Is Substantial Lymphovascular Space Invasion Prognostic for Clinical Outcomes in Type II Endometrial Cancer?

AIMS: Substantial lymphovascular space invasion (LVSI) compared with none or focal LVSI is predictive of lymph node involvement and worse clinical outcomes in endometrioid-type endometrial carcinoma. We aimed to quantify the incidence of substantial LVSI in type II (clear cell and serous) endometrial cancer and correlate the extent of LVSI with clinical outcomes. MATERIALS AND METHODS: A retrospective review was conducted on type II endometrial cancer patients who underwent surgical management from July 2017 to December 2019 using the three-tier LVSI scoring system. Binary logistic regression and Cox regression were used to analyse predictors of lymph node involvement or survival outcomes, respectively. The Kaplan-Meier method and Log-rank test were used to analyse differences in locoregional disease-free survival (LR-DFS), distant metastasis disease-free survival (DM-DFS) and overall survival between patients with substantial versus none/focal LVSI. RESULTS: In 79 patients with type II endometrial carcinoma, no LVSI, focal LVSI and substantial LVSI was present in 48.1%, 15.2% and 36.7% of patients, respectively. Lymph nodes were involved in 0.0% with no LVSI, 20.0% with focal LVSI and 60.0% with substantial LVSI (P < 0.001). The median follow-up was 22.2 months. In patients with none/focal versus substantial LVSI, the 2-year LR-DFS and DM-DFS rates were 91.5% versus 71.4% (P = 0.01) and 90.2% versus 63.8% (P = 0.005), respectively. On univariate analysis, myometrial invasion ≥50%, tumour size ≥3.6 cm, substantial versus none/focal LVSI, lymph node involvement and omission of adjuvant radiotherapy were significant predictors for worse LR-DFS and DM-DFS (P < 0.05). DISCUSSION: Substantial LVSI has a high incidence in type II pathology at our institution and predicts for lymph node involvement and worse clinical outcomes.

Emergence of Porcine Circovirus 2 Associated Reproductive Failure in Southern India.

Incidence of unusually high numbers of stillbirths was observed at a piggery unit at the Veterinary University research farm in Tamil Nadu State of India. Systematic examination of the tissue from stillborn piglets led to the identification of presence of Porcine circovirus 2 (PCV2). Detailed analysis utilizing electron microscopy, polymerase chain reaction and sequencing confirmed the presence of PCV2 in the tissue of affected piglets. Histopathology analysis of the affected piglet tissue showed lymphoid cell depletion of lymphnodes, spleen and infiltration of liver, kidney, myocardium, etc. Retrospective examination of the morbidity and mortality history in the farm revealed high mortality in young and weanling piglets suggestive of PCV2 infection-induced diseases. This is the first report of emergence of major disease incidence in farmed swine due to PCV2 infection in India.

Symptomatic aneurysm of ductus arteriosus in neonates.

Four neonates presented within 24 hours of birth with stridor, respiratory distress and a weak cry. Clinical examination of the cardiovascular system revealed no abnormality. The transthoracic echocardiogram showed large aneurysm of ductus arteriosus at the aortic isthmus, tapering to a small tortuous channel at the site of pulmonary artery insertion. Computerized tomography scan performed in two of the neonates demonstrated considerable compression of adjacent thoracic structures. One required surgical excision due to persistence of symptoms. Serial echocardiograms in the remaining three babies showed transition through various stages of resolution over a period of 6 weeks to 3 months, resulting in the obliteration of the aneurysm. All babies are doing well during the follow-up.

Substrate based ablation of ventricular tachycardia through an epicardial approach.

Ventricular tachycardia (VT) occurring late after myocardial infarction is often due to reentry circuit in the peri-infarct zone. The circuit is usually located in the sub-endocardium, though subepicardial substrates are known. Activation mapping during VT to identify target regions for ablation can be difficult if VT is non inducible or poorly tolerated. In the latter, a substrate based approach of mapping during sinus rhythm in conjunction with pace mapping helps to define the reentry circuit and select target sites for ablation in majority of patients with hemodynamically unstable VT. Percutaneous epicardial catheter ablation has been attempted as an approach where ablation by a conventional endocardial access has been unsuccessful. We report a case of post myocardial infarction scar VT which could be successfully ablated with a substrate based approach from the epicardial aspect.

Successful catheter ablation of persistent electrical storm late post myocardial infarction by targeting purkinje arborization triggers.

Drug refractory ventricular tachycardia (VT) occurring as a storm after acute myocardial infarction has grave prognosis. We report a case of a middle-aged lady who presented with drug refractory VT that lead to persistent electrical storm two weeks after an anterior wall myocardial infarction. She underwent a successful catheter ablation of VT followed a few days later by implantation of an AICD. Catheter ablation of the VT could control the persistent electrical storm and the patient was free from a recurrence of VT at three month follow up.

Catheter ablation of fascicular ventricular tachycardia.

Fascicular ventricular tachycardia (VT) is an idiopathic VT with right bundle branch block morphology and left-axis deviation occuring predominantly in young males. Fascicular tachycardia has been classified into three subtypes namely, left posterior fascicular VT, left anterior fascicular VT and upper septal fascicular VT. The mechanism of this tachycardia is believed to be localized reentry close to the fascicle of the left bundle branch. The reentrant circuit is composed of a verapamil sensitive zone, activated antegradely during tachycardia and the fast conduction Purkinje fibers activated retrogradely during tachycardia recorded as the pre Purkinje and the Purkinje potentials respectively. Catheter ablation is the preferred choice of therapy in patients with fascicular VT. Ablation is carried out during tachycardia, using conventional mapping techniques in majority of the patients, while three dimensional mapping and sinus rhythm ablation is reserved for patients with nonmappable tachycardia.

Role of context in the relationship between form and function: structural plasticity of some PROSITE patterns.

True positive hits of PROSITE sequence pattern are expected to have a characteristic three-dimensional structure. The combined sequence-structure attributes of PROSITE patterns can be used for function prediction of an uncharacterized protein with known primary and 3D structure, a situation that might arise in structural genomics projects. We have found specific examples of true hits of PROSITE patterns displaying structural plasticity by assuming significantly different local conformation, depending upon the context. Our work highlights the importance of taking into account all the known distinct conformations of PROSITE patterns, while creating a sensitive 3D template for the pattern, for use in functional annotation.

Absent coronary venous sinus: a rare anomaly.

A 42-year-old man, presenting with dyspnea on exertion and ST segment depression on treadmill test, was found to have absent coronary venous sinus on coronary angiography. We report this case of isolated congenital absence of coronary venous sinus because of its rarity.

Transforming activity of EWS/FLI is not strictly dependent upon DNA-binding activity.

In approximately 85% of Ewing sarcomas, chromosomal translocations give rise to the chimeric gene EWS/FLI, encoding the N-terminus of the RNA binding protein EWS fused to the DNA-binding domain of the ETS protein FLI-1. EWS/FLI is a stronger transcriptional activator than wild-type FLI-1, although both proteins bind to the same DNA sequences in vitro. In addition, EWS/FLI, but not FLI-1, is a transforming oncogene in NIH3T3 fibroblasts. EWS/FLI is thought to transform through its ability to deregulate the expression of target genes. We introduced several point mutations into the ETS domain of EWS/FLI that abolished DNA-binding activity. Although two of these mutations disrupted the transforming activity of EWS/FLI, one mutated protein containing a substitution of isoleucine 347 with glutamic acid (I347E) retained diminished transforming activity. In addition, EWS/FLI I347E did not activate expression of the endogenous EWS/FLI target gene manic fringe (MFNG). These studies demonstrate that a portion of the oncogenic activity of EWS/FLI is independent of FLI DNA-binding activity.

Safety of thrombolytic therapy following acute myocardial infarction in patients above 65 years.

The safety of thrombolytic therapy for acute myocardial infarction in the elderly population has not been clearly established. In a retrospective study we evaluated the efficacy and complications of thrombolytic therapy in the elderly as compared to younger patients. Consecutive 588 patients who received thrombolytic therapy were studied. Clinical data in 136 patients aged above 65 years were compared with 85 patients below 40 years. Cigarette smoking was a common risk factor in the young (46 vs 13; p < 0.0001). Coexistent systemic diseases and conduction system disturbances (28 vs 9; p < 0.05) were common in the older patients, but the incidence of bleeding complications to thrombolytic therapy (6 vs 1; p = NS) was not found to be higher. Ninety percent of the elderly who had cardiogenic shock died. There was no significant difference between the two groups in reinfarction rate (12 vs 15; p = NS) and post-infarct angina (20 vs 20; p = NS). Coronary angiography revealed a higher incidence of multivessel disease in the elderly. To conclude, thrombolytic therapy is safe and effective even in older individuals.

Semi-quantitative planar scintigraphy using thallium 201 for detection and localization of coronary artery disease: correlation with coronary angiography.

Thallium 201 exercise redistribution planar myocardial perfusion scan using semiquantitative technique was performed in 80 symptomatic patients undergoing coronary angiography. Out of the 240 vessels studied by angiography, more than 70% luminal narrowing was detected in 87 vessels, borderline stenosis was found in 49 arteries and the remaining 104 vessels were normal. Thallium scan correctly identified the significant stenosis in 76 vessels and the absence of stenosis in 102 vessels. In addition, perfusion abnormality was found in relation with 21 vessels of borderline stenosis. The sensitivity and specificity of Thallium scan were estimated as 92% and 95% for left anterior descending artery (LAD), 79% and 98% for left circumflex artery (LCX), 88% and 100% for right coronary artery (RCA) and 87% and 98% for all coronary arteries combined together (ACA).

Morphometric analysis of coronary lesions in patients with unstable angina--an arteriographic study.

In 100 patients with unstable angina and 50 patients with stable angina qualitative morphology of coronary artery lesions were compared by angiography. The mean age of the patients was 51 years. In the unstable angina group, 50 patients had rest angina, 32 had crescendo angina and 18 had denovo angina; 31 patients had single vessel disease, 33 had two vessel disease, 34 had triple vessel disease and 2 had left main disease. 'Angina-producing' artery could be identified in 90 out of 100 patients. Ten totally occluded vessels were excluded from analysis. Lesions causing diameter stenosis of greater than 50% could be categorised to one of the following groups: a) Concentric stenosis (18 vessels), b) Type I eccentric lesion (asymmetric narrowing with smooth borders and broad neck--20 vessels), c) Type II eccentric lesion (asymmetric narrowing with narrow neck and overhanging irregular edges--47 vessels), and d) Multiple irregularities (15 vessels). Lesions in 9 vessels showed an associated thrombus. It appears that Type II eccentric lesions are frequent in patients with unstable angina; they probably represent ruptured atherosclerotic plaque or partially occlusive thrombi or both.

Differential effects of autonomic blockade on sinus and atrioventricular nodal function in normals and in intrinsic sinus node dysfunction.

The effect of pharmacologic total autonomic blockade on sinus and atrioventricular nodes was studied in 10 normals and 21 patients with sick sinus syndrome with abnormal intrinsic corrected sinus node recovery time. In normals the intrinsic heart rate (113.3 +/- 11.6 beats/min) was higher than the resting heart rate (87.3 +/- 12 beats/min; P less than 0.001). The AH interval at an identical paced rate decreased from 119 +/- 36 msec to 93 +/- 17.6 msec after autonomic blockade (P less than 0.05). Mean atrial paced cycle length at AH Wenckebach block was not different during control and after drugs (319 +/- 46 msec vs. 311.5 +/- 39 msec; P = NS). Although sinus cycle length shortened in all cases after autonomic blockade, paced cycle length at AH Wenckebach increased (4) or remained unchanged (3) in 7 cases. Maximum normal "intrinsic" paced cycle length at AH Wenckebach was 390 msec (mean +/- 2 SD). In sick sinus syndrome, resting heart rate (66.3 +/- 18.8 beats/min) and intrinsic heart rate (74.6 +/- 16.4 beats/min) were similar (P = NS); AH at identical paced rate: control 136.6 +/- 54 msec, after drugs 130.5 +/- 35 msec (P = NS); cycle length at AH Wenckebach: control 380.5 +/- 73 msec, after autonomic blockade 383 +/- 49 msec (P = NS). Two of 3 cases with abnormal atrioventricular nodal response to atrial pacing during control normalized after autonomic blockade; 9/21 (42.8%) cases developed AH Wenckebach at cycle length greater than 390 msec after autonomic blockade. The data suggest that the autonomic nervous system has differential effects on sinus and atrioventricular nodes. Patients with sick sinus syndrome frequently have abnormalities of "intrinsic" atrioventricular nodal conduction unmasked by autonomic blockade.