Comparative analysis of mutational patterns in triple negative breast cancer before and after neoadjuvant chemotherapy in patients with residual disease.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor survival compared to other subtypes. Patients with residual disease after neoadjuvant chemotherapy (NAC) face an increased risk of relapse and death. We aimed to characterize the mutational landscape of this subset to offer insights into relapse pathogenesis and potential therapeutic targets. We retrospectively analyzed archived paired (pre- and post-NAC) tumor samples from 25 patients with TNBC with residual disease using a targeted 72-gene next-generation sequencing panel. Our findings revealed a stable mutational burden in both pre- and post-NAC samples, with a median count of 12 variants (IQR 7-17.25) per sample. TP53, PMS2, PTEN, ERBB2, and NOTCH1 variants were observed in pre-NAC samples predominantly. Notably, post-NAC samples exhibited a significant increase in AR gene mutations, suggesting potential prognostic and predictive implications. No difference in mutational burden was found between patients who did and did not receive platinum (p = 0.94), or between those with and without recurrence (p = 0.49). We employed K-means clustering to categorize the patients based on their variant profiles, aiding in the prediction of possible patterns associated with recurrence. Our study was limited by its small sample size and retrospective design, suggesting the need for further validation in larger prospective cohorts.

Dose-Dense Docetaxel-Cyclophosphamide and Epirubicin-Cisplatin(ddDCEP): Analysis of an Alternative Platinum-Containing Regimen in 116 Patients with Early Triple Negative Breast Cancer.

We assessed the efficacy, tolerability, and cost-effectiveness of a novel neoadjuvant regimen comprising docetaxel-cyclophosphamide alternating with epirubicin-cisplatin (ddDCEP) administered biweekly for 16 weeks in 116 patients with early triple-negative breast cancer. This regimen achieved a high pathological complete response (ypT0/TisN0) rate of 55.2% and favorable survival outcomes (30-month event-free survival, 91.2%; overall survival, 97%). Febrile neutropenia was observed in 4.3% of patients, and 98% completed at least six of eight cycles. ddDCEP was more cost-effective than contemporary carboplatin-based regimens. This novel approach offers an economically viable and effective alternative to current chemoimmunotherapy regimens, and merits further investigation.

Adrenocortical Carcinoma: a Therapeutic Challenge - 44 Cases from a Single Tertiary Care Center in India.

This study was conducted among patients with adrenocortical carcinoma (ACC) to analyze their clinico-pathological profile, management outcomes, and risk factors for local recurrence, systemic metastasis, and survival. The data of patients with ACC who were managed at a single institution between January 2004 and December 2016 was retrospectively collected and analyzed using STATA 13.1. Forty-four patients with a diagnosis of ACC were included in the study. The mean age at presentation was 38.5 ± 14.6 (9-74) with a male preponderance. Functioning tumors represented 59.1% (n = 26), cortisol being the most common hormone secreted. Forty patients (90.9%) underwent surgery, 14 (35%) of whom required an en bloc resection of adjacent organs. Fifteen (37.5%) received radiation (RT) to the postoperative bed while chemotherapy and mitotane were administered in 12 (27.3%) and 9 (20.5%) respectively. The mean follow-up was 34.3 ± 32.7 months. Twelve (30%) patients developed local recurrence, 21 (55.3%) had systemic metastasis, and 15 (34.1%) expired. The mean 1-year and 5-year overall survival rates were 77% and 65.7% respectively. On multivariate analysis, patients with ENSAT stage III/IV were significantly associated with local recurrence (p = 0.011) and metastasis (p = 0.037). Age > 50 (p = 0.003) and ENSAT III/IV (p = 0.017) were significantly associated with mortality on univariate analysis but not on multivariate analysis. In our study population, patients presented at a younger age with a male preponderance. Ninety percent underwent surgery, a subset (35%) requiring resection of adjacent organs to ensure R0 resection. Patients presenting at ENSAT stage I/II have better outcomes.

Clinical Profile and Mutations Associated with Multiple Endocrine Neoplasia-Type1 (MEN1) and Their First-Degree Relatives at Risk of Developing MEN1: A Prospective Study.

Multiple Endocrine Neoplasia type-1 (MEN1) is an autosomal dominant disorder with a combined occurrence of tumours of parathyroid glands, pancreatic islets, and anterior pituitary. About 90% of these patients carry mutations in the MEN1 gene, though the spectrum is not well defined in India. Forty clinically suspected cases of MEN1 were enrolled prospectively over six years; 32 patients (23 index-cases and nine affected relatives) with≥2 classical endocrine tumours of MEN1 were considered definite, and eight were categorised as 'MEN1-like'. Details of their clinical presentation, treatment and mutational analysis including MEN1 gene, 3' and 5' untranslated regions (UTR) of MEN1, CDKN1B, and CaSR genes were collated. Asymptomatic first-degree relatives were also screened. Among the 32 definite MEN1 patients, all had primary hyperparathyroidism, 22 (68.7%) had gastroentero-pancreatic neuroendocrine tumours, and 21 (66%) had pituitary adenoma. Of the 23 definite index-cases, 13 (56.5%) carried mutations in the MEN1 gene. Five of nine affected first-degree relatives (55.5%), and four of 10 asymptomatic relatives (40%) also had MEN1 mutations. Seven of 10 MEN1 mutation-negative definite index-cases harboured p.V109G polymorphism in the CDKN1B gene. All eight MEN1-like cases were negative for mutations and large deletions in MEN1, mutations in 3' and 5' UTR of MEN1, CaSR and CDKN1B genes. The study has helped to clearly document the pattern of mutations among Indian MEN1 patients. However, the absence of MEN1 mutation in ~44% of cases and the presence of p.V109G polymorphism in CDKN1B gene raise the question whether such polymorphisms could independently contribute to pathogenesis.

Does Baseline PTH Influence Recovery of Bone Mineral Density, Trabecular Bone Score and Bone Turnover Markers? A Prospective Study Following Curative PArathyroidectomy in Primary Hyperparathyroidism.

OBJECTIVE: This prospective study was carried out to assess trabecular bone score, bone mineral density (BMD), and bone biochemistry in Indian subjects with symptomatic primary hyperparathyroidism (PHPT), and to study the influence of baseline parathyroid hormone (PTH) on recovery of these parameters following curative surgery. METHODS: This was a 2-year prospective study conducted at a tertiary care centre in southern India. Baseline assessment included demographic details, mode of presentation, bone mineral biochemistry, BMD, trabecular bone score (TBS), and bone turnover markers (BTMs). These parameters were reassessed at the end of the first and second years following curative parathyroid surgery. RESULTS: Fifty-one subjects (32 men and 19 women) with PHPT who had undergone curative parathyroidectomy were included in this study. The mean (SD) age was 44.6 (13.7) years. The TBS, BTMs, and BMD at lumbar spine and forearm were significantly worse at baseline in subjects with higher baseline PTH (≥250 pg/mL) when compared to the group with lower baseline PTH (<250 pg/mL). At the end of 2 years, the difference between high versus low PTH groups (mean ± SD) persisted only for forearm BMD (0.638±0.093 versus 0.698±0.041 g/cm2; P =.01). However, on follow-up visits in the first and second year after curative parathyroidectomy, there was no significant difference in BTMs, BMD at the femoral neck, lumbar spine, and TBS between the 2 groups stratified by baseline PTH. CONCLUSION: The BMD at the forearm remained significantly worse in individuals with high baseline PTH even at 2 years after surgery, while other parameters including TBS improved significantly from baseline. ABBREVIATIONS: 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; BMI = body mass index; BTMs = Bone turnover markers; CTX = C-terminal telopeptide of type 1 collagen; DXA = dual energy X-ray absorptiometry; P1NP = N-terminal propeptide of type 1 procollagen; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TBS = trabecular bone score.

Seesawing end-tidal carbon dioxide: portent of critical carbon dioxide embolism in retroperitoneoscopy.

An abrupt increase in end-tidal CO2 (EtCO2; from 35 to 58 mm Hg) followed by a sudden fall (to 18 mm Hg) was noted during retroperitoneoscopic adrenalectomy under general anaesthesia in a 23-year-old patient with adrenal hyperplasia. This was accompanied by hypotension (systolic blood pressure of 60 mm Hg), desaturation (88% SpO2) and ST depression (3.5 mm). The patient was resuscitated with fluids and vasopressor drugs and about 4 mL of air was aspirated through the central venous catheter, confirming the diagnosis of an intraoperative gas embolism. Later, a rent in the adrenal vein extending into the inferior vena cava was discovered and sutured. The blood pressure, EtCO2, ST segment and pulse oximetry returned to normal after 15 min. This case demonstrates that gas embolism may transpire during retroperitoneoscopic adrenalectomy and an acute rise followed by a sharp fall in EtCO2 should alert the anaesthesiologist to this rare but potentially fatal complication.

Video Assisted Thoracoscopic Surgery (VATS) for Excision of an Ectopic Anterior Mediastinal Intra-Thymic Parathyroid Adenoma.

Ectopic anterior mediastinal parathyroid adenoma is a rare cause of Primary Hyperparathyroidism (PHPT). Imaging studies such as Technetium-99m ((99m)Tc) sestamibi parathyroid scan along with a Single Photon Emission Computerized Tomogram (SPECT), and contrast enhanced Computerized Tomogram (CT) of the neck and thorax can precisely localize the ectopic mediastinal parathyroid adenoma. We report a 40-year-old gentleman who presented with persistent pain in the right shoulder following trivial trauma. His biochemical investigations showed an elevated serum calcium of 11.6mg% (Normal: 8.3-10.4 mg%) along with an elevated iPTH of 1443 pg/ml (normal: 8-70 pg/ml) which were suggestive of primary hyperparathyroidism. The localization studies revealed an ectopic cystic parathyroid adenoma in the anterior mediastinum that was not accessible from the neck. He underwent a Video Assisted Thoracoscopic (VAT) excision procedure with normalization of serum calcium and an uncomplicated recovery. The VAT approach is a successful minimally invasive technique for mediastinal parathyroidectomy.

Is TIRADS a practical and accurate system for use in daily clinical practice?

AIM: To assess the positive predictive value (PPV) and inter-observer agreement of Thyroid Imaging Reporting and Data System (TIRADS) as described by Kwak et al. MATERIALS AND METHODS: This was a prospective study wherein ultrasound was performed by two radiologists on patients with thyroid nodules >1 cm. The third radiologist interpreted archived images. Ultrasound features and TIRADS category were compared with cytology and surgical histopathology. PPV was calculated for all readers' combined assessment. Inter-observer agreement was calculated using linear weighted kappa. RESULTS: A total of 238 patients with 272 nodules of mean size 2.9 ± 1.7 cm were included. PPV for malignancy was 6.6%, 32%, 36%, 64%, 59%, and 91% for TIRADS 2, 3, 4a, 4b, 4c, and 5 categories, respectively. Inter-observer agreement was substantial [kappa (k) = 0.61-0.80] for assessment of nodule echogenicity, margins, calcification, and shape and good (k = 0.570, P < 0.001) for assessment of composition of the thyroid nodules. Overall agreement between observers was substantial for assigning TIRADS category [multi-rater weighted kappa coefficient (wt k) = 0.721, P < 0.001]. CONCLUSIONS: TIRADS is a simple and practical method of assessing thyroid nodules with high PPV and good inter-observer agreement.

Acute suppurative thyroiditis secondary to urinary tract infection by E. coli: a rare clinical scenario.

A 60-year-old woman with diabetes and symptomatic urinary tract infection presented to us with a painful neck swelling for 2 weeks. We discuss diagnostic and management issues in acute suppurative thyroiditis caused by Escherichia coli.

The Role of Magnesium in Post-thyroidectomy Hypocalcemia.

BACKGROUND: The purpose of this study was to determine the prevalence of hypomagnesemia in patients undergoing thyroidectomy and evaluate the relationship of hypomagnesemia with transient and severe hypocalcemia. MATERIALS AND METHODS: This was a prospective observational study of 50 patients undergoing thyroidectomy. Blood samples were collected pre- and postoperatively for calcium, albumin, magnesium, phosphorous and parathormone (PTH). Signs, symptoms of hypocalcemia and volume of intravenous fluids used perioperatively were documented. The statistical analysis was performed using STATA I/C 10.1. RESULTS: Preoperatively, twelve patients (24 %) had hypomagnesemia and one (2 %) hypocalcemia. On the first postoperative day, hypomagnesemia was seen in 70 % and hypocalcemia in 30 %. A similar trend was observed in the fall and rise of postoperative calcium and magnesium values (p = 0.41). Severe hypocalcemia was present in three patients (6 %). All three patients had a very low postoperative PTH (<2 pg/ml). Among them, two patients (66 %) had hypomagnesemia and their hypocalcemia responded to intravenous magnesium correction. Significant risk factors for postoperative hypocalcemia include a higher volume of fluid used perioperatively and low postoperative PTH (<8 pg/ml) (p = 0.01 and 0.03, respectively). CONCLUSION: Preoperative hypomagnesemia (24 %) was prevalent in this cohort of patients. Postoperative hypomagnesemia is a common event (70 %) following total thyroidectomy, and magnesium levels tend to mimic the calcium levels postoperatively. The cause of hypocalcemia post-thyroidectomy in this study is mainly a factor of parathyroid function and fluid status. Severe hypocalcemia is a rare event, and hypomagnesemia is associated in the majority of these patients. The role of magnesium correction to alleviate severe hypocalcemia needs to be further studied.

Adrenal incidentaloma caused by extramedullary haematopoiesis: conservative management is optimal.

We present a thalassaemic patient with extramedullary haematopoiesis in the adrenal gland, which is one of the rare sites of involvement. A 29-year-old man presented with a history of anaemia since childhood which required blood transfusion recently. On examination, he had pallor, icterus and splenomegaly with no other palpable abdominal mass. He was diagnosed to have ß-thalassaemia. Ultrasonography of the abdomen showed an incidental right adrenal mass with splenomegaly; CT revealed a large right adrenal mass with heterogeneous density. Adrenal adenoma, carcinoma and extramedullary haematopoiesis were considered in the differential diagnosis. After excluding a functioning tumour, the diagnosis was confirmed by ultrasound-guided biopsy. Since the patient was asymptomatic, the adrenal lesion was managed conservatively.

Paraneoplastic polyarthritis in association with metastatic neuroendocrince tumour of the adrenal gland.

Paraneoplastic polyarthritis is a rare manifestation described in association with various solid tumours. We describe the clinical presentation, diagnostic evaluation, differential diagnosis, and management of a 28-year-old woman who presented with fever, weight loss, and symmetrical polyarthritis, subsequently diagnosed to have a metastatic neuroendocrine tumour of the adrenal gland with paraneoplastic polyarthritis. Paraneoplastic polyarthritis must be considered in polyarthritis unexplained by common aetiologies. The unusual presentation of this case, alerts us about the atypical presentation of these tumours. To the best of our knowledge, this is the first case study of a neuroendocrine tumour presenting as paraneoplastic polyarthritis.

Metastatic parathyroid carcinoma treated with radiofrequency ablation: A novel therapeutic modality.

Parathyroid carcinoma (PCA), accounting for less than one per cent of all endocrine malignancies, is a rare cause of primary hyperparathyroidism. A diagnosis of parathyroid carcinoma may be challenging in the presence of localised disease and involves a histological diagnosis based on capsular, vascular, or perineural invasion or the presence of metastasis. Distant metastasis remains a rare presentation, with the lung being the most common site. Surgery remains the treatment of choice as radiotherapy and chemotherapy have proved to be of limited benefit in metastatic disease. This case reports suggests that radiofrequency ablation has the potential to be a novel and effective treatment option in these patients.