only after careful cineangiographic reviewing. This case demonstrates the high efficacy of myocardial contrast echocardiography in identifying very small coronary fistulae.

Spontaneous left atrial echocardiographic contrast in mitral stenosis: early disappearance after valve replacement.

We describe a patient with mitral stenosis and severely enlarged left atrium. Transthoracic echocardiography showed a false image of intraatrial thrombus, whereas transesophageal echocardiography showed massive spontaneous left atrial contrast. Intraoperative transesophageal echocardiography was performed. During cardioplegic arrest the contrast was enhanced, but it gradually and completely cleared 15 minutes after cardiopulmonary by-pass arrest. Transesophageal echocardiography is a useful technique for the study of intraatrial masses and may bring a new dimension to tissue characterization studies.

Prolonged 5-fluorouracil infusion in patients with metastatic colon cancer pretreated with bolus schedule of the same agent.

5-Fluorouracil (5FU) is the most important drug in the treatment or gastrointestinal cancer. 5FU can be administered by bolus or continuous infusion. It seems that continuous infusion is capable of producing responses in patients pretreated with bolus of the same drug. To overcome drug resistance in metastatic colon cancer patients, we have administered (via programmable pump) 5FU by prolonged infusion with doses of 250 mg/m2/die for six weeks with a one week rest period. Twenty-one patients with disease progression following bolus 5FU leucovorin were enrolled. The treatment was well tolerated with mucositis (grade I-II) in five patients and hand-foot syndrome in four; these side effects were managed with brief interruption of the infusion. Four partial responses and six stable disease were obtained. Two patients are alive after 14 months. The data of this study suggest that it is possible to overcome acquired 5FU bolus resistance by use of different schedules of the same drug.

Twenty-four-hour pattern of atrial natriuretic peptide in heart transplantation: evidence for lack of circadian rhythm. Temporal inter-relationships with plasma renin activity, aldosterone and cortisol.

We have investigated the circadian rhythm of plasma atrial natriuretic peptide in 13 stable output heart transplanted patients, all without evidence of histological rejection and cardiac impairment, following antirejection therapy with Cyclosporine, Azathioprine and Prednisone. The 24-h pattern of plasma renin activity, plasma aldosterone and plasma cortisol has been studied as well. All the investigated variables were assayed six times over the 24-h span. The circadian time-qualified data were analyzed by ANOVA and Cosinor method. The 24-h mean levels of atrial natriuretic peptide, plasma renin activity and plasma aldosterone are significantly increased, while the concentrations of plasma cortisol are reduced in the heart transplanted recipients. ANOVA detected a significant within-day variability of all these humoral variables only in healthy subjects. A statistically significant circadian rhythm was validated by Cosinor procedure for all the investigated molecules in healthy subjects but not in heart transplanted patients. In our opinion, the increase of atrial natriuretic peptide is a counterregulatory mechanism aimed to compensate the cyclosporine-mediated activation of the renin-angiotensin-aldosterone system. The disappearance of the plasma renin activity, aldosterone and atrial natriuretic peptide circadian rhythm can be ascribed to the constant activation of the renin-angiotensin-aldosterone system. The hypocortisolism is due, in our opinion, both to glucocorticoid therapy and increase of plasma ANP concentration.

Circadian rhythm of blood pressure and heart rate in cardiopathic patients before and after heart transplantation.

The aim of this study was to investigate the natural history of the circadian rhythm of blood pressure (BP) and heart rate (HR) in 10 patients with heart failure (class IV of the New York Heart Association), who underwent heart transplantation because of primary congestive cardiomyopathy. The control group was 10 age-matched clinically healthy subjects. The BP and HR monitorings were performed before and after transplantation. Preoperatively, analysis of variance and cosinor methods validated the occurrence of a statistically significant BP and HR circadian rhythm in cardiopathic patients. Over the 4 days after surgery, both the cosinor method and serial section analysis were unable to validate a 24-h periodicity for BP and HR in patients with heart transplants. Six months after surgery, the BP and HR circadian rhythm was not detected as well. One year after transplantation, the BP and HR circadian rhythm was statistically validated. The recovery of the BP and HR circadian rhythm 1 year after heart transplantation can be regarded as a clinical sign of a reacquired susceptibility to neurovegetative chronoregulation.

Surgical treatment of an asymmetric double monstrosity with esophageal atresia, omphalocele, and interventricular defect.

In June 1981, at the Department of Pediatric Surgery, Children's Hospital, Palermo, we successfully operated on a male infant born with a set of accessory lower limbs attached to the sternum, a type IV esophageal atresia, omphalocele, and an interventricular defect (VSD).

Atrial natriuretic peptide in normotensive and hypertensive heart transplanted patients.

AIM OF THE STUDY: The present study is aimed to investigate the 24-hour pattern of Atrial Natriuretic Peptide (ANP) plasma concentration in normotensive (N) and hypertensive (H) heart transplanted patients (HTP) in order to detect the pathophysiological role of blood pressure regimen for ANP increase in HTP. METHODS: Eight NHTP and five HHTP have been investigated, all being hemodynamically compensated, without histological evidence of rejection and treated by Cyclosporine, Azathioprine and Prednisone. The control group was constituted by 10 clinically healthy subjects (CHS). ANP was assayed six times over the 24 h span. The contrasts between groups were statistically analyzed by means of Student's t-test for the 24 h mean values. RESULTS: The t-test found a statistically significant difference between the ANP 24 h mean levels either of CHS and HTP or NHTP and HHTP. The ANP 24 h mean plasma levels are increased of 190.4% in HHTP and of 44.3% in NHTP in comparison with CHS. DISCUSSION: The findings suggest that the further elevation of ANP in HHTP is a compensatory mechanism to antagonize high blood pressure. Moreover, being the ANP percent increase in HHTP three times more.

Piver's radical hysterectomy (type III): Endo-Gia 30 stapler versus traditional forcipressure for resection of the cardinal ligament.

OBJECTIVE: Morbidity and costs associated with Piver's radical hysterectomy (type III) are noteworthy. The Endo-Gia stapler method for resection of cardinal ligaments can reduce duration of surgery and hospitalization, blood loss, costs and postoperative infection rates. METHOD: Two groups of patients (homogeneous for age, weight and medical condition) were studied: one group was operated on using the Endo-Gia stapler method (n=52) and the other with the traditional forcipressure (n=13). The size of parametrial tissue removed, blood loss, duration of surgery, duration of hospitalization, cost of materials and postoperative fever were compared in the two groups. RESULT: Mean operative times were lower in the Endo-Stapler group than in the controls (mean 180 min versus 220 min). Mean blood loss was 300 cc in the stapler group versus 450 cc in the forcipressure group. Mean cost of surgery (considering costs of materials, hospital stay. duration of surgery), was lower in the stapler group (3,095 euros) than in the group who underwent traditional surgery (3,434 euros). CONCLUSION: Our data suggest the Endo-Gia stapler method significantly reduces blood loss, operative time and cost.

Metabolic and cardiorespiratory responses to continuous box lifting and lowering in nonimpaired subjects.

STUDY DESIGN: A within-subject experimental design. OBJECTIVES: To compare the magnitude of metabolic and cardiorespiratory changes produced during box lifting and lowering among combinations of lift technique (leg lift and leg-torso lift) and lift weight (10.8 and 15.4 kg). BACKGROUND: Continuous box lifting and lowering can be used as an exercise in a low-back rehabilitation program. Awareness of the possible cardiovascular stress of this activity is important to the clinician because some patients may have existing cardiovascular pathologies or possess unknown risk factors for cardiovascular disease. METHODS AND MEASURES: A group of 17 nonimpaired men 26 +/- 8 years of age (mean +/- SD) performed the 4 experimental trials on different days in a counterbalanced order determined by a Latin Square design. Lifting and lowering was performed for 6 continuous minutes at a rate of 12 cycles per minute. Physiologic variables were oxygen uptake, minute ventilation, heart rate, systolic blood pressure, diastolic blood pressure, metabolic equivalent, and rate-pressure product. RESULTS: There were stepwise increases in the values for oxygen uptake, minute ventilation, heart rate, metabolic equivalent, and rate-pressure product from the leg-torso lift to the leg lift and from 10.8 to 15.4 kg of weight within each lift technique (with the exception that minute ventilation and heart rate did not differ between the leg-torso lift at 15.4 kg and the leg lift at 10.8 kg). For the 4 lifts, values (mean +/- SD) varied from 20.3 +/- 5.4 to 28.8 +/- 5.8 mL x kg x min(-1) for oxygen uptake, 42.2 +/- 11.1 to 66.4 +/- 15.2 L x min(-2) for minute ventilation,129 +/- 20.6 to 156 +/- 16.5 beats x min(-1) for heart rate, 5.8 +/- 1.6 to 8.2 +/- 1.6 for metabolic equivalent, and 197 +/- 49.4 to 245 +/- 41.2 for rate-pressure product (x10(-2)). CONCLUSION: The leg lift with the 15.4-kg weight produced the greatest physiologic stress. Because of the magnitude of the increase in the variables measured for all 4 types of lifts, clinicians should closely monitor patients' response to this type of exercise.

Herpes simplex pneumonia in a heart transplant recipient.

An unusual case of Herpes simplex virus (HSV) pneumonia in a heart transplant recipient receiving chronic immunosuppressive therapy is reported. This infection presented an indolent course manifested by a chronic left pulmonary infiltrate unresponsive to antibiotic therapy and mild hypoxemia. Death eventually occurred as a consequence of an other infectious complication of the postoperative period. The HSV etiology of the necrotizing pneumonia observed at autopsy was established on the basis of histologic findings.