Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study.

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and 2 CCTA scans during the 2-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026 to 2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

Evaluating Patient Experience in a Multidisciplinary Breast Cancer Clinic: A Prospective Study.

Background: Multidisciplinary clinics (MDCs) are a care model in which patients see several physicians across specialties and/or other allied health professionals in a single appointment in a shared space. This study sought to better understand patients' experiences with breast cancer (BC) MDC. Methods: A total of 429 patients diagnosed with BC and seen in a MDC between November 2020 and November 2021 were invited to participate in a patient experience survey. Results: In total, 116 patient respondents (27%) with representative demographics described their experience. Most patients report feeling "somewhat prepared" for the BC MDC experience (67%, median = 3.7, interquartile range [IQR] = 1.9), but with variability. The major areas of positive feedback were that the MDC was convenient (89.3%), efficient use of time (65.2%), and a good way to get questions answered (65.2%). Major criticisms included that the MDC was overwhelming (16.1%) and/or too long (4.5%). When asked to rate the top three satisfaction areas of MDCs, patients chose seeing multiple providers during a single visit (80.4%), communication about the process before and throughout the MDC (48.2%), and inclusivity of their support system (38.4%). The highest rated dissatisfiers were the volume of information presented (42.9%) and patients' emotional comfort (anxiety/stress) during MDC appointment (30.2%). Overall, 83% of patients with BC rate the MDC experience as excellent (median = 4.8, IQR = 0.9) and would be "very likely" to recommend BC MDC (median = 4.8, IQR = 0.9). Conclusion: Patients value seeing multiple providers simultaneously in an environment inclusive of their support systems, which is described as convenient and efficient. Improving emotional distress is a key opportunity to improve patient experience.

Triple Negative Breast Cancer and Brain Metastases.

The treatment of metastatic breast cancer (MBC) has improved over the past decade, however prognosis continues to be mitigated by the fact that about 1 in 5 patients with MBC will develop brain metastases (BrM) during their metastatic disease course. 1 This number is even higher for patients with triple-negative breast cancer (TNBC), with studies showing as high as 40% of patients developing BrM. 2, 3 Studies have shown that TNBC portends a worse survival after a diagnosis of BrM compared with non-TNBC subtypes. 4 Given the unique location and biologic properties of BrM, treatment options have historically been limited. Challenges to the treatment of TNBC BrM include a lack of targeted therapies and difficulties in delivery of drug to the brain past the blood-brain barrier (BBB). Herein, we will review the advances in local and systemic therapies to most effectively treat patients with TNBC BrM, including therapies on the horizon currently in clinical trials.

A Rare Lesion at Rare Location: A Surgeon's Enigma.

Leiomyosarcoma of palate is a rare malignant spindle cell tumour in oral cavity. It is often misdiagnosed with other benign lesions like nodular fasciitis, clinical and histological similarity of rapid growth, rich cellularity, as the pathogenesis is unknown, which can make diagnosis and management challenging. The non-specific clinical, radiologic and pathological presentation of spindle cell tumours causes diagnostic difficulty due to similarities to granulation tissue, benign or malignant lesions in histologic and imaging features. Nevertheless, differentiation is important because the prognosis and treatment varies according to the type of tumor. NF is frequently evaluated by biopsy and also immunohistochemistry (IHC) which is very essential in cases of non-regressing lesions after biopsy. The present case report highlights the clinical and histopathologic challenges in a rare case of nodular fasciitis in the palate which initially diagnosed as granulation tissue and later confirmed as Grade l leiomyosarcoma on IHC.

Cryptococcosis presenting as anterior neck swelling in an immunocompetent man: a case report.

BACKGROUND: Cryptococcosis is caused by the encapsulated opportunistic yeast Cryptococcus neoformans. An immunocompromised host is more susceptible to the survival and dissemination of this yeast, which can occur to almost all organs of the body, especially the central nervous system, lungs, bone marrow, gastrointestinal tract, retina, and reticuloendothelial system. However, there are few reports of Cryptococcus causing infections ir immunocompetent hosts. CASE: A 70-year-old immunocompe tent man presented with swelling in the anterior neck region, which was diagnosed as cryptococcosis by fine needle aspiration cytology. CONCLUSION: Fine needle aspiration cytology plays a rapid, useful and important role in the diagnosis of cryptococcosis infection, especially in clinically unsuspected cases, and helps in timely therapeutic intervention.

Cytomorphological pattern analysis of tubercular lymphandenopathies.

BACKGROUND: The spectrum of morphological pattern in tubercular lymphandenopathies was observed to study the various cytomorphological patterns and their correlation with acid fast bacilli. METHODS: FNAC smears of 210 cases of granulomatous lymphadenitis stained with Giemsa, Pap and haematoxylin and eosin were used to analyze cytomorphological pattern and Zeihl Neelsen stained smears for acid fast bacilli (AFB) detection. RESULTS: 193 cases with necrotising granulomatous inflammation or positive acid fast bacilli were included. Age group 21-30 years was most common (38.3%) followed by age group 11-20 years (30.05%). Females constituted 66.3% of patients and 33.7% were male. Overall the most common pattern in present study was pattern A (Epitheloid granuloma with caseous necrosis 33.7% followed by pattern B (caseous necrosis with few scattered epitheloid histiocytes and lymphocytes) 31.1% and pattern C (caseous necrosis with suppurative inflammation) 30.6%, followed by pattern D (Caseous necrosis only) (3.6%) and pattern E (non necrotising epitheloid granuloma with positive acid fast bacilli) (1.03%). Acid fast bacilli were demonstrable in 175 cases (90.7%). Amongst the acid fast bacilli positive cases highest bacillary load 3+ grade was seen in pattern C in 6/59 (10.16%) cases. CONCLUSION: FNAC is a simple useful tool and should be attempted in all cases of lymphandenopathies. It helps in establishing a diagnosis of tubercular etiology based on its morphological patterns however demonstration of acid fast bacilli on aspirated material confirms the diagnosis.

Effects of Different Contraceptive Methods on Cervico-Vaginal Cytology.

INTRODUCTION: The vaginal flora of healthy adult women of reproductive age group constitutes predominantly Lactobacilli which inhibits the growth of other microorganisms (by maintaining acidic pH). The vaginal microflora is altered in favour of anaerobes in women using Intra Uterine Contraceptive Device (IUCD). Also, it can cause morphologic changes in both squamous and endocervical columnar cells. Similarly, the prevalence of vaginal lactobacilli is reduced among women using diaphragm-spermicide or spermicide alone. AIM: To study the effects of different contraceptive methods on cervical cytology and vaginal flora. MATERIALS AND METHODS: Two years prospective study included 120 women of reproductive age group using barrier, tubal ligation, IUCDs, Oral Contraceptive Pills (OCPs) and injectable methods of contraception and a control group including 60 women not using any contraceptive. Cervical and vaginal smears were obtained. Cervical smears were reported using the Bethesda system and Gram stained vaginal smears were scored using Nugent scoring. SPSS (Statistical Package for the Social Sciences) software for Windows Version 19.0 and test of significance applied was Chi-square test. RESULTS: The most common contraception used was barrier (68.3%) followed by tubal ligation (14.2%), IUCD (9.2%), OCPs (6.6%) and injectable (1.7%). The presenting complaints were pain lower abdomen (46.7%) followed by menstrual complaints (22.5%). Epithelium showed reactive changes (45%) followed by metaplasia (25%), koilocytotic change (5%), cytolytic effect (5%) and satellitosis (4.2%). Women showed normal flora in 51.7%, altered in 30% and bacterial vaginosis in 18.3%. CONCLUSION: Cervico-vaginal changes were more frequent in contraceptive users as compared to the control group.

Pattern of cancers amongst patients attending Himalayan Institute of Medical Sciences, Dehradun.

This hospital-based study seeks to find out the most common cancers amongst the patients attending Himalayan Institute of Medical Sciences (HIMS), Dehradun, situated in Uttaranchal, which has inadequate health care facilities and low socio-economical status. In our study, of the 20,247 cases reported in the pathology department from July 1996 to Dec. 2003, 18.57% cases were malignant. Male to female ratio was 1.7:1.Top five cancers in males were those of lung, larynx, non-Hodgkins lymphoma, oesophagus & stomach. Top five cancers in females were those of breast, cervix, gall bladder, ovary & oesophagus. Tobacco and alcohol related cancers predominated in males. Skin and soft tissue cancers and were also common amongst both genders. Patients mostly reported with cancers in advanced stages, which could be attributed to poor medical facilities and health awareness in this region.

Histopathological changes in gastric mucosa colonized by H. pylori.

Helicobacter pylori (H. pylori), infection has been linked to acute and chronic gastritis, non-ulcer-dyspepsia, peptic ulcer, gastric adenocarcinoma and gastric non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue (MALT). The epithelial changes in H. pylori colonized gastric mucosa are easy to recognize in routine Haematoxylin & Eosin stained sections and are so distinctive that they can serve as a helpful histological indicator for the presence of H. pylori in gastric biopsies. The histopathology of seventy-five gastric biopsies showing colonization by H. pylori was studied. Histologically, the H. pylori colonized gastric epithelium showed characteristic changes that were topographically related to the bacteria. These changes included irregular surface, epithelial pits, individual cell dropout and microerosion, which were specific for H. pylori colonization. These were absent in areas not colonized by H. pylori and in 20 consecutive H. pylori negative gastric biopsies seen during the same study period. As specific treatment for H. pylori infection is available, identification of H. pylori colonization in gastric biopsies should be attempted in all cases of gastritis, peptic ulcers and non-ulcer-dyspepsia.

Pharmacological benefits of selective modulation of cannabinoid receptor type 2 (CB2) in experimental Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that pervasively affects the population across the world. Currently, there is no effective treatment available for this and existing drugs merely slow the progression of cognitive function decline. Thus, massive effort is required to find an intended therapeutic target to overcome this condition. The present study has been framed to investigate the ameliorative role of selective modulator of cannabinoid receptor type 2 (CB2), 1-phenylisatin in experimental AD condition. We have induced experimental AD in mice by using two induction models viz., intracerebroventricular (i.c.v.) administration of streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose. Morris water maze (MWM) and attentional set shifting test (ASST) were used to assess learning and memory. Hematoxylin-eosin and Congo red staining were used to examine the structural variation in brain. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), nitric oxide levels (nitrites/nitrates), acetyl cholinesterase activity, myeloperoxidase and calcium levels were also estimated. i.c.v. STZ as well as AlCl3+d-galactose have impaired spatial and reversal learning with executive functioning, increased brain oxidative and nitrosative stress, cholinergic activity, inflammation and calcium levels. Furthermore, these agents have also enhanced the burden of Aß plaque in the brain. Treatment with 1-phenylisatin and donepezil attenuated i.c.v. STZ as well as AlCl3+d-galactose induced impairment of learning-memory, brain biochemistry and brain damage. Hence, this study concludes that CB2 receptor modulation can be a potential therapeutic target for the management of AD.

Racemose variant of neurocysticercosis: a case report.

Neurocysticercosis is an important parasitic disease of the central nervous system and constitutes a public health challenge for most of the developing world. Radiological findings may be quite variable. A 50 year old man presented with recent onset generalized tonic-clonic seizures. CT scan revealed a lobulated cystic lesion in the right fronto-temporal lobe compressing the lateral and third ventricle and upper brainstem. Clinico-radiological diagnosis of right fronto-temporal space occupying lesion with possibility of cystic glioma was made. He underwent craniotomy with cyst decompression and excision of cyst wall. Histopathology showed features of Racemose variant of Neurocysticercosis. This is an uncommon variant of neurocysticercosis characterized by extraparenchymal involvement, an aggressive clinical course and requiring surgical management. This case is being presented because of its rare occurrence and potential diagnostic difficulties on clinico-radiological grounds.

Primary anetoderma in a young male involving palms, soles and the scalp: rarest of the rare.

Primary anetoderma is a rare idiopathic disease of the skin, characterized by circumscribed areas of loose skin, and loss of elastic fibers upon histopathologic examination. Two forms are traditionally distinguished, primary and secondary. Primary anetoderma occurs when there is no underlying associated skin disease, whereas the latter refers to an abnormal repair mechanism of preexisting skin lesions. We are reporting a case of primary anetoderma with lesions present all over the body, including the scalp, palms and soles, the sites that are not known to be involved in this condition.

Intrapleural streptokinase in multiloculated malignant pleural effusion.

Intrapleural administration of fibrinolytic agents has been shown to be effective and safe in the treatment of loculated parapneumonic effusions. Its use in multiloculated malignant pleural effusions has been rarely reported. We report a case of malignant multiloculated pleural effusion who failed to respond to standard chest tube drainage but showed dramatic and complete resolution with intrapleural streptokinase.

Aggressive pilomatrixoma: a diagnostic dilemma on fine-needle aspiration cytology with review of literature.

We report a case of aggressive pilomatrixoma (PMX) in a 25-year-old male who presented with swelling in left supraclavicular region of 2-month duration. A diagnosis of small round cell tumor was suggested on fine-needle aspiration cytology. He underwent wide excision of the mass. On histomorphological examination, a diagnosis of aggressive PMX was made. The swelling recurred after 3 months of complete resection and on examination had similar morphological features. The case is presented because of the potential diagnostic difficulties on cytological examination and rare occurrence of aggressive variant of PMX.

A study of cervical intraepithelial neoplasia in pregnancy.

OBJECTIVE: To find the incidence of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) in pregnant women and compare Pap smear with the HPV DNA test in detecting HPV infection. MATERIALS AND METHODS: Hundred antenatal women, irrespective of gestational age, were enrolled as subjects in this prospective pilot study for blood investigations, wet mount examination of cervical discharge, Pap smear, and high-risk HPV DNA detection of cervical scrape by PCR. Women showing abnormality in Pap smear and/or those who were high-risk HPV DNA positive were subjected to colposcopy. RESULTS: The incidence of HPV-positive pregnant women was 18 %. Koilocytosis on Pap smear was observed in six women. Three high-risk HPV DNA-positive women showed changes consistent with CIN 1 on colposcopy. CONCLUSIONS: The HPV DNA test is the most sensitive and reliable in detecting HPV infection as compared to Pap smear, but considering the cost of PCR, Pap smear screening of all antenatal women was recommended.

Stromal endometriosis of the intestine: an elusive presentation with a review of the literature: a case report.

Although endometriosis involves the small intestine only rarely, when present, this condition may simulate a variety of inflammatory and sometimes neoplastic conditions because of its nonspecific symptoms. We are reporting here, a case of ileal, caecal and appendiceal endometriosis which presented in the emergency as a case of an acute intestinal obstruction with a long history of symptoms which were referable to the GI tract. The patient had the diffuse involvement of a segment of the ileum with mural thickening and luminal narrowing, which led to obstruction. The literature on small bowel endometriosis has been reviewed and the clinical and pathological features have been discussed.

Types and frequency of preanalytical errors in haematology lab.

AIM: This study was conducted to evaluate the frequency of the preanalytical errors occurring in a haematology laboratory. MATERIAL AND METHODS: A retrospective study was conducted by collecting and analyzing data in duration of one year in the haematology section of the laboratory. Data for all the preanalytical variables according to the predefined categories were scanned. Both IPD and OPD patients were segregated. RESULT: A total of 135808 samples were received in haematology lab during this period, out of which in 1339 samples, preanalytical errors were found, which approximately constituted 1 % of all samples. CONCLUSION: Highest number of samples were rejected due to misidentification, that is 0.35 % and least number were rejected due to dilution of the samples, that is 0.04 %.

Comparison of routine fixation of tissues with rapid tissue fixation.

INTRODUCTION: Conventional formalin-fixed, paraffin-embedded tissue provides superior cellular morphology and long-term storage. Problems with formalin fixation comprise delay of fixation and variations in the duration of fixation. Microwave assisted tissue fixation removes the use of noxious and potentially toxic formalin that decreases the turnaround time and creates a personnel friendly workflow. MATERIAL AND METHODS: The present study was conducted over a period of two years. One hundred and forty paired tissue sections were taken including both neoplastic and non-neoplastic tissues. One of the paired tissues was fixed in formalin and the other was fixed by using microwave irradiation in phosphate buffered saline. Both were then processed by conventional method. Each slide was examined and rated for the adequacy of fixation by two pathologists in a blinded fashion using 7 parameters: Cellular outline, cytoplasmic detail, nuclear detail, erythrocyte integrity, lymphocyte appearance, overall morphology and overall staining. RESULTS: Statistical analysis showed that sections obtained from microwave fixed tissues were comparable to that of routinely fixed tissue. The p-values of all parameters were not significant except for the overall morphology for which p-value was significant owing to loss of tissue in some cases. CONCLUSION: Microwave irradiation substantially shortened the time from specimen reception to diagnosis (turnaround time) and allowed same-day tissue processing and diagnosis of specimens without compromising the overall quality of the histologic section.

Comparative study of processing of haemorrhagic body fluids by using different techniques.

BACKGROUND: Haemorrhagic fluids are samples which are commonly received for cytological examination. The diagnostic efficacy suffers when large numbers of red blood cells are present in the sample. Haemorrhagic fluids are processed by a variety of techniques and the common goal of each technique is selection and concentration of an adequate number of tumour cells with intact cell morphologies, without losing them during processing. AIM: Present study was undertaken to improve the quality of haemorrhagic fluid by using three different haemolysing agents, namely Carnoy's Fixative (CF), saline in Normal Saline Rehydration Technique (NSRT) and Glacial Acetic Acid (GAA) for haemolysis and to find out the most effective processing technique for better cytomorphological assessment. MATERIAL AND METHODS: This study was carried out on 51 haemorrhagic fluids. Processing of haemorrhagic fluid was done by using haemolysing agents, namely CF, GAA and NSRT. After processing fluids with these three techniques, three smears were prepared from each of them, out of which one was air dried and two were wet fixed. Fourth type of smear made without application of haemolysing agent was used as control.The smears were stained with Leishman's stain and wet fixed smears were stained with Hematoxylin and Eosin (H and E) , and Papanicolou's stain (Pap) respectively. RESULTS: NSRT showed lysis of red blood cells (RBCs) in 72.5% of cases, followed by that of CF in 60.8% cases and that of GAA in only 3.9% of cases. Retention of epithelial/mesothelial cells was seen in 70.5% cases with NSRT, followed by that of CF in 57.8% of cases and then by that of GAA in 50.9% of cases. Cytomorphological details were best preserved in CF in 60.6% of cases, followed by GAA in 58.8% of cases and NSRT in 52.9% of cases. CONCLUSION: The most effective method for RBC lysis in smear background and cell retention is NSRT and cytomorphological details are best preserved with CF. But, considering the overall results and procedural simplicity, it was concluded that NSRT was a better technique for processing of haemorrhagic fluid.