A Novel Method for the Early Detection of Single Circulating, Metastatic and Self-Seeding Cancer Cells in Orthotopic Breast Cancer Mouse Models.

BACKGROUND: Metastasis is the main cause of cancer-related deaths, but efficient targeted therapies against metastasis are still missing. Major gaps exist in our understanding of the metastatic cascade, as existing methods cannot combine sensitivity, robustness, and practicality to dissect cancer progression. Addressing this issue requires improved strategies to distinguish early metastatic colonization from metastatic outgrowth. METHODS: Luciferase-labelled MDA-MB-231, MCF7, and 4T1 breast cancer cells were spiked into samples from tumour-naïve mice to establish the limit of detection for disseminated tumour cells. Luciferase-labelled breast cancer cells (±unlabelled cancer-associated fibroblasts; CAFs) were orthotopically implanted in immunocompromised mice. An ex vivo luciferase assay was used to quantify tumour cell dissemination. RESULTS: In vitro luciferase assay confirmed a linear and positive correlation between cancer cell numbers and the bioluminescence detected at single cell level in blood, brain, lung, liver, and mammary fat pad samples. Remarkably, single luciferase-labelled cancer cells were detectable in all of these sites, as the bioluminescence quantified in the analysed samples was substantially higher than background levels. Ex vivo, circulating tumour cells, metastasis, and tumour self-seeding were detected in all samples from animals implanted with highly metastatic luciferase-labelled MDA-MB-231 cells. In turn, detection of poorly metastatic luciferase-labelled MCF7 cells was scarce but significantly enhanced upon co-implantation with CAFs as early as 20 days after the experiment was initiated. CONCLUSIONS: These results demonstrate the feasibility of using an ultrasensitive luciferase-based method to dissect the mechanisms of early metastatic colonization to improving the development of antimetastatic therapies.

Pharmaceutical interventions: A solution to stop smoking.

Background: Smoking has become a worldwide problem and the more problematic is when the youth of any country is highly involved in consuming tobacco that is dangerous for the human being. The Indian youth is involved in smoking-like activities that are dangerous for them. Objectives: To analyze the role of new treatment ways including nicotine gum, nicotine patch, and nicotine replacement therapy backed by pharmaceutical interventions to eliminate smoking from Indian society. Method: The hypotheses of this study are formed on the basis of previous studies and the identification of gap in practices. This study is based on the cross-sectional data that was collected with the help of a questionnaire based on a five-point Likert scale from the Indian pharma industry people. The sample size for this study was 340 with a response rate of 50%. Results: In this study, 179 valid questionnaires were collected back from the respondents, and according to the results, nicotine gum, nicotine patch, and nicotine replacement therapies have a significant (p<0.05) effect on smoker attitudes. Conclusion: This study concludes that pharmaceutical interventions are critical to stopping the smoking habit in Indian society, and this contribution is providing a solution to stop smoking by affecting the smoker's attitude and smoking behavior.

Meckel's diverticulum causing acute intestinal obstruction: A case report and comprehensive review of the literature.

Introduction: Meckel's diverticulum is a congenital anomaly that is often detected incidentally. When it presents symptomatically, it causes painless gastrointestinal bleeding. Nevertheless, in rare instances, it can cause acute intestinal obstruction, often obscuring the true clinical picture. Case presentation: A 31-year-old male presented to the emergency department with a 24-h history of unremitting nausea, biliary emesis, abdominal distension, and absolute constipation. After ruling out the most common etiologies of acute bowel obstruction, radiological imaging was obtained and was suggestive of meckel's diverticulum. Laparoscopic meckel's diverticulectomy was performed, with the subsequent histopathological analysis confirming ectopic gastric tissue. Discussion: Meckel's diverticulum occurs consequent to incomplete obliteration of the vitelline or omphalomesenteric duct, which connects the developing intestines to the yolk sac. It is found in roughly 2% of the population, of which only about 4% may become symptomatic due to any number of complications. Specifically, small bowel obstruction (SBO) and diverticulitis secondary to ectopic gastric or pancreatic tissue are the most common presentations of symptomatic MD. Conclusion: Although relatively rare in adults, MD should be considered in the list of differentials in patients with intussusception leading to SBO, especially on a background history unremarkable for the most common etiologies causing SBO including post-operative adhesions and hernias.

Development of myocarditis and pericarditis after COVID-19 vaccination in adult population: A systematic review.

Objectives: A clear temporal relationship between myocarditis and pericarditis after COVID-19 vaccination has led to the belief that the vaccine may act as a trigger for these cardiologic complications. The aim of this systematic review is to explore the incidence, clinical presentation, management, and association between them. Methods: We conducted a systematic literature search on Cochrane, MEDLINE, and EMBASE as per guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews). A total of 41 case reports and case series describing 97 patients, and 5 original articles describing 15,585,309 participants were selected as part of this review. Results: Of the 97 reported cases describing vaccine-associated myocarditis/pericarditis, 67 (69%) patients received Pfizer-BioNTech and 25 (25.7%) received Moderna. The mean onset of symptoms after vaccine administration was 3.8 ± 4.5 days with three-quarters developing symptoms after the second dose. Chest pain (n = 88, 90%) and fever (n = 33, 34%) were the most common presenting complaints. Out of 97, 80 (82.5%) patients recovered while 4 (4.1%) patients expired. The pooled incidence of myocarditis and pericarditis extrapolated from original studies is 0.001% and 0.0004%, respectively. In the original studies, nearly all the cases of myocarditis and pericarditis were mild. Chest pain and fever were the most common presenting symptoms. Conclusion: Myocarditis and pericarditis after the COVID-19 vaccine have been reported more in young adult males and are most likely to occur after the second dose of mRNA vaccines. The presentation is mild and the majority of the patients recover either completely or partially.

Look, but to the left: A rare case of gallbladder sinistroposition and comprehensive literature review.

Left-sided gallbladder (LSGB) is a rare anatomic variation that, while benign in the context of its transposition, is of significant intraoperative importance. Due to its association with other anatomic anomalies involving key structures in the hepatobiliary system, discovering it intraoperatively as opposed to preoperatively suddenly increases the difficulty of a gallbladder procedure.

Laparoscopy: A Better Approach for Perforated Duodenal Ulcer.

Background Laparoscopic surgery is becoming the gold standard for most abdominal surgeries in recent times. Laparoscopic repair of perforated duodenal ulcer (PDU), however, is still an area of debate. The purpose of this study was to evaluate the safety and efficacy of laparoscopic repair of PDU versus open repair. Methods In this cross-sectional study, patients were consecutively sampled. Out of 101 patients with clinically diagnosed PDU, 36 patients underwent laparoscopic Graham patch repair and 65 underwent open Graham patch repair in a tertiary care academic hospital. Open repair was via upper midline incision, and laparoscopic repair by the three-port technique. The following stages were calculated: operative time, duration of postoperative analgesia, time taken to mobilize, and patient length of stay after the operation. Results The mean operative time was somewhat longer in the laparoscopy group compared to the open repair group (74.01 vs 56.17 minutes, respectively). Mean postoperative analgesia requirement, time taken to mobilize, and hospital stay were significantly shorter after laparoscopy than after open repair (1.21 days, 9.32 hours, and 3.12 days vs 3.83 days, 16.20 hours, and 4.85 days, respectively). Three patients (8%) in the laparoscopy group and 35 (54%) in the open repair group had postoperative complications. Conclusions Laparoscopic repair of PDU is a safe approach and better than open repair in terms of operative time with the right level of expertise only, postoperative analgesia requirement, mobilization, duration of hospital stay, and incidence of postoperative respiratory and wound complications.

Clinical and Pathological Characteristics of Soft Tissue Sarcomas: A Retrospective Study From a Developing Country.

Introduction Soft tissue sarcomas remain an exceedingly rare malignancy. While soft tissue sarcomas boast a high mortality rate, their characteristics and behavior patterns are poorly understood. This study aims to evaluate the various aspects that pertain to soft tissue sarcomas, including their histology, tumor characteristics, survival rates, and therapeutic modalities. Methods A retrospective study analyzing the data from 19 patients presenting over four years with a histologically confirmed diagnosis of soft tissue sarcomas was conducted. The patients were studied for various parameters, including tumor site and the particular pathological subtypes. The data obtained were analyzed using the SPSS 23.0 statistical software (IBM Corporation, Armonk, NY), and the results were then tabulated. Results A total of 19 patients with a confirmed diagnosis of a soft tissue sarcoma were included in the study. The mean age of the patients included was 45.32 ± 16.88 years. Wide local excision was the most common surgical procedure employed for the resection of these tumors. Within the cohort, the mortality rate was noted to hover at 10.52%. Gastrointestinal stromal tumors were observed in 21% of the patients and were therefore the most common histological subtype. Of the patients included, 42.10% required blood transfusion during the perioperative time. Most of the tumors were noted to be intermediate grade, with high-grade tumors observed in 26.3% of the cases. Conclusion Soft tissue sarcomas remain a rare but potent cause of death in developing countries. The diversity of the tissues that they afflict renders their prompt detection a diagnostic challenge. A meticulous exploration of the various characteristics honed by soft tissue sarcomas, such as the particular histological subtype and the associated mortality rates, can better elucidate the prognosis and the eventual disease outcomes.

Early Postoperative Outcomes of Breast Cancer Surgery in a Developing Country.

Background Breast cancer remains the most common cause of cancer related mortality amongst women in Pakistan. Postoperative complications can demoralize the patients and potentially delay adjuvant treatment, leading to adverse outcomes. The overarching aim of the study is to delineate the early postoperative outcomes of breast cancer surgery in Pakistan. Materials and Methods A retrospective study involving patients who underwent breast cancer surgery from June 2016 to December 2019 was conducted. Perioperative morbidities (30 days) were evaluated and documented. The results obtained were analyzed using the SPSS 23 software (IBM Corporation, Armonk, NY). Results A total of 94 patients were included in the study, with the mean age of 50±12.8 years. Breast conserving surgery was performed in 32% (n=31) of the patients, while the remaining 68% (n=63) underwent modified radical mastectomy. The most common complications were seroma formation, flap necrosis and hematoma formation and were observed in 5.3% (n=5), 4.3% (n=4) and 3.2% (n=3) of the patients, respectively. Conclusion Early postoperative complications can delay the commencement of adjuvant systemic therapy required for further management of breast cancer. These complications elicit equally grave consequences for patients undergoing breast conserving surgery and modified radical mastectomy.

The Spectrum of Gallbladder Histopathology at a Tertiary Hospital in a Developing Country: A Retrospective Study.

Background Affections of the gallbladder remain exceedingly ubiquitous and often warrant surgical intervention. The histopathological patterns represent a spectrum, ranging from cholecystitis to gallbladder carcinoma. The present study aims to delineate the occurrence of various gallbladder histopathologies in a tertiary care hospital in Pakistan. Methods A retrospective study was conducted at Maroof International Hospital, Islamabad, Pakistan. Histopathological records of 442 gallbladder specimens obtained from cholecystectomy were analysed. The prevalence of various histopathological outcomes was assessed. The data were eventually analysed using the SPSS 23.0 software (Armonk, NY: IBM Corp.). Thereafter, the distribution of various gallbladder histopathologies was tabulated across gender.  Results Of the 442 patients included, 330 were females and 112 were males, with the mean age hovering at 45.77±14.65 years. The most common histopathological findings were chronic cholecystitis and cholesterolosis, observed in 78.6% and 32.8% of the patients, respectively. While only one case of gallbladder adenocarcinoma was observed, multiple specimens divulged premalignant lesions including reactive atypia and intestinal metaplasia. Conclusions Diseases of the gallbladder often mandate prompt surgical intervention. Of these, chronic cholecystitis, which is an established risk factor for gallbladder carcinoma, is exceedingly common. The employment of histopathological techniques remains imperative in the detection of premalignant and malignant lesions that might otherwise evade macroscopic detection and thus progress to adenocarcinoma.