Sentinel lymph node (SLN) isolated tumor cells (ITCs) in otherwise stage I/II endometrioid endometrial cancer: To treat or not to treat?

OBJECTIVES: To assess associations between treatment and recurrence-free survival (RFS) among patients with isolated tumor cells (ITCs) in sentinel lymph nodes (SLN) and otherwise stage I/II endometrioid endometrial cancer (EC). METHODS: A multi-institutional retrospective study of patients with SLN ITCs (<200 cells and < 0.2 mm) was performed. Only patients with otherwise stage I/II EC, endometrioid histology, and no evidence of micro-or macrometastases were included. Univariate and multivariable Cox proportional hazard models were used to evaluate associations between treatment, tumor characteristics, and RFS. RESULTS: 175 patients were included. Median follow up time was 31 months. 39% stage IB and 12% stage II disease. 76 (43%) received no adjuvant therapy or vaginal brachytherapy only (NAT/VBT), 21 (12%) had external beam radiation (EBRT), and 78 (45%) received chemotherapy +/- radiation. Patients who received chemotherapy more often had tumors with deep myoinvasion, lymphovascular space invasion (LVSI), and higher grade. Nine (5.1%) patients recurred; 5 distant, 3 retroperitoneal, and 1 vaginal. Extra-vaginal recurrences were similar in patients with or without chemotherapy (5.2% vs 3.8%, p = 0.68). After controlling for stage, LVSI and grade, chemotherapy and EBRT were not associated with RFS (HR = 0.63, 95%CI 0.11-3.52, and HR = 0.90, 95%CI 0.22-3.61, respectively). Type of lymph node dissection and ITC detection method were not associated with RFS. CONCLUSIONS: Risk of retroperitoneal and/or distant recurrence is low (4.6%) for patients with stage I/II endometrioid EC and ITCs in SLNs regardless of treatment. Our preliminary data suggests that adjuvant therapy may not be significantly associated with RFS. However, longer follow-up time and a larger sample size are needed before definitive recommendations regarding adjuvant therapy for patients with EC and only ITCs in SLN can be made.

Repeat discectomy for recurrent same level disc herniation: A literature review of the past 5 years.

Background: Recurrent disc herniations remain a challenge in spinal surgery. Although some authors recommend a repeat discectomy, others offer more invasive secondary fusions. Here, we reviewed the literature (2017-2022) regarding the safety/efficacy of treating recurrent disc herniations with repeated discectomy alone. Methods: Our literature search of recurrent lumbar disc herniations included; Medline, PubMed, Google scholar, and the Cochrane database. We focused on the types of discectomy performed, perioperative morbidity, costs, length of surgery, pain scores, and incidence of secondary dural tears. Results: We identified 769 cases that included 126 microdiscectomies, and 643 endoscopic discectomies. Rates of disc recurrence ranged from 1% to 25% with accompanying secondary durotomy varying from 2% to 15%. In addition, operative times were relatively short, ranging from 29.2 min to 125 min, with a relatively small average estimated blood loss (i.e., minimal to maximally 150 mls). Conclusion: Repeated discectomy was the most commonly performed treatment for same-level recurrent disc herniations. Despite minimal intraoperative blood loss and short operating times, there was a significant risk of durotomy. Notably, patients must be informed that more extensive bone removal for treating recurrent disc increases the risk for instability warranting subsequent fusion.

Dural arteriovenous fistula of the torcular herophili presenting with hydrocephalus and venous congestion in an 8-month-old child: A case report.

Dural arteriovenous fistulas (DAVFs) are direct communication between the dural arterial and venous systems. They are more common in adults. In children, they are relatively rare. Hydrocephalus is a common problem in pediatrics with a variety of causes. However, very few cases of hydrocephalus as a complication of DAVF have been reported in the literature. This case describes an 8-month-old male child with a large DAVF at the torcular herophili who presented with regression of milestones and hydrocephalus. Magnetic resonance imaging (MRI) on admission showed triventricular hydrocephalus and a massively dilated torcular with a compressed fourth ventricle. Angiography confirmed the presence of a DAVF at the torcula with arterial feeders from the posterior circulation. Endovascular embolization was performed with >80% embolization of the fistula with no complications. Control MRI immediately postoperative was acceptable. No cerebrospinal fluid (CSF) diversion was performed. At a 3-month follow-up, the child had attained all developmental milestones for age. MRI showed normal CSF dynamics and a further reduction in the size of the torcula. Despite being rare, DAVFs should be considered as a possible cause of pediatric hydrocephalus, and treating them can lead to a resolution of the mechanisms inducing hydrocephalus. CSF shunting should be reserved for those cases with persistent hydrocephalus and raised intracranial pressure despite endovascular treatment.

Inhibition of primary ADP-induced platelet aggregation in normal subjects after administration of nitrofurantoin (furadantin).

The evidence indicating that platelets may play a role in the occurrence of certain thromboembolic phenomena has stimulated a search for inhibitors of platelet function. This report presents data to indicate that nitrofurantoin is a potent inhibitor of primary ADP-induced platelet aggregation. The addition of 10 muM nitrofurantoin to citrated platelet-rich plasma obtained from 12 normal subjects produced a 29+/-6% (2 SD) inhibition of the velocity of platelet aggregation induced by 2 muM ADP. The inhibitory effect of nitrofurantoin demonstrated competitive kinetics in respect to ADP. The intravenous (180 mg) or oral (200 mg) administration of nitrofurantoin produced a serum nitrofurantoin concentration ranging from 2.7 to 23 muM in 28 normal subjects. Platelet-rich plasma obtained from these subjects demonstrated inhibition of the velocity of ADP-induced platelet aggregation that correlated with the log of the serum nitrofurantoin concentration (P < 0.001). Collagen-induced platelet aggregation was also inhibited in a dose-related manner, and the bleeding time was significantly prolonged in the two subjects with the highest serum nitrofurantoin concentration. These studies indicate that nitrofurantoin in vivo inhibits platelet function to a degree that is proportional to the serum nitrofurantoin concentration.

Serum prostacyclin binding defects in thrombotic thrombocytopenic purpura.

To understand the pathophysiologic significance of abnormal serum prostacyclin (PGI2) binding activities in thrombotic thrombocytopenic purpura (TTP), we evaluated the PGI2 binding characteristics in three chronic TTP sera and 19 normal sera. PGI2 binding by serum was rapid and reversible. The binding activity in TTP sera (22.1 +/- SD, 4.4%) was significantly lower than that of normal sera (42.2 +/- 6.2%). Moreover, the antiaggregating activity and 6-keto-prostaglandin F1 alpha (6KPGF1 alpha) content in the gel filtrates representing the binding peak was proportionally lower in a TTP serum than normal serum. Although normal and TTP sera bound [14C]arachidonate with similar activity, and neither bound [3H]6KPGF1 alpha, there was a difference in prostaglandin E1 (PGE1) binding. Binding of [3H]PGE1 was subnormal in two TTP sera (W.J. and T.G.) and normal in the third (H.S.). Normal serum corrected the binding defects of TTP serum. Interestingly, the mixture of two TTP sera (W.J. and H.S.) mutually corrected their PGI2 binding defects. In addition, although in vivo plasma transfusions improved the PGI2 binding activity of W.J. and H.S., there existed a striking difference in the nature of their response. These observations indicate that there is at least two types of PGI2 binding defects in TTP. Our data indicate that TTP is associated with diminished serum binding of PGI2. This defect may reduce the availability of PGI2 to damaged vascular sites and decrease an important modulator of platelet thrombus formation at times of severe vascular insult.

Functional distinction between serotonin uptake and serotonin-induced shape change receptors in rat platelets.

Tyramine and dopamine are taken up by rat platelets through the serotonin uptake mechanism while phenethylamine is not taken up. This indicates that an aromatic hydroxyl group is a structural requirement for the uptake of phenethylamine derivatives by rat platelets. Although none of these phenethylamine derivatives induce platelet shape change, they inhibit serotonin-induced shape change and serotonin uptake with the same relative potency (tyramine greater than phenethylamine greater than or equal to dopamine). This suggests that the receptors controlling serotonin uptake and serotonin-induced shape change have a common structural component that binds phenethylamine derivatives. However, the fact that phenethylamine derivatives activate the serotonin uptake mechanism but do not induce platelet shape change suggests that serotonin uptake and serotonin-induced shape change are mediated by two distinct activation sites of serotonin receptors.

The treatment of the hemolytic-uremic syndrome with inhibitors of platelet function.

In four patients with clinical and laboratory manifestations of the hemolytic-uremic syndrome, the administration of aspirin and dipyridamole was associated with a dramatic and rapid increase in the platelet count. In three of the four patients there was also improvement in neurologic or renal function. No subject experienced bleeding or other untoward effects. We conclude that a trial of aspirin and dipyridamole therapy is warranted early in the course of the hemolytic-uremic syndrome.

Kinetic parameters of platelet aggregation as an expression of platelet responsiveness.

The kinetics of platelet aggregation induced by collagen and by ADP were studied. The maximum aggregation (deltaLTmax) and the ADP and collagen concentrations required to produce half-maximum aggregation (Kd) were determined using platelets obtained from normal individuals, individuals who ingested aspirin and individuals whose platelet-rich plasma (PRP) demonstrated spontaneous aggregation. The Kd and deltaLTmax for ADP-induced platelet aggregation were variable and markedly affected by the citrate concentration. Conversely, kinetic parameters of collagen-induced aggregation were more reproducible and less affected by citrate. The Kd for collagen in platelet aggregation was increased following aspirin ingestion and decreased in samples of PRP that demonstrated spontaneous aggregation. These results suggest that kinetic parameters of platelet aggregation may be useful to express the responsiveness of platelets.

Platelet monoamine oxidase and epinephrine-induced platelet aggregation.

Platelet MAO activity and the aggregation response to epinephrine, ADP, and collagen were measured in normal subjects. There was a direct correlation between the amount of platelet MAO activity and the per cent aggregation induced by 1 and 2 micrometer epinephrine. There were lesser correlations between platelet MAO and ADP or collagen-induced aggregation. These findings suggest that platelet MAO may play a role in determining the response of human platelets to epinephrine.

Red cell transfusion therapy in chronic anemia.

This article discusses anemia, the evaluation of symptoms, and the compensatory mechanisms that are brought into play by chronic anemia. The oxygen dissociation curve is described as is the effect of 2,3-DPG on hemoglobin-oxygen binding. Human tolerance to anemia is discussed and the article concludes with proposed transfusion strategies in chronic anemia.

THe beta-Blocker Heart Attack Trial: studies of platelets and factor VIII.

Serial studies of platelets and factor VIII were performed in 16 patients enrolled in the Beta Blocker Heart Attack Trial. Eight patients received placebo, and eight were treated with propranolol, in doses ranging from 40 to 320 mg per day for periods of from 6 to 31 months. No differences in platelet-collagen affinity, factor VIII coagulant activity, factor VIII related antigen, or ristocetin cofactor activity were observed between treated and untreated patients. However, circulating platelet aggregates, which were initially increased in both groups, significantly declined in those receiving propranolol (p less than 0.05). This indicates that customarily used doses of propranolol affect platelet reactivity in vivo.

Abnormalities in platelet function and morphology in a case of thrombocythemia.

A patient with "life-long" bleeding problems and thrombocythemia had normal results on routine coagulation and fibrinolysis tests, but platelet function tests, including bleeding time, platelet adhesiveness, aggregation, and uptake and release of labeled serotonin were markedly altered. In addition, several types of ultrastructural abnormalities not reported previously were observed in some of the patient's platelets. The relationship between thrombocythemia, platelet dysfunction, and abnormal morphology is discussed.

Platelets and the hemolytic-uremic syndrome.

Clinical studies suggest that the microthrombi characteristically found in hemolytic-uremic syndrome (HUS) may be the consequence of an uncontrolled platelet-endothelial interaction. A defect in prostacyclin production which is corrected by normal plasma may be the fundamental pathogenic mechanism. For this reason, efforts should be made to confirm the recent case reports which suggest that plasma infusion or exchange may be more effective than hemostatic inhibitors in the achievement of clinical remission in HUS.

Case report: mixed-field agglutination in a patient with a weak D antigen presenting as a possible fetal-maternal hemorrhage.

A gravida 1, para O, 17-year-old black female was found on prenatal testing to be group O, Du+, the latter test showing many unagglutinated cells. Because of the mixed-field appearance, the patient was thought initially to have bad a fetal-maternal hemorrhage. Additional red cell typings were performed, but no other apparent mixed-field reactions were observed. The Kleihauer- Betke test and hemoglobin electrophoresis indicated that the mixed-field agglutination was not due to a fetal-maternal hemorrhage. Thus, the finding of a mixed-field D typing could he explained best by a weak D antigen.