Prostate-Specific Membrane Antigen-Avid Neurofibroma Mimicking Cutaneous Metastasis in Metastatic Castration-Resistant Prostate Cancer on 18 F-PSMA-1007 PET/CT.

ABSTRACT: The occurrence of cutaneous metastases in prostate cancer is exceedingly rare. Many benign lesions and nonprostatic cancers can express the prostate-specific membrane antigen (PSMA). They can potentially mimic metastasis of prostate cancer and lead to misinterpretation of PSMA PET/CT findings. Additionally, it has significant management and prognostic implications. We present a rare case of an 88-year-old man with metastatic castration-resistant prostate cancer who showed a PSMA-expressing subcutaneous nodule in the scalp on 18 F-PSMA-1007 PET/CT, raising the suspicion of cutaneous metastasis. However, its biopsy revealed a neurofibroma, altering the disease prognosis and management.

Topical antibiotics in the prevention of port-site infection after elective day care laparoscopic cholecystectomy.

BACKGROUND: Wound-related infections and complications are rare after day care laparoscopic cholecystectomy (LC). They can have a significant adverse impact on the postoperative course after an uneventful elective LC. The use of topical antibiotics over the port site may prevent such complications. MATERIALS AND METHODS: This trial was conducted from January 2018 to June 2019. Two hundred and fifty patients who met the inclusion and exclusion criteria were included in the study. They were randomized into the topical antibiotic group (Group A, n = 125) and control group (Group B, n = 125). All patients underwent four-port LC. Mupirocin 2% topical antibiotic ointment was applied to all four-port sites in Group A, whereas no topical antibiotic was used in Group B. One dose of prophylactic systemic antibiotics was given to all patients in both groups. RESULTS: The mean age was 43.22 ± 12.7 years in Group A and 43.44 ± 12.5 years in Group B. The comorbidities and the other variables were comparable between the two groups. The port-site infection (PSI) was observed in one patient in Group A and three patients in Group B, which was statistically nonsignificant (P = 0.622). The mean time of detection of infection was 4.75 ± 1.7 days. All the infections were superficial surgical site infections. Microbiological swabs culture of the infected wounds yielded no growth of bacteria. CONCLUSION: The PSI after LC is very less. The use of topical antibiotics to prevent PSIs after LC could not be established.

Preliminary results of hypofractionated radiotherapy in breast cancer in Chandigarh, India: single-centre, non-inferiority, open-label, randomised, phase 3 trial.

Background: Globally, most of the randomised trials with hypofractionation in patients with breast cancer have used 3-dimensional conformal radiotherapy technique (3D-CRT). As facilities for 3D-CRT technique may not be available in low-resource settings, there is a need to see if hypofractionation is feasible and safe with 2-dimensional (2-D) technique. In this study, we compared a 3-week radiation schedule with a 2-week schedule of hypofractionated radiotherapy in patients with breast cancer with 2-D technique. Methods: The current study was an open-label, randomised, phase 3 trial. Patients with breast cancer, stage I-III, post mastectomy or after breast conservative surgery who needed adjuvant locoregional radiotherapy were randomised in the Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India; to 34Gy in 10 fractions over 2 weeks (2-week arm) or 35Gy in 15 fractions over 3 weeks to the chest wall and 40Gy/15#/3wks to breast and supraclavicular fossa (3-week arm). Boost dose when indicated was 8-10Gy/2-4#/2-4 days in both the arms. Patients were planned on a 2-dimensional (2D) simulator with 2 tangential fields to breast/chest wall and incident supraclavicular fossa field. Acute toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) grading scale. Assessments were carried out weekly during radiotherapy and at 4 weeks after treatment by the physician. Cosmetic outcome was assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG scale. The toxicity rates between the two arms were compared using Fisher's exact tests. The trial was approved by institutional ethics committee and registered with ClinicalTrials.gov, number NCT04075058. Findings: This study included 1121 eligible patients from June 2015 to December 2020. Median follow-up was 35 months (6-84 months). Mean age was 48 years (24-75 years). The patient characteristics were comparable between the two arms except for more mastectomies in the 3-week arm and more node-positive patients in the 2-week arm. There were more oestrogen receptor-positive tumors in the 3-week arm. Acute skin toxicities were comparable between the two arms. Grade 2 and 3 skin toxicity was 100 (18%) and 82 (15%); and 16 (3%) and 12 (2%) in the 3-week and 2-week arm (p = 0.21), respectively. Cosmetic outcome was assessed as Excellent or Good for 89% of patients in the 3-week arm as compared to 94% in the 2-week arm (p = 0.004). Interpretation: The two radiation schedules were comparable in terms of acute skin toxicity. The cosmetic outcome was better with the 2-week schedule. The preliminary findings indicate 2-week radiotherapy schedule with 2-D technique was better than the 3-week schedule in patients with breast cancer. However, disease outcomes and late-term toxicities need to be further checked. Funding: This study was funded by Science and Engineering Research Board (SERB), India.

Assessment of left ventricular dysfunction by strain echo in primary hyperparathyroidism and its reversal after parathyroidectomy.

BACKGROUND: Strain echocardiography is a highly sensitive modality for detecting myocardial disease at an early stage. Therefore, we aim to evaluate subclinical left ventricular dysfunction in primary hyperparathyroidism (PHPT) patients with myocardial strain imaging in addition to conventional echocardiography and to look for its reversal after parathyroidectomy (PTx). METHODS: Thirty patients who underwent curative parathyroidectomy for PHPT were included. All patients were evaluated with M mode echo, 2D echo and strain imaging before and 6 months after PTx. Left ventricular ejection fraction, left ventricular diastolic dysfunction, left ventricular hypertrophy (LVH), Global Longitudinal Strain (GLS) and global circumferential strain (GCS) were recorded. RESULTS: On M mode echo, LVH was present in 15 patients and 8 of them improved completely after PTx (p < 0.038). Incidence of systolic and diastolic dysfunction on 2D echo was 10% and 13.3% respectively; while myocardial strain imaging showed impaired systolic function in 46.7% patients. Hence, compared to conventional 2D echo, strain imaging showed 36.7% high detection rate of subnormal cardiac function. There was improvement in left ventricle dysfunction (p = 0.083), GLS and GCS (p = 0.034) after PTx. Serum parathormone demonstrated a strong positive correlation with change in GLS and GCS (p = 0.013, p = 0.126) while serum calcium showed a weak correlation with change in GLS and GCS following surgery. CONCLUSION: Myocardial strain imaging should be considered for all PHPT patients as early identification of subclinical ventricle dysfunction provides an opportunity for an early intervention and thereby preventing development of irreversible LV dysfunction.

Mandibular guiding flange prosthesis to guide mandibular deviation following partial mandibulectomy and partial maxillectomy for squamous cell carcinoma: A case report.

ABSTRACT: Squamous cell carcinoma is one of the most prevalent cancers affecting the oral cavity. Rehabilitation following surgical treatment requires a multidisciplinary approach and care. Multiple disabilities such as dysarthria, dysphagia, unesthetic appearance, and psychosocial disorders following the surgery for carcinoma can greatly impact the quality of life of such patients, thereby necessitating multidisciplinary intervention. The clinician has to wait for the healing of the lesion and the effects of radiotherapy to be dwindled in case a secondary osseous grafting is planned. During this time lag until a more definitive prosthesis is planned, an interim prosthesis is must to correct the mandibular deviation due to the unilateral muscular pull. This case presentation describes the utilization of guiding flange prosthesis (GFP) as an interim modality for the establishment of a stable and functional maxillomandibular relationship following combined ipsilateral partial mandibulectomy and maxillectomy.

HYPofractionated Adjuvant RadioTherapy in 1 versus 2 weeks in high-risk patients with breast cancer (HYPART): a non-inferiority, open-label, phase III randomised trial.

BACKGROUND: Breast cancer is the most common cancer in women. Radiotherapy is an important part of breast cancer treatment after surgery. Breast cancer radiotherapy is usually delivered in 3-5 weeks. This is a long duration for women with breast cancer to stay away from the family and work. We wanted to reduce this duration so that the wages loss and the logistics can be minimised for these patients. Hypofractionation, i.e. high dose per fraction, is delivered in a smaller number of days. In this study, we will compare a 1-week schedule of hypofractionated adjuvant whole breast/chest wall and/or regional nodal radiotherapy against 2 weeks for locoregional disease control, toxicities, quality of life (QoL), survival and second cancers after primary surgery in patients with breast cancer. METHODS: Eligible patients with breast cancer after mastectomy or breast conserving surgery (BCS) will be treated with a radiotherapy dose of 26 Gy in 5 fractions over 1 week in the study arm and 34 Gy in 10 fractions over 2 weeks in the control arm. The primary endpoint of this noninferiority study will be locoregional tumour control. Secondary endpoints will be early and late radiation toxicities, quality of life, contralateral primary tumours, regional and distant metastases, survival and second cancers. A total of 1018 patients will be randomised (1:1) to receive 1 week or 2 weeks of radiotherapy. An event-driven analysis will be performed after at least 94 patients have documented locoregional recurrences. Acute radiation toxicity will be assessed and scaled according to the RTOG grading system. Late radiation toxicity will be assessed with the Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer late radiation morbidity scale. Cosmetic assessment will be done using Harvard/NSABP/RTOG breast cosmesis grading scale at baseline and 3 and 5 years. QoL will be assessed with EORTC QLQ-30 and EORTC QLQ-BR 23 at baseline and 3 and 5 years. DISCUSSION: Hypofractionation reduces treatment time to half while maintaining breast cosmesis and gives control rates equal to conventional fractionation. This is possible because breast tissue can tolerate high dose per fraction. In this study, we presume that 1-week radiotherapy will be non-inferior to 2 week radiotherapy, i.e. disease control will be similar with both the schedules without additional side effects, and QoL of these patients will be maintained. If we are able to achieve these outcomes, then patients will be able to complete their radiotherapy in less duration. There is not much data on regional nodal irradiation with hypofraction in breast cancer. We have used hypofraction for regional nodal irradiation in the past and not encountered any safety issue. If we are able to prove that late-term effects are comparable in the two schedules, it will make the radiation oncologist confident about hypofractionation in breast cancer. As breast cancer is a leading cancer in females and radiation therapy is an integral part of its local management, hypofractionation will help radiation centres worldwide to meet the growing need for radiation treatment in breast cancer, particularly in developing countries where resources are limited. It will also reduce the financial burden on the patient and family. Since we will treat these patients with both simple and complex radiotherapy techniques, it will also be possible for the low-income countries to follow this trial without needing a high-end or expensive radiotherapy equipment as the planning and treatment process will be very simple. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov ID NCT04472845 and CTRI with REF/2020/09/037050.

68 Ga-PSMA-11 Uptake in a Large Fibroadenoma in a Male Axillary Accessory Breast.

ABSTRACT: Prostate-specific membrane antigen PET imaging has revolutionized the role of prostate cancer diagnosis and management, with very high sensitivity and specificity. To prevent misdiagnosis and for accurate therapy planning, prostate-specific membrane antigen (PSMA) uptake in nonprostatic diseases needs to be recognized correctly. Besides the physiological PSMA expression, 68 Ga-PSMA-11 uptake has been mentioned in multiple oncological and nononcological lesions. The present case report exhibits 68 Ga-PSMA-11 uptake in fibroadenoma in a male accessory breast in the right axillary region.

Bugs' eyes and black monsters: Ascitic fluid cytology in an elderly male with hematochezia.

Anorectal malignant melanomas are rare, accounting for less than 2% of all melanomas. Malignant effusions developing secondary to malignant melanoma are highly uncommon. Herein, we present the cytomorphological features of a metastatic anorectal malignant melanoma presenting with ascites at the initial clinical presentation.

Dual functionality of pyrimidine and flavone in targeting genomic variants of EGFR and ER receptors to influence the differential survival rates in breast cancer patients.

Breast cancer ranks as one of the most prevalent forms of cancer and stands as the primary global cause of mortality among women. Overexpression of EGFR and ER receptors or their genomic alterations leads to malignant transformation, disease aggression and is linked to poor patient survival outcomes. The clinical breast cancer patient's genomic expression, survival analysis, and computational drug-targeting approaches were used to identify best-hit phytochemicals for therapeutic purposes. Breast cancer patients have genomic alterations in EGFR (4%, n = 5699) and ER (9%, n = 8461), with the highest proportion being missense mutations. No statistically significant difference was observed in the patient survival rates between the altered and unaltered ER groups, unlike EGFR, with the lowest survival rates in the altered group. Computational screening of natural compound libraries (7711) against each EGFR (3POZ) and ER (3ERT) receptor shortlists the best-hit 3 compounds with minimum docking score (ΔG = -7.9 to -10.8), MMGBSA (-40.16 to -51.91 kcal/mol), strong intermolecular H-bonding, drug-like properties with least kd, and ki. MD simulation studies display stable RMSD, RMSF, and good residual correlation of best-hit common compounds (PubChem ID: 5281672 and 5280863) targeting both EGFR and ER receptors. In vitro, studies revealed that these common drugs exhibited a high anti-proliferative effect on MCF-7 and MDA-MB-231 breast cancer cells, with effective IC50 values (15-40 µM) and lower free energy, kd, and ki (5281672 > 5280863 > 5330286) much affecting HEK-293 non-cancerous cells, indicating the safety profile. The experimental and computational correlation studies suggest that the highly expressed EGFR and ER receptors in breast cancer patients having poor survival rates can be effectively targeted with best-hit common potent drugs with a multi-target therapeutic approach. Insight Box: The findings of this study provide valuable insights into the genomic/proteomic data, breast cancer patient's survival analysis, and EGFR and ER receptor variants structural analysis. The genetic alterations analysis of EGFR and ER/ESR1 in breast cancer patients reveals the high frequency of mutation types, which affect patient's survival rate and targeted therapies. The common best-hit compounds affect the cell survival patterns with effective IC50, drug-like properties having lower equilibrium and dissociation constants demonstrating the anti-proliferative effects. This work integrates altered receptor structural analysis, molecular interaction-based simulations, and ADMET properties to illuminate the identified best hits phytochemicals potential efficacy targeting both EGFR and ER receptors, demonstrating a multi-target therapeutic approach.

A fatal case of Aeromonas jandaei necrotizing fasciitis.

Introduction: Necrotizing soft tissue infections (NSTIs) are associated with a fulminating course because of their rapid destruction of tissue planes underlying the skin. Aeromonas -associated monomicrobial NSTIs are usually associated with exposure to fresh water, particularly among agricultural workers and fish handlers. Albeit uncommon in incidence, urgent medical and surgical intervention are required once a diagnosis has been made. Case report: A 40-year-old male patient, a known case of alcoholic liver disease, presented to the emergency department with pain and diffuse swelling of bilateral lower limbs, which quickly progressed to form blackish discolouration and blebs. Blood for preliminary haematological and biochemical investigations, as well as fluid draining from blebs, were sent for microbiological investigation. The Gram stain revealed occasional neutrophils and Gram-negative bacilli, and pure growth in aerobic culture was identified as Aeromonas jandaei by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The patient was started on empirical antimicrobials, although lesions continued to progress and he ultimately succumbed within 12 h of hospital admission. Conclusion: As appropriate antimicrobial therapy and early surgical intervention are required for management of the same, occupational exposure and the fulminant course should raise suspicion of Aeromonas -associated infections.

Modified Enhanced Recovery After Surgery (ERAS) Protocol Versus Non-ERAS Protocol in Patients Undergoing Emergency Laparotomy for Acute Intestinal Obstruction: A Randomized Controlled Trial.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a multimodal approach with promising results in improving patient outcome. Only recently, is evidence emerging highlighting how similar principles of care can be applied to patients undergoing emergency abdominal surgery. METHODS: A randomized controlled trial was conducted from November 2021 to April 2022 at PGIMER Chandigarh, which is a leading tertiary care hospital in northern India. 60 patients with acute intestinal obstruction requiring emergency laparotomy were randomized and assigned to ERAS or Non-ERAS group. ERAS protocol with some modifications was applied. Primary endpoints were post-operative hospital stay. Secondary end points were morbidity, 30-day readmission and mortality rate. Data analysis was done using SPSS 22.0. Independent t test or Mann-Whitney test and Chi-square or Fisher-exact test were used for analysis. RESULTS: A significant 3-day reduction in hospital stay was observed in ERAS compared to non-ERAS group (median (interquartile range) 5.50 (4.75-8.25) vs 8.0 (6.0-11.0) p = 0.003) with no difference in 30-day readmission rate, mortality rate and complication rate (according to Clavien-Dindo classification). ERAS group was associated with early recovery of gastrointestinal functions including time to first passage of flatus (p < 0.001), stools (p = 0.014), early ambulation (p < 0.001), time to first fluid diet (p < 0.001), solid diet (p = 0.001) and reduced nasogastric tube reinsertion rates (p = 0.01) despite its early removal. CONCLUSION: ERAS with some modifications can be applied in patients with intestinal obstruction. Thus, we can expedite post-operative recovery and early regain of gastrointestinal function with decreased hospital stay, comparable morbidity and mortality. Further studies are needed to assess ERAS role in emergency gastrointestinal surgeries. Trial registration Ctri.gov Identifier: CTRI/2022/04/042156.

Effect of Preoperative Carbohydrate Drink and Postoperative Chewing Gum on Postoperative Nausea and Vomiting in Patients Undergoing Day Care Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) causes an unexpected prolonged hospital stay after ambulatory surgery. Novel measures such as preoperative loading of oral carbohydrates and postoperative chewing gum have recently gained momentum for postoperative recovery. This study evaluated the effects of preoperative carbohydrate loading and postoperative chewing gum (CG) on PONV after daycare laparoscopic cholecystectomy (LC). METHODS: A total of 100 patients were randomized to group A (preoperative carbohydrate loading with 200 ml of water with 25 g of carbohydrate and postoperative chewing gum (CG) when the patient responded to his/her name) and group B (standard care). The incidence of PONV and pain was assessed by using visual analogue scale. Quality of recovery (QoR-15) was assessed by using QoR15 questionnaire at 6 h, 24 h and 48 h after surgery. RESULTS: The incidence of PONV and pain was lower in group A; however, it was not significant (p > 0.05). The severity of PONV, pain and the need for rescue antiemetic was significantly lower in group A (p < 0.05). The episodes of PONV and required dose of antiemetic were less in group A. Group A also had a significantly higher QoR-15 score at all time points (p < 0.001). Preoperative dyspepsia was also noticed as a significant confounding predictor for postoperative vomiting. CONCLUSION: Preoperative carbohydrate drinks and early postoperative CG reduces the severity of PONV and requirement of antiemetics in patients undergoing LC. Hence, these simple measures can be used as a standard of care to optimize perioperative care in patients undergoing daycare surgery.

IL-17 A correlates with disease progression in papillary thyroid carcinoma.

BACKGROUND: Cancer progression can be promoted by chronic inflammation. Local immune response may be associated with favourable or unfavourable prognosis of Papillary Thyroid Carcinoma (PTC). Regulatory T (Treg) cells and T helper 17 (Th17) cells exert opposing function and their balance may have a vital role in promotion of tumor growth. Treg cells in tumor microenvironment (TME) may promote tumor progression and reduced survival of patients. Whereas, Th17 cells can promote or inhibit tumor progression depending on phenotypic characteristics of tumor. In this study, we aimed to analyse the kind of immune response developed and its prognostic impact in future therapeutics. METHODS: Cytometric Bead Array (CBA) analysis of pro and anti-inflammatory cytokines (IFN-gamma, IL-2, IL-6, IL-17 A, TNF-alpha and IL-4, IL-10) was done in 15 PTC irrespective of Lymphocytic Thyroiditis (LT) and 16 Hashimoto's Thyroiditis (HT) cases. Immunohistochemical expression of FoxP3 and IL-17 A was studied in 27 cases of PTC with LT. Whereas, quantitative gene expression of both was analysed in 10 cases. RESULTS: All the pro-inflammatory cytokines showed mild elevation in PTC with LT. On IHC, IL-17 A expression was observed in 74% PTC with LT. Whereas, FoxP3 was present in only 40% cases. Also, IL-17 A expression was significantly associated with age group (> 45 years), tumor size ≤ 1 cm and disease progression. CONCLUSIONS: Increased expression of cytokines suggested correlation between inflammatory factors and progression of thyroid tumors. Along with this, the balance between IL-17 A and FoxP3 may play an important role in PTC development, prognosis and future management.

Effect of intraperitoneal magnesium sulfate in the prevention of postoperative pain in daycare laparoscopic cholecystectomy - A prospective randomized controlled trial.

This study evaluated the efficacy of intraperitoneal magnesium sulfate (MgSO4) in preventing postoperative pain after elective laparoscopic cholecystectomy (LC). It is a prospective, double-blinded, placebo-controlled, randomized trial which included 64 patients who underwent LC. Patients were equally randomized into Groups A and B. MgSO4 and normal saline were instilled in subdiaphragmatic space in Groups A and B, respectively, after creating pneumoperitoneum and before starting dissection. The Visual analogue Scale (VAS) was used to determine postoperative pain. Patients who received intraperitoneal MgSO4 had lower average VAS scores for the first 6 h postoperatively, and also, the time for the requirement of first analgesic was longer (3.6 ± 0.4 vs. 2.3 ± 1.0 h). The incidence of vomiting and the requirement for rescue antiemetic was also lower in Group A. Intraperitoneal instillation of MgSO4 reduces postoperative pain and vomiting following elective LC without incurring additional side effects.

Touch imprint smear: A prerequisite to obtain better quality and "true" tumor RNA in breast tissues.

BACKGROUND: RNA is the primary genetic material required for various molecular studies. RNA derived from breast tissue has low quality and quantity compared to that extracted from other tissues. Therefore, optimization of techniques for breast tissue RNA extraction is a challenging but essential requirement. METHODS: RNA was extracted from 60 samples of breast cancer after dividing them into 2 groups. Each tissue was divided into 2 halves for RNA extraction and histopathology respectively. In group 2 RNA was extracted after taking touch imprints whereas group1 was not subjected to any such procedure. Concentration and purity of RNA was assessed by using spectrophotometer and 1% agarose gel followed by RT-PCR for 18 S rRNA and CCND1 gene. RESULTS: Based on microscopic observations of imprints, group 2 samples were further subdivided into 2 subgroups. Group 2 A (n = 30) showing tumor in imprint smears were found to yield best concentration of pure RNA (1846.50 ng/µl and 1.92) as compared to group 2B (n = 15) with no malignancy in imprints (102.61 ng/µl and 1.53). The correlation of imprint smears with their corresponding H&E-stained slides further leads to grouping of each group in 2 groups. RT-PCR analyses showed better melting peaks and high relative expression of CCND1 in group 2 A. CONCLUSION: Touch imprints may provide valuable information regarding presence or absence of tumor in tissue samples being used for extraction of genetic material. This approach can be used as easy, cheap and fast strategy to resolve the doubts associated with RNA being truly representative of the tumor.

Establishment and characterization of long-term human primary parathyroid tumor subclones derived from Indian PHPT.

The continuous cell line of epithelial human parathyroid cells has been proven difficult. Previously, PTH-C1 cell line was only established rat parathyroid tissue cell line known to express the parathyroid hormone-related peptide (Pthrp) gene. The paucity of continuous cell line of human parathyroid cells secreting parathyroid hormone (PTH) has imposed hurdle in in vitro assessment of the mechanisms involved in the control of parathyroid cell function and proliferation. The primary cell cultures of human parathyroid cells were derived from parathyroid adenoma tissue biopsy (n = 5). The cells were subsequently subcultured to maintained primary subclones. Karyotyping analysis was performed to analyze the genotypic identity of derived subclones. The expression of calcium-sensing receptor (CaSR) and intact parathyroid hormone (iPTH) were analyzed using immunocytochemistry and immunofluorescence. In the present study, we have used a defined condition medium to generate the continuous culture of human parathyroid cells derived from patients with parathyroid adenoma due to primary hyperparathyroidism. The subcultured primary subclones were maintained epithelial and polygonal morphology, doubling time of approximately 25 h, displaying a diploid chromosome number, and secretion of PTH. This cell line produces PTH and expresses the calcium-sensing receptor (CaSR) known to be involved in parathyroid function. Altogether these findings indicate the uniqueness of the human parathyroid cell line as an in vitro model for cellular and molecular studies on parathyroid physiopathology.

Visceral Obesity as a Predictor of Postoperative Complications After Pancreaticoduodenectomy.

INTRODUCTION: Obesity is associated with increased morbidity and mortality post surgery. The measurement of visceral obesity can predict postoperative outcomes after pancreaticoduodenectomy. METHODS: This is a prospective observational study. Visceral obesity was calculated by measuring the fat thickness in the retro-renal area by using a computed tomography scan. Visceral obesity was defined as retro-renal fat thickness (RRFT) of ≥ 2 cm. Patients were divided into two groups: Group-A (RRFT < 2 cm, non-obese) and Group-B (RRFT > 2 cm, obese). Demographic, clinical, and intraoperative variables were correlated with postoperative outcomes. RESULTS: Fifty-six patients were included in the study. Thirty-two patients were included in Group-A, and 24 patients were included in Group-B. The two groups had comparable outcomes. A total of 21 patients in Group-A (65.62%) and 17 patients in Group-B (70.83%) had comorbidities, including diabetes mellitus, hypertension, and coronary disease (p=0.680). American Society of Anesthesiologists (ASA) grading was comparable (p=0.927). BMI was also comparable (p=0.354). Type of pancreaticoduodenectomy, pancreatic texture, pancreatic duct diameter, and technique of pancreaticojejunostomy anastomosis were comparable. The mean operative time was longer in Group-B (362 ± 36.2 min vs. 298 ± 45.2 min) (p=0.001). Intraoperative blood loss was more in Group-B (312 ± 36.8 ml vs. 267 ± 23.7 ml) (p=0.001). The rates of postoperative pancreatic fistula and delayed gastric emptying were comparable (p=0.402 and p=0.134, respectively). The length of hospital stay was longer in patients in Group-B (p=0.004). There was one death in Group-B (obese group). CONCLUSION: Visceral obesity is a risk factor for postoperative complications after a pancreaticoduodenectomy.

Impact of age on outcomes in young women with breast cancer.

BACKGROUND: In this study, we compared outcomes in young and very young patients with breast cancer (BC). MATERIALS AND METHODS: Between January 1990 to December 2010, 414 young women (age ≤35 years) with BC were registered in the radiotherapy (RT) outpatient department. Patients were divided into young (31-35 years) and very young (18-30 years). They were compared for clinical, pathological characteristics, and treatment-related factors such as RT and systemic therapy. Outcomes compared between the two groups were locoregional recurrence rate (LRR), local recurrence-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and toxicities. LRFS, DFS, and OS were estimated using the Kaplan-Meier method. RESULTS: Out of 414 patients, 138 and 276 were very young and young, respectively. Clinical, pathological, and treatment characteristics were balanced between the two groups except for more patients in the young group who had pN3 disease and received hormonal therapy; 41 (15%) versus seven (5%) and 171 (62%) versus 62 (45%) in the very young group, respectively. Median follow-up was 84 months (range 12-363 months). LR was seen in 16 (11.6%) and 25 (9%) patients in the very young and young groups, respectively (p = 0.28). The hazard ratios for LR, disease recurrence, and death in the very young group relative to the young group were 1.11 (p = 0.25), 1.0 (p = 1.0), and 1.05 (p = 0.79), respectively. Estimated 10-year LRFS, DFS and OS were 80% versus 86%, 63% versus 61%, and 66% versus 64% in the very young and young groups, respectively. Lymphedema, cardiac toxicity, and second malignancy developed in seven (5%) versus 23 (8%), one (1%) versus three (1%), and seven (5%) versus 18 (7%) patients in the very young and young groups, respectively. CONCLUSION: In very young and young patients with BC, there was no significant difference in LRR, LRFS, DFS, or OS. Toxicities were also comparable between the two groups.

Effect of aspirin on the TNF-α-mediated cell survival and death pathways in breast cancer.

OBJECTIVES: Aspirin is an anti-inflammatory drug commonly used as an analgesic and in cardiovascular disorders. However, many studies have highlighted its anti-cancer properties, especially in colorectal, lung, head and neck, and breast cancers. In this work, we tried to study the effect of aspirin on the TNF-α-mediated cell survival and death pathways in two cell lines representing two different subtypes of breast cancer. TNF-α-mediated stimulation of a cell can result in its proliferation via the NF-κB pathway or its death via either apoptosis or a programmed form of necrosis called necroptosis. The latter is believed to come into the picture only when apoptosis is inhibited. METHODS: In this work, we studied the effect of aspirin on the TNF-α-mediated cell survival pathway and observed a decrease in expression of the NF-κB pathway regulators, its nuclear translocation, and phosphorylation in a dose-dependent manner. The effect of aspirin on the TNF-α-mediated cell death showed significant cytotoxicity at the higher doses (5-20 mM) of aspirin in both the breast cancer cell lines. The effect of aspirin on necroptosis was investigated after stimulating the cells with TNF-α and inhibiting apoptosis using Z-VAD-FMK. RESULTS: Though no significant effect was noted in breast cancer cell lines, the above protocol successfully induced necroptosis in L929, i.e., a positive control cell line for necroptosis having an intact necroptosis machinery. Even when combined with the chemotherapeutic drugs, the above regime failed to induce any significant necroptosis in breast cancer cells but was found effective in L929. CONCLUSIONS: Overall, the findings show that while aspirin has the potential to inhibit the TNF-α-mediated cell survival pathway, it does not help sensitize breast cancer cells to necroptotic cell death induction.