Double chambered left ventricle-institutional experience of two cases.

BACKGROUND: Double Chambered Left Ventricle is a very rare congenital cardiac condition with limited cases reported in literature, etiology of which is obscure and presentation can be varied. AIM OF THE STUDY: To share our experience of two diverse cases of Double Chambered Left Ventricle at our institute. RESULTS: Two diverse cases of Double Chambered Left Ventricle were appropriately diagnosed and successfully managed. One of which one was congenital and the other was acquired METHODS: Both the patients had an uneventful peri-operative period. CONCLUSIONS: Double Chambered Left Ventricle is a condition which remains an enigma. Diagnosis requires a high degree of radiological suspicion for prompt diagnosis and good surgical outcomes.

Right pulmonary artery-Left atrium fistula: An institutional experience of seven cases over two decades.

BACKGROUND: We report a series of 7 patients of right pulmonary artery to left atrium fistula operated in our institute between 1998 and 2019. AIM OF THE STUDY: To present a comprehensive management of right pulmonary artery to left atrium fistula in an organised manner with excellent results, even in adult population. METHODS: Seven consecutive patients of RPA to LA fistula were investigated with appropriate diagnostic modalities and underwent successful surgical correction. RESULTS: Post procedure the oxygen saturation improved to >95% in all the patients. There were no early or late post-operative deaths. All patients underwent TTE at every follow up. CONCLUSION: Appropriate use of imaging techniques helps in exact diagnosis with anatomical delineation which decides the further line of management in relieving the symptoms and prevention of complications of the fistula.

Sinus of valsalva aneurysm: A single institutional experience with 216 patients over 30 years.

BACKGROUND: Sinus of valsalva aneurysm (SVA) with rupture is a rare cardiac anomaly which can be congenital or acquired with reported incidence of 0.46%-3.57% among Asians population. AIM OF THE STUDY: The aim of this study is to analyze 30 years of single institutional surgical experience in management of 216 cases with SVAs from 1992 till date. METHODS: Age group was from 6 to 64 years (mean: 32.5 ± 11 years) with male to female ratio of 2.2:1. The aneurysms originated from right coronary sinus in 181 cases (83.79%), noncoronary sinus in 35 cases (15.74%) and ruptured into the right ventricle in 149 cases (68.98%), right atrium in 59 cases (27.31%). Bicameral approach was used in majority of the cases (n = 213, 98.61%). Aneurysms were repaired using Dacron patch in 173 cases (80.09%) and direct closure in 43 cases (19.9%). Associated ventricular septal defect was closed with Dacron patch in 123 cases (56.94%). Aortic valve was replaced in 21 cases (9.72%) and aortic valve repair was performed in 14 cases (6.48%) for associated Aortic regurgitation. RESULTS: There were no perioperative hospital deaths. Follow-up was available in 204 patients (94.44%) ranging from 2 to 26 years (mean: 10 ± 5.6 years). Two deaths (0.92%) occurred during the postoperative follow-up period. The actual survival was 99.5% at 1 year, 99% at 5 and 10 years. CONCLUSION: Long term results of surgically repaired SVAs are good with low morbidity (3.24%) and mortality (0.92%) even when associated with major cardiac anomalies. Aortic valve repair and replacement both are equally feasible alternatives for management of moderate to severe aortic regurgitation with associated merits and demerits.

Germline genetic testing in breast cancer: Rationale for the testing of all women diagnosed by the age of 60 years and for risk-based testing of those older than 60 years.

Approximately 5% to 10% of women diagnosed with breast cancer will have a pathogenic variant (PV) in a hereditary cancer susceptibility gene, and this has significant implications for the management of these patients and their relatives. Despite the benefits of genetic testing, many eligible patients with breast cancer never undergo testing because of various barriers, including complicated testing criteria such as those from the National Comprehensive Cancer Network (NCCN). In 2019, the American Society of Breast Surgeons (ASBrS) proposed germline genetic testing for all patients with breast cancer to increase the identification of PV carriers. In 2020, a Mayo Clinic study highlighted the limitations of these 2 genetic testing guidelines (NCCN and ASBrS) and proposed a hybrid approach of testing all women diagnosed with breast cancer by the age of 65 years and using NCCN criteria for older patients. This commentary presents an updated analysis of the Mayo Clinic data and discusses the rationale for using the age of 60 years rather than 65 years as the cutoff for this hybrid approach. Using an age at diagnosis of ≤60 or ≤65 years for the universal testing of patients with breast cancer detected more PVs (11.9% [16 of 134] and 15.7% [21 of 134], respectively) in comparison with using the NCCN criteria. Lowering the age for universal testing from 65 to 60 years maintained the sensitivity of detecting a PV at >90% while sparing testing for an additional 10% of women. Compared with the testing of all patients, the hybrid approach would allow 31% of all women with breast cancer to forgo testing and result in fewer variants of uncertain significance identified and, therefore, would decrease the chance of harm from misinterpretation of these variants.

Medical Management of newly diagnosed breast cancer in a BRCA1/2 mutation carrier.

Germline BRCA1/2 mutations may be infrequent in unselected breast cancer population but are concentrated in those with triple-negative breast cancer or high-risk family history. Insight into the biology of BRCA mutation is now allowing a targeted therapeutic approach to these carriers with breast cancer. Functional BRCA genes play a critical role in DNA damage repair. Agents such as platinum salts and poly (ADP-ribose) polymerase (PARP) inhibitors exploit this vulnerability of impaired DNA damage repair mechanism in BRCA mutant cancers to leverage therapeutic benefit. Research has demonstrated improved response rates to platinum salts in BRCA-mutated compared with non-BRCA-mutated breast cancer, particularly in the metastatic setting. Additionally, clinical trials of single-agent PARP inhibitors have shown encouraging response rates and progression-free survival in patients with BRCA1/2-mutated breast cancer. In this review, we summarize the medical management of BRCA-associated breast cancer.

Intrinsic molecular subtypes of breast cancers categorized as HER2-positive using an alternative chromosome 17 probe assay.

The 2013 update of the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) human epidermal growth factor receptor 2 (HER2) testing guidelines recommend using an alternative chromosome 17 probe assay to resolve HER2 results determined to be equivocal by immunohistochemistry (IHC) or fluorescence in-situ hybridization (FISH). However, it is unclear if cases considered HER2-positive (HER2+) by the alternative probe method are similar to those classified as HER2+ by traditional IHC and FISH criteria and benefit the same from HER2-targeted therapies. We studied the clinical and pathologic features of all 31 breast cancers classified as HER2+ by the alternative probe method at our institution since 2013 and determined their PAM50 intrinsic molecular subtypes. For comparison, we analyzed 19 consecutive cases that were classified as HER2+ by traditional FISH criteria during the same time period. Thirty (97%) cancers in the alternative probe cohort were estrogen receptor (ER)-positive (ER+), while only 9/19 (47%) of traditional HER2 controls were ER+ (p = 0.0002). Sufficient tissue for intrinsic subtype analysis was available for 20/31 cancers in the alternative probe cohort and 9/19 in the traditional HER2+ group. None (0%) of the 20 alternative probe-positive cases were of the HER2-enriched intrinsic subtype, while 8/9 (89%) of those HER2+ by traditional FISH criteria were HER2-enriched (p = 0.0001). These findings suggest that breast cancers classified as HER2+ only by the alternative probe method are biologically distinct from those classified as HER2+ by traditional criteria, and raises questions as to whether or not they derive the same benefit from HER2-targeted therapies.

Bicuspidization of the morphological tricuspid aortic valve with ascending aorta replacement in a 5-year-old child.

Ascending aortic aneurysms are rare in children and may lead to aortic insufficiency, dissection, and/or rupture. We present a 5-year-old child diagnosed with an ascending aortic aneurysm and severe aortic insufficiency, successfully treated with ascending aortic replacement with an aortic valve repair using a bicuspidation technique.

Crisscross heart-Morphology, clinical diagnosis, and management options.

Crisscross heart is a rare cardiac malformation characterized by crossing of the inflow streams of the two ventricles due to a twisting of the heart about its long axis. The developmental mechanisms and causes of crisscross heart remain unknown. Neonates present with cyanosis and a systolic murmur. In this study, we report a case of crisscross heart with situs inversus, concordant atrioventricular and ventriculo arterial connection with ventricular septal defect and pulmonary stenosis, and review the literature on this rare cardiac malformation.

Management of atrial thrombus formation following surgical closure of an atrial septal defect.

Acute thrombus formation on pericardial patches used to close atrial septal defects (ASDs) is uncommon. We present two patients with thrombus formation on native pericardial patches following ASD closure and discuss the management of this complication.

Use of Volatile Anesthetic Agent in Extracorporeal Circuit as a Cause of Break in Polycarbonate Connector-Lessons Learnt.

Mishaps, near misses, and lethal incidents are known to occur during cardiopulmonary bypass. We share one such rare case of break in polycarbonate connector because of the use of isoflurane in extracorporeal circuit and its successful management.

Accessory Tricuspid Valve Leaflet-Morphology, Diagnosis, and Management.

Accessory tricuspid valve tissue is a rare entity associated with congenital cardiac anomalies. We report a seven-month-old child who underwent ventricular septal defect closure with excision of an accessory tricuspid valve leaflet and discuss their morphology, clinical presentation, diagnostic modalities, and treatment options. doi: 10.1111/jocs.12731 (J Card Surg 2016;31:324-326).

Bif-1 haploinsufficiency promotes chromosomal instability and accelerates Myc-driven lymphomagenesis via suppression of mitophagy.

Malignant transformation by oncogenes requires additional genetic/epigenetic changes to overcome enhanced susceptibility to apoptosis. In the present study, we report that Bif-1 (Sh3glb1), a gene encoding a membrane curvature­driving endophilin protein, is a haploinsufficient tumor suppressor that plays a key role in the prevention of chromosomal instability and suppresses the acquisition of apoptosis resistance during Myc-driven lymphomagenesis. Although a large portion of Bif-1­deficient mice harboring an Eµ-Myc transgene displayed embryonic lethality, allelic loss of Bif-1 dramatically accelerated the onset of Myc-induced lymphoma. At the premalignant stage, hemizygous deletion of Bif-1 resulted in an increase in mitochondrial mass, accumulation of DNA damage, and up-regulation of the antiapoptotic protein Mcl-1. Consistently, allelic loss of Bif-1 suppressed the activation of caspase-3 in Myc-induced lymphoma cells. Moreover, we found that Bif-1 is indispensable for the autophagy-dependent clearance of damaged mitochondria (mitophagy), because loss of Bif-1 resulted in the accumulation of endoplasmic reticulum­associated immature autophagosomes and suppressed the maturation of autophagosomes. The results of the present study indicate that Bif-1 haploinsufficiency attenuates mitophagy and results in the promotion of chromosomal instability, which enables tumor cells to efficiently bypass the oncogenic/metabolic pressures for apoptosis. .

Targeted Therapies and the Evolving Standard of Care for Triple-Negative and Germline BRCA1/2-Mutated Breast Cancers in the High-Risk, Early-Stage Setting.

PURPOSE: Immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the treatment landscape of metastatic triple-negative breast cancer (TNBC). Trial results have demonstrated the clinical benefit of these targeted agents in the advanced TNBC setting and have led to their evaluation in the treatment of high-risk, early-stage TNBC and BRCA-mutated breast cancer. We provide a summary of the results that have led to the establishment of the ICI pembrolizumab and the PARP inhibitor olaparib as new standards of care. METHODS: Using PubMed, we searched for original articles published in English between 2017 and 2022. Search terms included triple-negative breast cancer, adjuvant, neoadjuvant, immunotherapy, and PARP inhibitors. RESULTS: Two targeted therapies have been approved by the US Food and Drug Administration for the treatment of TNBC and BRCA-mutated breast cancers in the high-risk, early-stage setting on the basis of clinical trial results demonstrating improved clinical outcomes. For high-risk, early-stage TNBC, pembrolizumab was approved as neoadjuvant therapy in combination with chemotherapy and as a single agent for continued treatment after surgery; this approval was based on results of the KEYNOTE-522 trial. Olaparib was approved for the adjuvant treatment of patients with high-risk, early-stage human epidermal growth factor receptor type 2 (HER2)-negative breast cancer with germline BRCA1/2 mutations who have been previously treated with neoadjuvant or adjuvant chemotherapy on the basis of the OlympiA trial results. CONCLUSION: Clinical trial results demonstrate the pronounced clinical benefits of pembrolizumab combined with chemotherapy for high-risk, early-stage TNBC and adjuvant olaparib for high-risk, early-stage HER2-negative BRCA1/2-mutated breast cancer.

Clinical Equivalence of Trubond® and Ethibond® Braided Polyester Sutures for Valvular Prosthesis Fixation During Aortic or Mitral Valve Replacement: A Single-Blind Randomized Controlled Trial.

Background Paravalvular leak (PVL) following valve replacement is a serious cardiovascular complication that increases morbidity and mortality. Valve replacement with the interrupted suture technique using polyester suture provides adequate tensile strength and reduces the probability of tissue reaction. This study compared the clinical equivalence of Trubond®(Healthium) and Ethibond® (Ethicon, Johnson & Johnson) braided polyester sutures for valvular prosthesis fixation using interrupted suturing, with respect to the proportion of subjects having PVL after aortic valve (AV) or mitral valve (MV) replacement. Methodology Patients undergoing AV/MV replacement were enrolled and randomized in this study. The primary endpoint of this prospective, multicentric, two-arm, randomized (1:1), parallel-group, single-blind study (December 2020-October 2022) was the presence of PVL in Trubond® (n = 40) and Ethibond® (n = 42) groups within 26 weeks of surgery. The secondary endpoints included event rate of all-cause mortality, cardiac death, stroke, myocardial infarction, re-hospitalization, re-intervention, wound infection, operative time, intraoperative suture parameters, postoperative hospital stay, time to resume normal activities and work, quality of life, patient satisfaction, and adverse events in both groups. Results Patients who underwent AV/MV replacement and were followed up until 26 weeks had no incidence of PVL or other postoperative complications. No requirement for readmission or re-intervention was noted in both groups. Intraoperative suture handling characteristics, operative time, and hospital stay were also comparable between the groups. With each follow-up, subjects in both groups exhibited improved postoperative functional abilities, quality of life, and health status. Conclusions Trubond® braided polyester suture is clinically equivalent to Ethibond® braided polyester suture. Trubond® suture is safe and effective for valvular prosthesis fixation in patients undergoing AV or MV replacement.

Retrospective Cohort Study on the Limitations of Direct-to-Consumer Genetic Screening in Hereditary Breast and Ovarian Cancer.

PURPOSE: Among cancer predisposition genes, most direct-to-consumer (DTC) genetic tests evaluate three Ashkenazi Jewish (AJ) founder mutations in BRCA1/2, which represent a small proportion of pathogenic or likely pathogenic variants (PLPV) in cancer predisposing genes. In this study, we investigate PLPV in BRCA1/2 and other cancer predisposition genes that are missed by testing only AJ founder BRCA1/2 mutations. METHODS: Individuals were referred to genetic testing for personal diagnoses of breast and/or ovarian cancer (clinical cohort) or were self-referred (nonindication-based cohort). There were 348,692 participants in the clinical cohort and 7,636 participants in the nonindication-based cohort. Both cohorts were analyzed for BRCA1/2 AJ founder mutations. Full sequence analysis was done for PLPV in BRCA1/2, CDH1, PALB2, PTEN, STK11, TP53, ATM, BARD1, BRIP1, CHEK2 (truncating variants), EPCAM, MLH1, MSH2/6, NF1, PMS2, RAD51C/D, and 22 other genes. RESULTS: BRCA1/2 AJ founder mutations accounted for 10.8% and 29.7% of BRCA1/2 PLPV in the clinical and nonindication-based cohorts, respectively. AJ founder mutations accounted for 89.9% of BRCA1/2 PLPV in those of full AJ descent, but only 69.6% of those of partial AJ descent. In total, 0.5% of all individuals had a BRCA1/2 AJ founder variant, while 7.7% had PLPV in a high-risk breast/ovarian cancer gene. For non-AJ individuals, limiting evaluation to the AJ founder BRCA1/2 mutations missed >90% of mutations in actionable cancer risk genes. Secondary analysis revealed a false-positive rate of 69% for PLPV outside of non-AJ BRCA 1/2 founder mutations. CONCLUSION: DTC genetic testing misses >90% of BRCA1/2 PLPV in individuals of non-AJ ancestry and about 10% of BRCA1/2 PLPV among AJ individuals. There is a high false-positivity rate for non-AJ BRCA 1/2 PLPV with DTC genetic testing.

Impact of Neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab on Breast Tumor Downsizing for Patients with HER2+ Breast Cancer: Single-Arm Prospective Clinical Trial.

BACKGROUND: The impact of abbreviated neoadjuvant regimens for HER2+ breast cancer on rates of breast conservation therapy (BCT) is unclear. We aimed to determine BCT rates in a single-arm prospective trial of neoadjuvant paclitaxel/trastuzumab/pertuzumab (THP) in patients with stage II or III HER2+ breast cancer. STUDY DESIGN: BCT eligibility was prospectively recorded before and after THP. Pre- and posttreatment mammogram and breast ultrasound were required; breast MRI was encouraged. Patients with a large tumor to breast size ratio were eligible for downsizing. Multifocal/multicentric tumors, extensive calcifications, and contraindications to radiation were considered BCT contraindications. RESULTS: Overall, 92 patients who received neoadjuvant THP on trial were included. At presentation, 39 (42.4%) were considered eligible for BCT and 53 (57.6%) were not. BCT-eligible patients were older (median 54 vs 47 years, respectively; p = 0.006) and had smaller tumors by palpation (median 2.5 vs 3 cm, respectively; p = 0.004). Of 53 BCT-ineligible patients, 28 were candidates for tumor downsizing, whereas 25 had contraindications to BCT. Overall, 51 (55.4%) patients underwent BCT. Of the 28 patients who were candidates for downsizing, 22 (78.6%) became BCT-eligible after THP and 18 of 22 (81.8%) underwent BCT. In total, 44 of 92 (47.8%) patients experienced breast pathologic complete response (ypT0), including 11 of 25 (44.0%) patients with BCT contraindications at presentation. CONCLUSIONS: De-escalated neoadjuvant systemic therapy led to high BCT rates in this cohort. The impact of de-escalated systemic therapy on local therapy and outcomes in early stage HER2+ breast cancer warrants further investigation.

Assessment of the HER2DX Assay in Patients With ERBB2-Positive Breast Cancer Treated With Neoadjuvant Paclitaxel, Trastuzumab, and Pertuzumab.

Importance: Patients with early-stage ERBB2 (formerly HER2)-positive breast cancer (ERBB2+ BC) who experience a pathologic complete response (pCR) after receiving neoadjuvant therapy have favorable survival outcomes. Predicting the likelihood of pCR may help optimize neoadjuvant therapy. Objective: To test the ability of the HER2DX assay to predict the likelihood of pCR in patients with early-stage ERBB2+ BC who are receiving deescalated neoadjuvant therapy. Design, Setting, and Participants: In this diagnostic/prognostic study, the HER2DX assay was administered on pretreatment tumor biopsy samples from patients enrolled in the single-arm, multicenter, prospective phase 2 DAPHNe clinical trial who had newly diagnosed stage II to III ERBB2+ BC that was treated with neoadjuvant paclitaxel weekly for 12 weeks plus trastuzumab and pertuzumab every 3 weeks for 4 cycles. Interventions and Exposures: The HER2DX assay is a classifier derived from gene expression and limited clinical features that provides 2 independent scores to predict prognosis and likelihood of pCR in patients with early-stage ERBB2+ BC. The assay was administered on baseline tumor samples from 80 of 97 patients (82.5%) in the DAPHNe trial. Main Outcomes and Measures: The primary aim was to test the ability of the HER2DX pCR likelihood score (as a continuous variable from 0-100) to predict pCR (ypT0/isN0). Results: Of 80 participants, 79 (98.8%) were women and there were 4 African American (5.0%), 6 Asian (7.5%), 4 Hispanic (5.0%), and 66 White individuals (82.5%); the mean (range) age was 50.3 (26.0-78.0) years. The HER2DX pCR score was significantly associated with pCR (odds ratio, 1.05; 95% CI, 1.03-1.08; P < .001). The pCR rates in the HER2DX high, medium, and low pCR score groups were 92.6%, 63.6%, and 29.0%, respectively (high vs low odds ratio, 30.6; P < .001). The HER2DX pCR score was significantly associated with pCR independently of hormone receptor status, ERBB2 immunohistochemistry score, HER2DX ERBB2 expression score, and prediction analysis of microarray 50 ERBB2-enriched subtype. The correlation between the HER2DX pCR score and prognostic risk score was weak (Pearson coefficient, -0.12). Performance of the risk score could not be assessed due to lack of recurrence events. Conclusions and Relevance: The results of this diagnostic/prognostic study suggest that the HER2DX pCR score assay could predict pCR following treatment with deescalated neoadjuvant paclitaxel with trastuzumab and pertuzumab in patients with early-stage ERBB2+ BC. The HER2DX pCR score might guide therapeutic decisions by identifying patients who are candidates for deescalated or escalated approaches.

Surgical management of supravalvar aortic stenosis with coronary artery involvement.

Supravalvar aortic stenosis is characterized by an obstruction of the left ventricular outflow tract distal to the aortic valve. Its association with left main coronary artery stenosis is well known but right coronary artery involvement has not been reported. We describe two cases of supravalvar aortic stenosis with coronary artery stenosis and its surgical management.

Inflammatory pseudotumor arising from the right ventricular outflow tract causing pulmonary stenosis.

Inflammatory pseudotumor (also known as inflammatory myofibroblastic tumor) is an uncommon spindle cell lesion that was initially recognized in the lung and is now known to occur in virtually every major organ of the body. We report a case of a seven-year-old male who had an inflammatory pseudotumor of the right ventricular outflow tract involving the pulmonary valve causing pulmonary stenosis.