Long-term clinical outcomes of male breast cancer patients treated with curative intent by trimodality therapy at an academic university hospital in India.

INTRODUCTION: Male breast cancer is rare and accounts for less than 1% of all breast cancer cases worldwide. METHODS: This retrospective cohort study included all patients of invasive male breast cancer treated with curative intent by a trimodality approach via a multidisciplinary team at an academic university hospital in India between 2009 and 2023. Records were identified from a prospectively maintained database. Clinicopathological parameters, treatment details and survival were recorded and analysed. RESULTS: Thirty-four patients were included. The median (IQR) age was 55(44-63) years. Most patients were overall stage III (74%) and node positive (79%) with Scarff-Bloom-Richardson grade II (50%). Twenty-five patients (73%) were oestrogen receptor (ER) positive. Lymphovascular space invasion (LVSI) and perineural invasion (PNI) were present in 62% and 21% of patients, respectively. The most common chemotherapy timing was adjuvant (53%) followed by neoadjuvant (41%), and the most commonly used regimen consisted of a combination of doxorubicin-cyclophosphamide followed by a taxane (53%). Most (85%) patients underwent a mastectomy, five patients underwent breast conservation. All patients received radiotherapy to a dose of 42.6 Gy in 16 fractions, followed by a tumour bed boost for those undergoing breast conservation. At a median follow-up of 70 months (range 10-159 months), the five and ten-year overall survival was 91% and 58%, and the five-year disease-free survival (DFS) was 67%. The median DFS was 72 months. On univariate analysis, the tumour sub-type (Luminal versus TNBC) significantly predicted DFS (P = 0.03 log-rank). CONCLUSION: Breast cancer in males has a high incidence of node positivity, ER positivity and LVSI. Even with advanced stages at presentation, trimodality therapy in a multidisciplinary setting offers good long-term outcomes.

Treatment Outcomes of Incidental Gallbladder Cancer - Results from a High-Volume Tertiary Care Centre in North India.

Gallbladder cancer (GBC) is a lethal disease. Incidentally detected gallbladder cancer (IGBC) presents a unique opportunity for early management and better outcomes. We present the institutional experience of a high-volume tertiary care center in northern India. Retrospective analysis of a prospectively maintained database was performed and data of all IGBC patients between January 2014 to December 2021 was analyzed. There were 125 patients of IGBC among the 750 patients of GBC seen during the study period. Of these 125 patients, 72 (57.6%) patients were not eligible for surgery. Successful completion radical cholecystectomy (CRC) was possible in 37 (69.8%) of the 53 patients who underwent surgery. On univariate analysis, thickness of gallbladder wall 10 mm or more (p < 0.001, OR 19.0, 95% CI 4.58-78.76), pathological stage (p < 0.001, OR 5.8, 95% CI 2.45-14.98) and median delay of 16 weeks or more (p < 0.001, OR 17.0, 95% CI = 4.08-70.76), were associated with inoperability. However, on multivariate analysis only gallbladder wall thickness of 10 mm or more (p < 0.001, AOR 17.9, 95% CI 3.24-98.78) and median delay of 16 weeks or more (p < 0.001, AOR 32.33, 95% CI 6.05-172.66) remained significant. Median time to recurrence (TTR) and overall survival (OS) was not reached after a median follow up of 30 months in patients undergoing successful CRC. Successful outcomes of IGBC are dependent on several factors. Diligent workup of suspicious thickening before simple cholecystectomy for gallstone disease and timely referral of IGBC to tertiary care are the keystones for good outcomes.

Cancer stem cell biomarkers SOX2 and Oct4 in cervical cancer patients undergoing chemoradiotherapy.

BACKGROUND: Cancer stem cell biomarkers SRY (sex-determining region Y)-box 2 (SOX2) and octamer-binding transcription factor 4 (Oct4) account for radioresistance in cervical squamous cell cancers (CSCCs). Their clinical implications are limited and contradictory. METHODS: In this prospective cohort study, we recruited patients with FIGO IB2-IVA CSCC treated with primary chemoradiotherapy on regular follow-up. Tissue biopsy specimens were evaluated for SOX2 and Oct4 expression by immunohistochemistry, quantified by a product of proportion and intensity scores. RESULTS: A total of 59 patients were included. Most had a moderately differentiated (81%), keratinizing (59%) CSCC, and ≥FIGO stage IIB disease (95%). SOX2 expression (high:low 21:38 patients) and Oct4 expression (high:low 4:55 patients) had a significant interrelation (p = 0.005, odds ratio (95% CI) - 1.23 (1.004-1.520)). At a median follow-up of 36 months, the 3-year overall survival (OS) was 60% and 53% for low and high SOX2 expression (p = 0.856), and 54% and 100% for low and high Oct4 expression (p = 0.114). The 3-year disease-frese survival (DFS) was 65% and 50% in the low and high SOX2 expression (p = 0.259), and 59% and 75% for low and high Oct4 expression (p = 0.598). SOX2 expression was the only variable significantly associated with a lower OS and DFS on regression analysis. CONCLUSION: Our study demonstrated a trend toward improved OS and DFS with low SOX2 and high Oct4 expression in CSCC patients undergoing chemoradiotherapy.

Efficacy of decentralised home-based antihypertensive treatment in older adults with multimorbidity and polypharmacy (ATEMPT): an open-label randomised controlled pilot trial.

BACKGROUND: Older patients with multimorbidity and polypharmacy have been under-represented in clinical trials. We aimed to assess the effect of different intensities of antihypertensive treatment on changes in blood pressure, major safety outcomes, and patient-reported outcomes in this population. METHODS: ATEMPT was a decentralised, two-armed, parallel-group, open-label randomised controlled pilot trial conducted in the Thames Valley area, South East England. Individuals aged 65 years or older with multimorbidity (three or more chronic conditions) or polypharmacy (five or more types of medications) and a systolic blood pressure of 115-165 mm Hg were eligible for inclusion. Participants were identified through a search of national hospital discharge databases, identification of patients registered with an online pharmacy, and via targeted advertising on social media platforms. Participants were randomly assigned to receive up to two more classes versus up to two fewer classes of antihypertensive medications. Apart from routine home visits for conducting the baseline assessment, all communication, monitoring, and management of participants by the trial team was conducted remotely. The primary outcome was change in home-measured blood pressure. FINDINGS: Between Dec 15, 2020, and Aug 31, 2022, 230 participants were randomly assigned (n=126 to more vs n=104 to fewer antihypertensive medications). The frequency of serious adverse events was similar across both groups; no cardiovascular events occurred in the more antihypertensive drugs group, compared with six in the fewer antihypertensive drugs group, of which two were fatal. Over a 13-month follow-up period, the mean systolic blood pressure in the group allocated to receive more antihypertensive medications decreased from 134·5 mm Hg (SD 10·7) at baseline to 122·1 mm Hg (10·5). By contrast, in the group allocated to receive fewer antihypertensive medications, it remained relatively unchanged, moving from 134·8 mm Hg (SD 11·2) at baseline to 132·9 mm Hg (15·3); this corresponded to a mean difference of -10·7 mm Hg (95% CI -17·5 to -4·0). INTERPRETATION: Remotely delivered antihypertensive treatment substantially reduced systolic blood pressure in older adults who are often less represented in trials, with no increase in the risk of serious adverse events. The results of this trial will inform a larger clinical trial focusing on assessing major cardiovascular events, safety, physical functioning, and cognitive function that is currently in the planning stages. These results also underscore the efficiency of decentralised trial designs, which might be of broader interest in other settings. FUNDING: National Institute for Health Research Oxford Biomedical Research Centre and the Oxford Martin School.

Uniportal video-assisted thoracoscopic surgery in semi-prone position utilising direct endobronchial intubation for oesophagus leiomyoma excision.

Leiomyomas are the most common benign tumours of oesophageal smooth muscle origin. In this era of constantly evolving medical technology, video-assisted, robot-assisted and endoscopic approaches are the minimally invasive strategies for the excision of these lesions. Here, we report our modification of this surgery. The lesion was excised with uniportal video-assisted thoracoscopic surgery in a semi-prone position with single-lumen endobronchial intubation.

Quality of Life in Patients with Recurrent Oral Squamous Cell Carcinoma: A Study from India.

Background: Locoregional recurrence of oral cancer causes significant morbidity. This study aims at assessing the functional outcomes of patients undergoing treatment for recurrent oral squamous cell carcinoma. Methods: This study was done in a tertiary care center in North India and includes prospective cohort of 179 recurrent oral carcinoma patients, from September 2017 to September 2018. Patients undergoing treatment of recurrent oral carcinoma were assessed for quality-of-life score at baseline before starting treatment and two months after the completion of the treatment. For the assessment, EORTC QLQH&N35 questionnaire was used. Results: Of 179 patients included, 71 (39.66%) patients underwent salvage surgery and 104 patients (58.10%) received palliative chemotherapy. One hundred and thirty patients could complete the "EORTC-QOL-H&N-35" questionnaire on required two occasions. Forty-nine patients died before completing second questionnaire. More than half (55.6%) of patients who underwent salvage surgery had improved quality of life after the procedures. They have little or no pain in oral cavity, improved swallowing, less odynophagia, improvement in neck and shoulder pain, less problems with the external appearance and socialization, and enjoyed better sexual life. In patients receiving palliative chemotherapy, the quality of life declined in majority (88.1%) of the patients. Conclusions: Although salvage surgery is the best modality of treatment for recurrent oral carcinoma, only about one-third of patients qualify for surgery and enjoy improved quality of life following surgery. On the other hand, in majority of the patients receiving palliative chemotherapy, the quality of life worsened with time and treatment.

SPIONs Conjugate Supported Anticancer Drug Doxorubicin's Delivery: Current Status, Challenges, and Prospects.

Considerable efforts have been directed towards development of nano-structured carriers to overcome the limitations of anticancer drug, doxorubicin's, delivery to various cancer sites. The drug's severe toxicity to cardio and hepatic systems, low therapeutic outcomes, inappropriate dose-demands, metastatic and general resistance, together with non-selectivity of the drug have led to the development of superparamagnetic iron oxide nanoparticles (SPIONs)-based drug delivery modules. Nano-scale polymeric co-encapsulation of the drug, doxorubicin, with SPIONs, the SPIONs surface end-groups' cappings with small molecular entities, as well as structural modifications of the SPIONs' surface-located functional end-groups, to attach the doxorubicin, have been achieved through chemical bonding by conjugation and cross-linking of natural and synthetic polymers, attachments of SPIONs made directly to the non-polymeric entities, and attachments made through mediation of molecular-spacer as well as non-spacer mediated attachments of several types of chemical entities, together with the physico-chemical bondings of the moieties, e.g., peptides, proteins, antibodies, antigens, aptamers, glycoproteins, and enzymes, etc. to the SPIONs which are capable of targeting multiple kinds of cancerous sites, have provided stable and functional SPIONs-based nano-carriers suitable for the systemic, and in vitro deliveries, together with being suitable for other biomedical/biotechnical applications. Together with the SPIONs inherent properties, and ability to respond to magnetic resonance, fluorescence-directed, dual-module, and molecular-level tumor imaging; as well as multi-modular cancer cell targeting; magnetic-field-inducible drug-elution capacity, and the SPIONs' magnetometry-led feasibility to reach cancer action sites have made sensing, imaging, and drug and other payloads deliveries to cancerous sites for cancer treatment a viable option. Innovations in the preparation of SPIONs-based delivery modules, as biocompatible carriers; development of delivery route modalities; approaches to enhancing their drug delivery-cum-bioavailability have explicitly established the SPIONs' versatility for oncological theranostics and imaging. The current review outlines the development of various SPIONs-based nano-carriers for targeted doxorubicin delivery to different cancer sites through multiple methods, modalities, and materials, wherein high-potential nano-structured platforms have been conceptualized, developed, and tested for, both, in vivo and in vitro conditions. The current state of the knowledge in this arena have provided definite dose-control, site-specificity, stability, transport feasibility, and effective onsite drug de-loading, however, with certain limitations, and these shortcomings have opened the field for further advancements by identifying the bottlenecks, suggestive and plausible remediation, as well as more clear directions for future development.

Malignant Eccrine Spiroadenoma of Right Temporal region: Reporting of a Rare Case.

Eccrine spiroadenoma arises from adnexal tissue of skin and is usually benign, slow growing and may remain static for decades [1]. Dabska et al. first defined the term malignant eccrine spiroadenoma (MES) in 1972, since then around 100 cases of MES have been found (Alejandra de Andrés Gómez. Malignant eccrine breast spiroadenoma. A case report and literature review [2]). Its very rare kind of tumor can arise either from transformation in benign lesion or can arise de novo. Here we are reporting a case of malignant spiroadenoma arising from transformation of benign lesion, its pathology and treatment.

Guided Needle Aspirations of Intra-Abdominal Masses: Analogy between Liquid-Based and Conventional Smear Preparation Methods.

OBJECTIVE: Image-guided fine needle aspiration cytology with conventional smear (CS) preparation offers onsite cellular adequacy evaluation; however, it still provides false negatives due to faulty smear preparations. Liquid-based cytology (LBC) can be advantageous in these scenarios. Hence, with an aim to investigate utility of LBC in these samples, we carried out the above study with objectives to find diagnostic accuracy of LBC and agreement of LBC with CS methods in guided aspiration samples from intra-abdominal masses. METHODS: A prospective observational study, of 113 patients with clinical or radiological diagnosis of intra-abdominal masses, was carried out. SurePath BD™ was used for LBC smear preparation, and the standard protocol was used for CS preparation. RESULTS: LBC alone was diagnostic in 80.8% of the cases, and CS alone was diagnostic in 71.2% cases (agreement was 83.7%, p = 0.03). Cellular morphology was better preserved in LBC; however, interpretation was easier in CS. CONCLUSION: CS may be complimented with LBC sample collection method to enhance the sensitivity of intra-abdominal FNA.

Radical surgery for de novo gallbladder carcinoma-Single-center analysis of prognostic factors and survival outcomes from an endemic region.

BACKGROUND AND OBJECTIVE: Gallbladder cancer (GBC) is an aggressive malignancy where curative resection is possible in few and survival is poor. There are limited data on outcomes in patients with de novo GBC from endemic regions undergoing surgery for curative intent. We report survival outcomes in this group of patients from a region with high incidence of disease. METHODS: We reviewed the records of all GBC patients (2014-2018) and included those who underwent radical cholecystectomy (RC) for de novo GBC. Univariable and multivariable analyses were performed to identify factors influencing recurrence and survival. RESULTS: A total of 649 patients with GBC were evaluated for surgery and curative intent surgery was attempted in 246 (38%) patients. Of these 246 patients, RC was performed in 115 patients, with histologically confirmed de novo GBC. Locally advanced disease (≥stage IIIB) was present in 52 (45.2%) patients. Median time to recurrence and overall survival (OS) were 31 and 36 months, respectively. Lymph node positivity (p = 0.005) and grade significantly influenced OS on multivariable analysis. CONCLUSION: Satisfactory survival outcomes are possible after RC for de novo GBC. Extended resections performed in high volume centers combined with appropriate adjuvant treatment can offer significant survival benefits, with acceptable morbidity and mortality rates.

Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach.

OBJECTIVE: In this study, small molecules possessing tetrahydropyrimidine derivatives have been synthesized having halogenated benzyl derivatives and carboxylate linkage. As previously reported, FDA approved halogenated pyrimidine derivatives prompted us to synthesize novel compounds in order to evaluate their biological potential. METHODOLOGY: Eight pyrimidine derivatives have been synthesized from ethyl acetoacetate, secondary amine, aromatic benzaldehyde by adding catalytic amount of CuCl2·2H2O via solvent less Grindstone multicomponent reagent method. Molecular structure reactivity and virtual screening were performed to check their biological efficacy as an anti-oxidant, anti-cancer and anti-diabetic agent. These studies were supported by in vitro analysis and QSAR studies. RESULTS: After combined experimental and virtual screening 5c, 5g and 5e could serve as lead compounds, having low IC50 and high binding affinity.

Surgical outcomes in oral cancer involving the central arch of the mandible in elderly patients: An institutional experience.

BACKGROUNDS: Oral squamous cell cancer (SCC) is one of the most common cancers. The most common age of presentation is fifth to sixth decade. Management of this disease is dictated by stage, age, and related comorbidities. Elderly patients have their own set of limitations as far as their management is concerned. Carcinoma involving central mandibular arch is a challenging disease for surgeons, especially in the elderly. This article describes our experience with the surgical treatment of oral cancer involving the central arch of the mandible in elderly patients. METHODS: Forty elderly (≥60 years) patients with histologically proven SCC of the oral cavity in which disease was involving the central arch of the mandible, were included in our study. Demographic, clinical, and treatment-related factors were recorded. The outcome was assessed in terms of postoperative complications, recurrence, and patient survival. RESULTS: The median age of the patients was 63 years. The male:female ratio was 7:3. A history of oral tobacco use was present in 95% of patients. The most common site of disease was lower alveolus (80%) followed by carcinoma of the lower lip (20%). Majority of our patients (77.3% [30]) were having Stage IV disease. Mandibulectomy was either segmental (62.5%) or marginal (37.5%). Bilateral neck dissection (37/40, 92.5%) was done in most patients. Among all patients, 62.5% (25) received adjuvant radiotherapy. The local recurrence rate after a median follow-up of 30 months was 15% (6). Two-year disease-free survival and overall survival were 89% and 90%, respectively. CONCLUSION: Central arch of the mandible is a difficult disease to treat. It needs a complex and lengthy reconstructive procedure. Comorbidities such as extreme age, diabetes, and pulmonary and cardiac illnesses make it more challenging to manage. With the proper evaluation of comorbidities and avoiding long, cumbersome procedures, we can provide patients a fairly good chance of survival.

Continuing cancer surgery through the first six months of the COVID-19 pandemic at an academic university hospital in India: A lower-middle-income country experience.

BACKGROUND: The novel coronavirus pandemic (COVID-19) hinders the treatment of non-COVID illnesses like cancer, which may be pronounced in lower-middle-income countries. METHODS: This retrospective cohort study audited the performance of a tertiary care surgical oncology department at an academic hospital in India during the first six months of the pandemic. Difficulties faced by patients, COVID-19-related incidents (preventable cases of hospital transmission), and modifications in practice were recorded. RESULTS: From April to September 2020, outpatient consultations, inpatient admissions, and chemotherapy unit functioning reduced by 62%, 58%, and 56%, respectively, compared to the same period the previous year. Major surgeries dropped by 31% with a decrease across all sites, but an increase in head and neck cancers (p = .012, absolute difference 8%, 95% confidence interval [CI]: 1.75% - 14.12%). Postoperative complications were similar (p = .593, 95% CI: -2.61% - 4.87%). Inability to keep a surgical appointment was primarily due to apprehension of infection (52%) or arranging finances (49%). Two COVID-19-related incidents resulted in infecting 27 persons. Fifteen instances of possible COVID-19-related mishaps were averted. CONCLUSIONS: We observed a decrease in the operations of the department without any adverse impact in postoperative outcomes. While challenging, treating cancer adequately during COVID-19 can be accomplished by adequate screening and testing, and religiously following the prevention guidelines.