Histopathological Variables Research Articles

Clinico-histopathological review of cutaneous sarcoidosis: A retrospective descriptive study.

Background Sarcoidosis is a systemic, non-caseating granulomatous disease characterised by clinical and histopathological variability. Objective To review cases of cutaneous sarcoidosis and describe their clinical and histopathological features. Methods A retrospective study was conducted to analyse the clinical and histopathological frecords of all available skin biopsy slides signed out as 'sarcoidal tissue reaction' or 'sarcoidosis' from 2014 till 2022. Results A total of 25 cases were studied. The lesions were most commonly located on the head and neck (18 cases, 72%). Morphologically plaques (20%) were the most common, and the majority of cases had lesions of ≥2 distinct morphologies (44%). Histologically, classical naked granulomas were observed in 72% of cases. The granulomatous infiltrate was pandermal in 56% of cases, perivascular and interstitial in 16%, and perivascular, perieccrine, and interstitial in 12%. Granulomas with a 'leprosy' pattern were observed in 20% of cases. High-density granulomas (occupying >30% of the dermis) were present in 64% of cases. Fibrinoid necrosis and fibrosis between granulomas were observed in 16% and 8% cases, respectively. Inclusion bodies, such as asteroid and Schaumann bodies, were seen in 24% and 4% cases, respectively. Reticulin-rich granulomas were observed in 54% cases, while reticulin-poor granulomas were seen in 8.3%. Elevated serum ACE levels were found in 14 cases, and tuberculin skin test, conducted in 22 cases, was negative. Extracutaneous involvement was found in 11 cases, with 10 having pulmonary and 1 with pulmonary and splenic involvement. Limitation Retrospective nature of the study and small sample size. Conclusion Cutaneous sarcoidosis presents with a wide range of clinical and histomorphological features, necessitating clinico-histopathological correlation and ancillary investigations to establish the diagnosis and rule out mimickers.

Biopsy Proven IgA Nephropathy in Children: A Single Center Experience

Introduction: IgA nephropathy is one of the most common primary glomerulonephritis in children and adolescents worldwide. IgA nephropathy is present with symptoms ranging from recurrent asymptomatic hematuria to gross hematuria, nephrotic syndrome and rapid decline in renal function. MEST-C scoring system identified various histopathological variables. Objectives: Aim of this study was to find out the presentation at time of diagnosis of IgA nephropathy and determine the histopathological finding with crescent according to the Oxford classification of IgA nephropathy. Methods: This was a cross-sectional study conducted in Kanti Children’s Hospital from 2012 to 2023. All 28 children below 14 years of age diagnosed with biopsy proven IgA nephropathy were included in the study. Henoch schonlein purpura and systemic lupus erythematosus were excluded from the study. Demographic information, such as age, gender, mode of presentation, and histological findings were recorded. Result: A total 28 children were analyzed with male preponderances 16 (57.1%). IgA nephropathy was more common in age group 11 to 14 years. Among children with IgA nephropathy 21 (75%) had gross hematuria and 14 children had hypertension (50%). According to MEST classification maximum number of children had E1 and T2, 22 (78.57%) and 21 (75%) respectively. Crescent was found in 17 (60.71%) cases. Conclusion: Children with IgA nephropathy gross hematuria is most common presentation and crescents are also common in renal biopsies.

Effect of the COVID-19 Pandemic on the Management of Breast Cancer Patients.

Background: The COVID-19 pandemic has significantly affected breast cancer patients by causing delays in diagnosis and treatment processes. This study aims to investigate the effects of the pandemic on the treatment process and short-term outcomes of breast cancer patients. Methods: This retrospective, cross-sectional, single-center study included 414 patients who underwent surgery for breast cancer at the Inonu University General Surgery Clinic between March 2018 and June 2021. The patients were divided into two groups: pre-pandemic (Pre-COVID-19; n = 240) and pandemic (COVID-19 Era; n = 174) periods. The groups were compared in terms of demographic, clinical, and histopathological variables. Results: During the pandemic period, the use of neoadjuvant therapy (from 21.3% to 34.5%) and preoperative PET-CT imaging (from 80.4% to 90.8%) rates increased, while breast-conserving surgery (from 27.9% to 19.0%) and the presence of comorbid diseases (from 45.0% to 29.9%) decreased significantly. While there was no significant difference between the groups in terms of the time from diagnosis to surgery (25 vs. 28.5 days, p = 0.121), the time to report the pathology result after surgery decreased during the pandemic period (28 vs. 23 days, p < 0.001). There was no significant difference between the groups in terms of immunohistochemical (ER, PR, Ki-67, E-cadherin, and c-erbB2), histopathological (lymphovascular invasion, perineural invasion, comedo necrosis, modified Bloom-Richardson grade, and TNM classification), and clinical (recurrence, metastasis, and axillary lymph node metastasis) features of the tumor. The mortality rate in the Pre-COVID-19 group (7.1%) was significantly higher than in the COVID-19 Era group (2.3%) (p = 0.049). Finally, in terms of the survival analysis, a statistically significant difference was found between the Pre-COVID-19 and COVID-19 Era groups in terms of the mean follow-up duration of the patients (p = 0.044). Conclusions: The study results show that the use of neoadjuvant therapy and radical surgery preference increased in breast cancer treatment during the pandemic period, but there was no significant change in tumor biology and histopathological features. Breast-conserving surgery rates, comorbidity rates, and pathology reporting times were significantly shortened. Long-term follow-up periods of 3 and 5 years are needed to see the impact of the pandemic on breast cancer patients.

Predictive Factors of Athyroglobulinemia After Total Thyroidectomy for Papillary Thyroid Cancer.

Background: Thyroglobulin (Tg) is the specific tumor marker for epithelial thyroid cancer. It holds significant value in the postoperative period, and somehow, the goal of surgery in papillary thyroid cancer (PTC) undergoing total thyroidectomy is to achieve undetectable levels of postoperative thyroglobulin (uTg). Methods: This is a retrospective single-center study in which first basal Tg values were evaluated post-surgery in PTC patients undergoing total thyroidectomy. Patients with elevated antithyroglobulin antibodies were excluded. The impact of various demographic, clinical, therapeutic, tumor-stage related, and histopathological variables on the achievement of undetectable thyroglobulin levels (uTg, <1 ng/mL) was studied. A descriptive and logistic regression-based bivariate and multivariate analysis was planned using STATA vs. 16.1. program. The significance level was stated at 0.05. Results: Basal athyroglobulinemia was obtained in 89.6% of 202 patients operated on between January 2015 and June 2023 in a single referral institution. Due to the limited number of cases with detectable Tg, multivariate analysis could not be performed. The main factors that favored its achievement on bivariate analysis were a smaller tumor size (p = 0.003), no need for extended resections due to local invasion beyond the thyroid gland (p = 0.003) or neck dissection (p = 0.039), absence of distant metastases (p = 0.000), and a lower MACIS score (p < 0.000). Conclusions: The achievement of uTg was closely related to factors related to tumor stage (tumor diameter, lymph node spread, and metastatic disease), and it was not influenced by differences in epidemiological data, clinic manifestations, preoperative diagnosis, multifocality, or the presence of aggressive cytological variants.

Role of Verhoeff’s Elastic Stain to Detect Venous Invasion in Colorectal Adenocarcinoma

Background: Venous invasion is not only an important prognostic indicator in colorectal cancer, but also an important factor of deciding treatment plan for adjuvant therapy. Vascular invasion is usually assessed using hematoxylin and eosin (H &amp; E). But the accuracy of detection of venous invasion using H &amp; E is debatable. Verhoeff's elastic stain is a staining protocol used to demonstrate normal or pathologic elastic fibers, which can be used to improve the detection of venous invasion. Objectives: To evaluate the role of Verhoeff’s elastic stain to detect venous invasion in colorectal adenocarcinoma. Methods: This was a cross-sectional study carried out among 91 cases of colorectal adenocarcinoma. The duration for this study was from March, 2020 to February, 2022. Demographic and histopathological variables were assessed. Venous invasion with both H&amp; E and Verhoeff’s stains were evaluated. Results: Mean age was 51.7 ± 10.9 years. The majority of the patients were males (61.5%). The most common site of the tumor was colon (74.7%). Tumors having size ≥5 cm in diameter (71.4%) were more common. Majority (78.0%) were found to be moderately differentiated neoplasm by histological grading. The rate of venous invasion detection was higher with Verhoeff’s elastic stain compared to H &amp; E stain. Positive results for venous invasion were observed in 21 (23.1%) and 40 (44.0%) cases stained with H &amp; E and Verhoeff’s elastic stain, respectively. Conclusion: This study found that Verhoeff's elastic stain is better at detecting venous invasion in colorectal adenocarcinoma than H&amp;E stain. Therefore, Verhoeff's elastic stain can be routinely employed to detect venous invasion in resected samples of colorectal carcinoma.

Immunohistochemical Expression of Mismatch Repair Proteins in Colorectal Carcinomas with Histopathological Correlation in a Quaternary Care Centre in South India

Background and Aims: Colorectal carcinomas are one of the most prevalent malignant neoplasms globally and are characterised by a range of genetic and epigenetic alterations, primarily chromosomal instability and microsatellite instability. This study aims to assess the expression of MMR proteins in patients with colorectal carcinoma and to examine the relationship between MMR status and various histopathological and clinical variables. Material and Methods: All biopsy and resection cases of colorectal carcinoma on which MMR was done by IHC were studied from December 2022 to November 2023. Histopathological and immunohistochemical assessments of mismatch repair proteins were done for 153 colorectal carcinoma patients in formalin-fixed paraffin-embedded tumour tissues. Statistical analysis was carried out using SPSS software (IBM, 28.0). Results: Out of 153 cases collected, 23 cases (15%) had a loss of MMR expression, and 130 cases (85%) had no loss of MMR protein. Combined loss of MLH1 and PMS2 was found in 16 cases (70%), combined loss of MSH2 and MSH6 was found in five cases (21%) and isolated loss of PMS2 was found in two cases (9%). Adenocarcinoma NOS, mucinous differentiation, medullary pattern, right-sided tumours, female gender and younger age group correlated with loss of MMR expression. Conclusion: Molecular study is the first approach for detecting MSI associated with CRC, IHC is a very good alternative to identify microsatellite instability. IHC methods can be used as a reliable tool in the workup for MSI as IHC markers (antibodies to the MMR proteins) are now easily accessible in most laboratories.

Multidimensional assessment of the learning curve of intracorporeal anastomosis during laparoscopic right colectomy.

After resection during a laparoscopic right colectomy (LRC), reconstruction can be conducted with an intracorporeal (IA) or extracorporeal anastomosis. Although IA benefits are well documented, its implementation has been slow due to a steep learning curve (LC) mainly associated with intracorporeal suturing. The aim of this study is to assess the LC of IA in LRC. Consecutive patients undergoing a LRC with IA between January 2016 and June 2023 were included. Clinical, perioperative, and histopathological variables were collected. Correlation and cumulative sum (CUSUM) analyses between the operating time and case number were performed. 'Surgical success' as a composite outcome was also analysed by performing a CUSUM plot. Completion LC case number was determined based on these analyses. Pre-LC and post-LC perioperative outcomes were compared. Two-hundred-and-ninety patients underwent a LRC during the study period. Sixty-seven met inclusion criteria. Correlation analysis identified a significant operating time reduction with increasing case numbers (p = 0.034). Total complications during implementation period were 25,3%, with 6% of severe complications. Operative time CUSUM analysis identified a consistent downwards trend after case 36 and surgical success CUSUM analysis after case 37. Two phases were established: pre-LC (case 0-37th) and post-LC (38th-67). Pre-LC and post-LC revealed a significant decrease in operative time (187vs177.8min;p = 0.016), and length of stay (4vs3 days;p < 0.001). No difference between overall complications, severe complication, or reoperation rates were detected. The LC of laparoscopic IA can be achieved after 37 cases in centres with experience in advanced laparoscopic surgery. Further studies will be required to confirm these results.

Factors Influencing Endoscopic Dacryocystorhinostomy Outcomes: A Comprehensive Clinical and Histopathological Analysis and Review of the Literature.

The main challenge in maintaining long-term success of endoscopic dacryocystorhinostomy is preventing fibrosis and scarring at the anastomosis site. Despite numerous studies on surgical techniques, research on histological factors linked to postoperative scarring is limited. This study evaluated long-term (range, 12-18 months) outcomes and systematically examined clinical and histopathological factors that may contribute to restenosis. This retrospective study included 47 patients who underwent a unilateral surgery intervention for primary acquired lacrimal duct obstruction. The following clinical and histopathological variables were considered to assess the risk factors for the development of restenosis: sex, age, duration of disease, clinical manifestation of disease, clinical features of the lacrimal sac perceived intraoperatively, fibrosis, and mononuclear cell infiltrates. Statistical analysis showed that only patient sex (Pearson's chi-squared test, p = 0.007) and severity of intraoperative adhesions in the lacrimal sac (Pearson's chi-square test, p = 0.029) were significantly linked to restenosis. However, the skewed male-to-female ratio, few surgical failures make the conclusion that sex is a risk factor speculative. Thus, only adhesion intensity can be considered a risk factor. Additionally, fibrosis assessed using trichrome staining and T-cell lymphocytic infiltration showed potential negative prognostic value in a larger cohort. Our findings indicate that patients with significant lacrimal sac adhesions, identified during endoscopic dacryocystorhinostomy, are particularly prone to postoperative restenosis. Although histological and immunohistochemical studies did not reveal a correlation between the analyzed data and restenosis, a larger patient cohort might show that fibrosis and T-cell lymphocytic infiltration could potentially have a negative prognostic value. The poorer treatment outcomes in women, seen in our study as well as in other investigations, may be due to anatomical and physiological traits of the female lacrimal drainage system that predispose them to stenosis. This hypothesis requires further study in a larger cohort.

Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis

Over half of all people diagnosed with cancer receive radiation therapy. Moderate to severe radiation dermatitis occurs in most human radiation patients, causing pain, aesthetic distress, and a negative impact on tumor control. No effective prevention or treatment for radiation dermatitis exists. The lack of well-characterized, clinically relevant animal models of human radiation dermatitis contributes to the absence of strategies to mitigate radiation dermatitis. Here, we establish and characterize a hairless SKH-1 mouse model of human radiation dermatitis by correlating temporal stages of clinical and pathological skin injury. We demonstrate that a single ionizing radiation treatment of 30 Gy using 6 MeV electrons induces severe clinical grade 3 peak toxicity at 12 days, defined by marked erythema, desquamation and partial ulceration, with resolution occurring by 25 days. Histopathology reveals that radiation-induced skin injury features temporally unique inflammatory changes. Upregulation of epidermal and dermal TGF-ß1 and COX-2 protein expression occurs at peak dermatitis, with sustained epidermal TGF-ß1 expression beyond resolution. Specific histopathological variables that remain substantially high at peak toxicity and early clinical resolution, including epidermal thickening, hyperkeratosis and dermal fibroplasia/fibrosis, serve as specific measurable parameters for in vivo interventional preclinical studies that seek to mitigate radiation-induced skin injury.

Diffusion tensor imaging of vastus lateralis in patients with inflammatory myopathies.

Inflammation in patients with myositis would increase diffusion of water molecules across sarcolemma that could be detected with the help of diffusion tensor imaging (DTI). We aimed to determine an association between DTI of vastus lateralis (VL) and histopathological findings in cases of myositis and to estimate diagnostic performance of different MRI variables in predicting histopathological outcomes. This prospective cross-sectional observational study included 43 patients with myositis. MRI of bilateral thighs with DWI/DTI protocol was performed in all the patients. Thirty-three patients further underwent biopsy of right VL muscle. Imaging analysis included grading of "Muscle oedema" based on signal intensity (SI) and extent and "fatty infiltration" based on extent on conventional sequences and, acquiring DWI and DTI parameters. Gold standard method to determine inflammation in muscles was histopathological examination. Comparison of DTI/DWI variables with clinical and histopathological variables was done. The average DWI apparent diffusion coefficient (ADC) and DTI ADC values in the patients were 1.77 ± 0.35 and 2.06 ± 0.35 respectively. The average functional anisotropy (FA) was 0.39 ± 0.17 and, the 3 eigenvalues in the patients were 2.96 ± 0.63, 2.05 ± 0.32, and 1.20 ± 0.39 respectively. VL oedema SI weighted score was the best parameter for predicting effaced fascicular architecture and marked lymphocytic inflammation in endomysium on histopathology. VL fatty infiltration weighted score was the best parameter in predicting perifascicular atrophy. Addition of DWI or DTI didn't add significantly in determining active inflammation in cases of myositis.

Can intra-articular daidzein injection reduce oxidative damage and early osteoarthritis in a rabbit temporomandibular joint model?

BackgroundOxidative damage and inflammatory cytokines in osteoarthritis (OA) exacerbate the disease course. Daidzein (DZ) has antioxidant and anti-inflammatory effects. This study evaluated the early histopathological effects of intra-articular daidzein injection on experimentally induced osteoarthritis in rabbit TMJs.MethodsThe predictor variable was intra-articular injection of DZ or a saline control. 50 µl of 3 mg/mL MIA solution was injected into the right TMJ of 16 New Zealand rabbits to induce experimental OA. One rabbit was sacrificed after 4 weeks to confirm the formation of the OA model and the OA model was obtained. The remaining 15 rabbits were randomly divided into 2 groups: an experimental group (9 rabbits) and a control group (6 rabbits). On days 1, 7, 14, and 21; 50 µl of saline solution was applied to the right TMJ of the control group and 50 µl daidzein solution (1.8 mg/ml) was applied to the right TMJ to the experimental group. After one week from the date of the last injection, the rabbits were sacrificed, and histopathological and biochemical evaluations were performed. The Shapiro-Wilk test was used to evaluate whether the variables in the study conformed to normal distribution. Mean ± SD (standard deviation) or median (interquartile range (IQR)) was used to show the descriptive statistics of the variables. T-test and Mann Whitney U test were used to compare the control and experimental groups for biochemical changes. The chi-square test was used to show the distribution of histopathological changes variables obtained within the scope of the study based on control and experimental groups. A P-value < 0.05 was considered significant for all evaluations.ResultsThere were 8 and 6 animate treated with DZ and saline, respectively. There was no statistically significant difference between groups in articular cartilage (p = 0.3), osteochondral junction (p = 0.3), subchondral bone structure (p = 1.0) or chondrocyte appearance (p = 0.4). The experimental group showed significantly lower mean values for Total Oxidant Status (TOS) (p = 0.002) and Oxidative Stress Index (OSI) (p = 0.007).ConclusionsAn intra-articular DZ injection appears to show limited reduction of oxidative damage and early OA in the rabbit TMJ. DZ might represent a promising natural compound with beneficial effects in the management of TMJ-OA.

Correlation between gastrointestinal morphological changes, enteric microbiota, and changes in live weight in dairy calves

This study aimed to quantify the association between fecal microbiota biomarkers, gastrointestinal tract (GIT) morphology, and average daily gain (ADG) of dairy calves from birth until weaned in response to feeding a direct-fed microbial (DFM) supplement as part of their milk diet. Forty-four newborn Holstein-Friesian calves were randomly assigned to Treatment (TRT) and Control (CON) groups. The TRT group calves received a once-daily dose of Lacticaseibacillus and Lentilactobacilli-based direct-fed microbial (DFM) liquid formulation. Four genera: Prevotella7, Succiniclasticum, Terrisporobacter, and Carnobacterium were enriched and identified as biomarkers of low ADG. Fourteen bacterial taxa were associated with measured gastrointestinal histopathology variables in TRT and CON groups. Although this study lists several bacterial taxa that have known roles in fermentation and nutrient metabolism vital for rumen function, their specific contributions to gastrointestinal development and weight gain remain to be fully understood. Our findings support a strategic approach to probiotic use in heifers to boost health and productivity.

Combination of single-source dual-energy computed tomography (CT) parameters and extracellular volume fraction for predicting lymphovascular and perineural invasion in colorectal cancer.

Lymphovascular invasion (LVI) and perineural invasion (PNI) are important histopathological variables that are directly related to the survival and recurrence of patients with colorectal cancer (CRC). Preoperative prediction of LVI and PNI status in CRC is helpful in selecting patients requiring appropriate adjuvant therapy and evaluating prognosis. This study aimed to investigate the value of combining single-source dual-energy computed tomography (ssDECT)-derived parameters with extracellular volume (ECV) fraction for preoperative evaluation of LVI and PNI in CRC. This retrospective study included patients with CRC who underwent contrast-enhanced ssDECT. All diagnoses were confirmed through histopathology, and the patients were classified into positive and negative groups based on the presence of LVI/PNI. Clinical data were collected. In the arterial (AP), venous (VP) and delayed phases (DP), the ssDECT-derived parameters were measured by two radiologists. The measurement consistency was evaluated using intraclass correlation coefficients. Differences between the two groups were analyzed using the t-test, Mann-Whitney U test, or Chi-square test. Binary logistic regression was employed to construct models incorporating multiple parameters. The diagnostic performance of various parameters or models was assessed by analyzing receiver operating characteristic curves. In total, 118 patients with CRC were included in the study. Serum carcinoembryonic antigen levels, T and N stages, and histological grades differed between the two groups (all P<0.05). The ssDECT-derived parameters in the VP and DP of LVI/PNI-positive group were higher than those of -negative group (all P<0.05). The ECV fraction in the DP of LVI/PNI-positive group was higher than that of -negative group (P=0.001). Discriminating capability analysis demonstrated that the diagnostic efficacies of the DP parameters were superior to those of the VP parameters, and the normalized iodine concentration in the DP exhibited the best performance [area under the curve (AUC): 0.750; 95% confidence interval (CI): 0.648-0.852]. The combination of ECV DP with clinical and ssDECT-derived parameters demonstrated the highest discriminative capability (AUC: 0.857; 95% CI: 0.786-0.928). ssDECT-derived parameters and ECV fraction may serve as non-invasive tools for predicting the LVI/PNI status in CRC.

Pseudocysts of the Adrenal Gland: A Systematic Review of Existing Scientific Literature From 2000 to 2023.

Adrenal masses are abnormal growths in the adrenal gland, comprising entities such as pheochromocytomas, adrenal adenomas, adrenocortical carcinomas, and adrenal cysts. Pseudocysts are predominant among adrenal cysts. Due to its infrequent presentation, there are no specific guidelines present in the current literature to steer its management. In such circumstances, a systematic review of the existing literature is imperative to develop comprehensive insights and evidence-based protocols. We aimed to comprehensively analyze the clinico-radiological characteristics and management outcomesof adrenal gland pseudocysts. Human adrenal gland pseudocysts identified through imaging and histopathology, as retrieved from the PubMed search engine, were included in the study. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Joanna Briggs Institute (JBI) CriticalAppraisal Checklist were used to stratify searched studies published between 2000 and 2023. A total of 39 studies were finally included, of which 36 were case reports and three case series, containing 45 patients in total. Data for clinical, radiological, histopathological, and outcome variables were collected, and descriptive analysis was carried out. All cases presented were adults with a clear female predominance of 66.67%. About 26.67% presented with no palpable mass or clinical symptoms, while 28.89% presented with vague abdominal pain. The most prevalent computed tomography (CT) finding was a cystic lesion with calcification and/or hemorrhage and/or necrosis, occurring in 17.78% of cases. Following this, a cystic lesion with only calcification was observed in 13.33% of cases, and a well-defined cystic mass/lesion was found in 11.11% of cases. The most important indication for surgery was compression effect in 44.44%, increasing size in 20.00%, and suspicion of malignancyin another 20.00% of cases. About 64.44% underwent open surgery, while 35.55% underwent minimally invasive surgery. Most patients, 95.55% of the total, had an uneventful postoperative course without any complications. Adrenal gland pseudocyst, though rare and incidental, warrants consideration in differential diagnosis as it presents with vague symptomsand sometimes no symptoms at all. Our review of existing literature highlights the importance of surgical intervention for symptomatic or potentially malignant cysts, with en bloc adrenalectomy being the preferred approach.

Single acute and repeated subacute toxicity evaluations of Annona atemoya leaf extract with in vitro anti-inflammatory potential

The nutraceutical and biological potential of Annona atemoya, a fruiting plant, has been reported. We and others have demonstrated that A. atemoya leaf extract (AAL) has various pharmacological properties, such as antioxidant, antimicrobial, and neuroprotective effects. However, knowledge about the safety and potential toxicity of AAL remains limited. We aimed to assess the potential toxicity of AAL using acute and repeated subacute oral toxicity tests in rats. In both acute and repeated subacute toxicity test, no AAL-related behavioral abnormalities or changes in mortality, food intake, body weight were observed up to a dosage of 2000 mg/kg, indicating that the median lethal dose of AAL is higher than 2000 mg/kg. In subacute toxicity tests, no significant changes in hematological and biochemical parameters, urinalysis results, and histopathological variables were observed. Therefore, the no-observed-adverse-effect level (NOAEL) of orally administered AAL was estimated to be 2000 mg/kg/day in male and female rats. We also examined the effect of AAL on the inflammatory reaction in lipopolysaccharide (LPS)-stimulated BV-2 cells. AAL treatment significantly inhibited the LPS-stimulated increases in the levels of nitric oxide (NO) and inflammatory cytokines, implying that AAL has an anti-inflammatory effect. Quality control analysis revealed that two marker compounds, rutin and isoquercitrin, were present at 27.570 and 4.322 mg/g, respectively, in a freeze-dried AAL sample and were completely eluted within 27 min. The extraction recovery was 99.47–103.80%, and the precision was ≤2.79%. Overall, these findings suggest the safety, anti-inflammatory activity, and standardization of AAL.

Breast Cancer in Male Patients of the Aconcagua Valley During the Period 2013-2018

To evaluate the clinical, epidemiological, and histopathological characteristics of breast cancer in men in the Aconcagua Valley and its relationship with patient survival. A descriptive study was conducted at the University of Valparaíso, analyzing data from seven male patients diagnosed with breast cancer at San Camilo Hospital in San Felipe between 2013 and 2018. Epidemiological, clinical, and histopathological data were analyzed using statistical software. The average age of surviving men was higher compared to those who died. However, no statistically significant association was found between clinical and histopathological variables and patient survival. Despite the limited sample size, the results suggest that factors such as age and clinical and histopathological variables are not significantly associated with survival in men with breast cancer. These findings highlight the need for further research with larger sample sizes to better understand this population's survival factors.

Learning curve and safety of the implementation of laparoscopic complete mesocolic excision with intracorporeal anastomosis for right-sided colon cancer: results from a propensity score-matched study.

Retrospective studies and randomized controlled trials support the safety of laparoscopic complete mesocolic excision (CME) for the treatment of right-sided colon cancer (RSCC). Few studies, however, examine the learning curve of this operation and its impact on safety during an implementation period. We aim to evaluate the learning curve and safety of the implementation of laparoscopic CME with intracorporeal anastomosis for RSCC. Consecutive patients undergoing a laparoscopic right colectomy with intracorporeal anastomosis for RSCC between January 2016 and June 2023 were included. Clinical, perioperative, and histopathological variables were collected. Correlation and cumulative sum (CUSUM) analyses between the operating time and case number were performed. Breakpoints of the learning curve were estimated using the broken-line model. CME and conventional laparoscopic right colectomy outcomes were compared after propensity score matching (PSM). Two hundred and ninety patients underwent laparoscopic right colectomy during study period. One hundred and eight met inclusion criteria. After PSM, 56 non-CME and 28 CME patients were compared. CME group had a non-statistically significant tendency to a longer operating time (201 versus 195min; p = 0.657) and a shorter hospital stay (3 versus 4days; p = 0.279). No significant differences were found in total complication rates or their profile. Correlation analysis identified a significant trend toward operating time reduction with increasing case numbers (Pearson correlation coefficient = - 0.624; p = 0.001). According to the CUSUM analysis, an institutional learning curve was deemed completed after 13 cases and the broken-line model identified three phases: learning (1-6 cases), consolidation (7-13 cases), and mastery (after 13 cases). The learning curve of laparoscopic CME for RSCC can be achieved after 13 cases in centers with experience in advanced laparoscopic surgery and surgeons with familiarity with this technique. Its implementation within this setting seems to be as safe as performing a conventional right colectomy.

Cryopreserved nanostructured fibrin-agarose hydrogels are efficient and safe hemostatic agents

Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.

Frequency of BRAF Mutations in Dysplastic Nevi, Lentigo Maligna, and Melanoma In Situ.

Background: In melanomas, mutations in the BRAF gene are common and their occurrence represents an early oncogenic event. Our goal was to determine and compare the frequency of BRAF gene mutations in dysplastic nevi (ND) and melanomas in situ (MIS), as well as whether there is a correlation between the presence of BRAF gene mutations and various anamnestic, clinical, and histopathologic variables. Methods: A total of 175 patients-106 with ND, 41 with MIS, and 28 with lentigo maligna (LM) were included in the study. DNA was extracted from tissue samples and analyzed using the competitive allele-specific TaqMan chain reaction by polymerase in real time to detect the presence of BRAF V600E and V600K mutations. The data were compared with anamnestic, clinical, and histopathological data. Results: There is a statistically significant correlation between the presence of BRAF mutation and the diagnosis of melanoma in situ (χ2 test, χ2 = 29.17, p < 0.0001). Patients with LM had a significantly lower incidence of BRAF mutations compared to patients with ND and MIS. There was a significant correlation between the presence of a BRAF mutation and tumor localization, as well as the age of the patient, but no statistically significant correlation between the presence of a BRAF mutation and sex, tumor size, or previous melanoma diagnosis. Conclusions: BRAF mutations in ND are essentially required; however, they are an insufficient oncogenic trigger for the development of melanoma. This research contributes to a better understanding of the etiopathogenesis of melanoma and the role of ND as possible precursor lesions.

Using Nomograms Wisely: Predicting Sentinel Node Positivity in Melanoma.

Four externally validated sentinel node biopsy (SNB) prediction nomograms exist for malignant melanoma that each incorporate different clinical and histopathologic variables, which can result in substantially different risk estimations for the same patient. We demonstrate this variability by using hypothetical melanoma cases. We compared the MSKCC and MIA calculators. Using a random number generator, 300 hypothetical thin melanoma "patients" were created with varying age, tumor thickness, Clark level, location on the body, ulceration, melanoma subtype, mitosis, and lymphovascular invasion (LVI). The chi-square test was used to detect statistically significant differences in risk estimations between nomograms. Multivariate linear regression was used to determine the most relevant contributing pathologic features in cases where the predictions diverged by > 10%. Of 300 randomly generated cases, 164 were deleted as their clinical scenarios were unlikely. The MSKCC nomogram generally calculated a lower risk than the MIA (p < 0.001). The highest risk score attained for any "patient" using MSKCC calculator was 15% achieved in one of 136 patients (0.7%), whereas using the MIA nomogram, 58 of 136 patients (43%, p < 0.001) had predicted risk >15%. Regression analysis on patients with >10% difference between nomograms revealed LVI (26, p < 0.001), mitosis (14, p < 0.001), and melanoma subtype (8, p < 0.001) were the factors with high coefficients within MIA that were not present in MSKCC. Nomograms are useful tools when predicting SNB risk but provide risk outputs that are quite sensitive to included predictors.