Histological Differentiation Research Articles

PREVALANCE OF UROTHELIAL CARCINOMA, ITS HISTOLOGICAL GRADE AND TYPE IN URINARY BLADDER OVER A PERIOD OF 2 YEARS: A STUDY IN A TERTIARY HOSPITAL IN CENTRAL INDIA

BACKGROUND:-Urinary bladder carcinoma is well known to show many histological divergent differentiation. The histological variants have important diagnostic, prognostic and therapeutic implications. The aim of the study was to find the prevalence of urothelial carcinoma in a tertiary care centre and to find the proportion of different histological grades and types of urothelial carcinoma. MATERIAL AND METHODS:- A retrospective monocentric study was done between April 2020 and April 2022 which includes 37 bladder biopsies which were received in the histopathology section of the Department of Pathology, Gajra raja medical college. Patients who refuse to give consent and those having cystitis were excluded from the study. RESULTS AND OBSERVATIONS :- Out of total 37 cases which were reviewed, the mean age was 62 years, with a male predominance (M:F ratio-3.16). Out of 37 cases, there were 8 cases each of highgrade urothelial carcinoma(21.6 %), high grade urothelial carcinoma with invasion ( 21.6 %) and high grade papillary urothelial carcinoma with invasion ( 21.6 %). There were 4 cases of high grade urothelial carcinoma with invasion with squamous differentiation ( 10.8 %), one case each of recurrent high grade urothelial carcinoma with invasion ( 2.7 %), well differentiated invasive glandular adenocarcinoma NOS (2.7%) and invasive micropapillary urothelial carcinoma with squamous differentiation ( 2.7 % ), two cases each of low grade urothelial carcinoma - 2 cases ( 5.4 %), low grade papillary urothelial carcinoma ( 5.4%) and papillary urothelial neoplasm of low malignant potential ( PUNLMP) ( 5.4 %). CONCLUSION Urinary bladder carcinoma is more common in male than females. Average age of presentation is 62 years in present study. High grade urothelial carcinoma ( 83.8 %) is more common compared to low grade ( 10.8% ). H&E staining with ancillary techniques like immunohistochemistry or molecular it can be very effective in to analyse histological variants to better understand this invasive disease hence aiding in further management of patients.

The Impact of Poorly Differentiated Histology on Immunotherapy in Advanced Gastrointestinal Cancers

Introduction: Checkpoint inhibitors (CPI) have significantly improved survival among patients with various cancer types. Prior studies have shown a correlation between immune cell infiltration and poorly differentiated cancers. This study evaluated the impact of poorly differentiated histology on survival in patients with advanced gastrointestinal cancers treated with immunotherapy. Methods: This study was a retrospective, single-center analysis of patients with gastrointestinal cancers treated with CPIs between 2016 and 2021. Univariate and multivariable analyses were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor and patient characteristics, progression-free survival, and overall survival. Results: A total of 123 patients were eligible and included in the analysis. Median age was 66 years (23–88 years). Majority had stage IV disease (89%), were white (65.5%), and were male (64.5%). Most common diagnoses were hepatocellular carcinoma (30.5%), gastric adenocarcinoma (16.5%), esophageal adenocarcinoma (17%), and colorectal cancer (19.8%). About 32% of the tumors were microsatellite instability-high (MSI-High/dMMR), with BRAF V600E mutation rate of 10%. About 25% of the patients received CPIs as initial treatment, while 35.5% had received two or more prior lines of therapy. Compared with well and moderately differentiated histology, patients with poorly differentiated tumors had a shorter median overall survival (mOS) (not reached [NR] vs. NR vs. 9.3 months, p = 0.0264). There was no statistically significant difference in median progression-free survival (mPFS) between histology types (2.5 vs. 4.2 vs. 2 months, p = 0.1314). On univariate survival analysis, moderately differentiated tumors correlated with a significantly longer mOS (HR: 0.48, CI: 0.24–0.93, p = 0.030) and mPFS (HR: 0.62, 95% CI: 0.38–1.00, p = 0.048) compared to poorly differentiated histology. Female patients (HR: 0.55, 95% CI: 0.34–0.90, p = 0.018) and the Eastern Cooperative Oncology Group (ECOG) of 1 (vs. ≥2) had significantly longer mPFS (HR: 0.58, 95% CI: 0.35–0.97, p = 0.036). ECOG of 1 also correlated with longer mOS (HR: 0.47, 95% CI: 0.23–0.94, p = 0.034). Microsatellite stable (MSS) tumors had significantly shorter mPFS (HR: 5.74, 95% CI: 2.41–13.63, p < 0.001) and mOS (HR: 5.45, 95% CI: 1.64–18.12, p = 0.006). The number of prior systemic therapies was also associated with shorter mPFS (HR: 1.19, 95% CI: 1.03–1.39, p = 0.022) and mOS (HR: 1.23, 95% CI: 1.01–1.50, p = 0.045). On multivariable analyses, ECOG status of 0/1 versus ≥2 and MSI-High/dMMR versus MSS remained significantly associated with longer mPFS and mOS. There was no correlation with histologic differentiation status, race, or mutations such as BRAF V600E or KRAS. Conclusion: Results from this study demonstrate that poorly differentiated histology was associated with shorter mOS but was not associated with improved PFS in patients treated with CPI. Treatment-naïve patients, moderately differentiated tumors, female gender, ECOG 1, and MSI-High/dMMR were most likely to benefit from CPI.

Predicting histologic differentiation of solitary hepatocellular carcinoma up to 5 cm on gadoxetate disodium-enhanced MRI

BackgroundTo establish a preoperative score based on gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) and clinical indicators for predicting histologic differentiation of solitary HCC up to 5 cm.MethodsFrom July 2015 to January 2022, consecutive patients with surgically proven solitary HCC measuring ≤ 5 cm at preoperative EOB-MRI were retrospectively enrolled. All MR images were independently evaluated by two radiologists who were blinded to all clinical and pathologic information. Univariate and multivariate logistic regression analyses were performed to identify significant clinicoradiological features associated with poorly differentiated (PD) HCC, which were then incorporated into the predictive score. The predictive score was validated in an independent validation set by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy.ResultsA total of 182 patients were included, 42 (23%) with PD HCC. According to the multivariate analysis, marked hepatobiliary phase hypointensity (odds ratio [OR], 9.98), LR-M category (OR, 5.60), and serum alpha-fetoprotein (AFP) level > 400 ng/mL (OR, 3.58) were incorporated into the predictive model; the predictive score achieved an AUC of 0.802 and 0.830 on the training and validation sets, respectively. The sensitivity, specificity, and accuracy of the predictive score were 66.7%, 85.7%, and 81.3%, respectively, on the training set and 66.7%, 81.0%, and 77.8%, respectively, on the validation set.ConclusionThe proposed score integrating two EOB-MRI features and AFP level can accurately predict PD HCC in the preoperative setting.

The use of autologous skeletal muscle-derived cells as a sling in the treatment of stress-induced urinary incontinence: An experimental study in dogs

PurposeThis is an experimental preclinical study testing the applicability of autologous skeletal muscle-derived cells as a treatment of SUI in a canine model.MethodsTen mongrel dogs were included in this study. Skeletal muscle was harvested for biopsy in 4 dogs. One month later, incontinence was induced in 8 dogs through urethrolysis. Biopsied muscle cells were incubated and expanded for 8 weeks. Muscle-derived cells were collected and covered with a polyglycolic acid (PGA) scaffold immersed in culture medium and coated with Matrigel to be used as a sling, which was placed suburethrally in 8 dogs; 4 had cell seeding, and 4 had scaffolds only. Urethral pressure (UP) measurements were performed at baseline and 2 &amp;amp; 6 weeks after sling insertion. The urethra was harvested 4 weeks after sling insertion for histopathology.ResultsOne month, a statistically significant increase of mean urethral pressure values compared to baseline was observed in all dogs with a scaffold inserted. The increase ranged from 5 to 40 cmH2O. Histopathology showed significant periurethral proliferation of skeletal muscles in 4 dogs with cell-seeded scaffolds. These levels were the maximum levels in dogs # 1 &amp;amp; 2. This was not the case in the 4 dogs that had slings only.ConclusionBased on the outcome of this preliminary experience, the use of skeletal muscle-seeded PGA scaffolds seems to be an easy and reproducible procedure which preserves histological differentiation and integrity in a canine model

An anoikis-based signature for predicting prognosis in hepatocellular carcinoma with machine learning.

Background: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality worldwide. Despite advancements in diagnosis and treatment in recent years, there is still an urgent unmet need to explore the underlying mechanisms and novel prognostic markers. Anoikis has received considerable attention because of its involvement in the progression of human malignancies. However, the potential mechanism of anoikis-related genes (ANRGs) involvement in HCC progression remains unclear. Methods: We use comprehensive bioinformatics analyses to determine the expression profile of ANRGs and their prognostic implications in HCC. Next, a risk score model was established by least absolute shrinkage and selection operator (Lasso) Cox regression analysis. Then, the prognostic value of the risk score in HCC and its correlation with clinical characteristics of HCC patients were further explored. Additionally, machine learning was utilized to identify the outstanding ANRGs to the risk score. Finally, the protein expression of DAP3 was examined on a tissue microarray (TMA), and the potential mechanisms of DAP3 in HCC was explored. Results: ANRGs were dysregulated in HCC, with a low frequency of somatic mutations and associated with prognosis of HCC patients. Then, nine ANRGs were selected to construct a risk score signature based on the LASSO model. The signature presented a strong ability of risk stratification and prediction for overall survival in HCC patients.Additionally, high risk scores were closely correlated with unfavorable clinical features such as advanced pathological stage, poor histological differentiation and vascular invasion. Moreover, The XGBoost algorithm verified that DAP3 was an important risk score contributor. Further immunohistochemistry determined the elevated expression of DAP3 in HCC tissues compared with nontumor tissues. Finally, functional analyses showed that DAP3 may promote HCC progression through multiple cancer-related pathways and suppress immune infiltration. Conclusion: In conclusion, the anoikis-based signature can be utilized as a novel prognostic biomarker for HCC, and DAP3 may play an important role in the development and progression of HCC.

Metastatic Carcinoma to the Brain with Mucinous Features in a Patient in Remission with History of Breast Lobular Carcinoma Triple Positive: A Case Report

Introduction: Breast cancer remains to be the most frequently diagnosed cancer in woman accounting for more than 2 million cases per year where it can metastasize to several organs in the body with brain metastasis being one of the most dreaded sequelae of it. Whole-brain radiosurgery, with or without surgical resection, or stereotactic radiosurgery remains to be the predominant treatment modality whereby surgical resection is limited to cases having a sole lesion identified or when located in excisable cortical regions. Case description: We presented the case of a 71-year old female patient with history of Lobular carcinoma in situ triple positive with brain metastatic carcinoma with mucinous features consistent with breast origin while being in remission after she underwent bilateral mastectomies 6 years prior to presentation with negative PET scan for any lesion other than that in the brain. Conclusion: Finding of brain metastasis with pathological features discordant with primary pathology of breast cancer, in a patient who is in remission years after undergoing bilateral mastectomies raises the question of the histological differentiation between the metastatic lesion and the primary source at the cellular level, and reflects on the relationship with receptor expression be it PR, ER or HER2.

Sinonasal adenocarcinomas: Retrospective analysis from an oncology center

Introduction and objectivesSinonasal adenocarcinomas are rare and heterogeneous tumors and for this reason remain understudied. Our purpose is to analyze clinical presentation, outcomes and factors affecting survival of patients with sinonasal adenocarcinomas, treated at our institution. Material and methodsRetrospective review of clinical records of patients with sinonasal adenocarcinoma, treated at a tertiary oncology institution (January 2010 to December 2019). ResultsSixty patients diagnosed with adenocarcinoma were included, with male preponderance (54.90%) and a mean age of 57.5±14.9 years. Adenocarcinoma was the most frequent type of sinonasal cancer, contrary to previous reports from our institution. In most patients, it was detected at an advanced disease stage, significantly decreasing their survival rate when compared to patients diagnosed at initial stages (p<0.029). Intestinal type adenocarcinoma was established in 47 patients, the most frequent being the colonic subtype (24%). Tumors with good/moderate histologic differentiation presented a survival advantage over those that were poorly differentiated (p=0.043). The most common treatment modality was surgery followed by radiotherapy. Endoscopic resection was performed in 53% of the patients and an external approach was used in 40% of the patients. Estimated overall survival rates at 3 and 5-years were 64% and 53%, respectively, and cancer specific survival 72% and 65%, for the same period. Recurrence rate was 32% and occurred mainly locally. Disease Free Survival rate was 71% at 3 years and 65% at 5 years. ConclusionsDespite being the most common sinonasal malignancy in our sample, in contrast to other series, sinonasal adenocarcinomas are still rare tumors with a substantial local failure rate of around 30%. Advanced stage at diagnosis and histologic differentiation grade negatively affected prognosis of these tumors.

ZFPM2-AS1: An Oncogenic Long Non-coding RNA in Multiple Cancer Types.

Long non-coding RNA (lncRNA) is a novel kind of RNA transcript with lengths greater than 200 nucleotides. Functionally, lncRNAs lack the potential to encode peptides or proteins. Previous studies unveiled that lncRNA participated in numerous physiological and pathological processes, including cancer, aging, and immune responses. Newly discovered long noncoding RNA zinc finger protein, Friend of GATA (FOG) family member 2-antisense 1 (ZFPM2-AS1), located on the 8q23 chromosome, acts as a tumor stimulator in various cancer types, including Breast Cancer (BC), Colorectal Cancer (CRC), Esophageal Squamous Cell Carcinoma (ESCC), Gastric Cancer (GC), glioma, hepatocellular carcinoma (HCC), Lung Adenocarcinoma (LUAD), melanoma, non-small cell lung cancer (NSCLC), Retinoblastoma (RB), Small Cell Lung Cancer (SCLC) and thyroid cancer. Accumulative evidence also elucidated that ZFPM2-AS1 dysregulation was related to tumor proliferative, migratory, invasive, anti-apoptotic, and pro-epithelial-tomesenchymal Transition (EMT) effects, larger tumor volume, higher tumor weight, advanced tumor stage, high rates of lymphatic metastasis, distant metastasis, poor prognosis, histological differentiation, higher TNM (tumor, node, metastases) stage, depth of tumor invasion, reduced overall and disease- free survival, vein invasion, and shorter 5-year overall survival. Mechanistically, ZFPM2-AS1 acted as a ceRNA to play its oncogenic role. Thus, this study summarized the specific mechanisms of the lncRNA ZFPM2-AS1 in the aforementioned cancer types to reveal its novel application in cancer diagnosis, treatment, and prognosis.

Microglandular adenosis of the breast

The presented case describes the difficulties of diagnosis of the breast microglandular adenosis (MGA), taken by clinicians for a malignant process due to the nature of growth and large size. Criteria for histological and immunohistochemical diagnosis and differentiation of MGA with malignant neoplasms, in particular, with tubular breast carcinoma, are presented. Taking into account the rarity of the pathology and the absence of described cases in the Russian-language literature, the observation is of interest to pathologists and clinicians.

Clinicopathological Parameters and Immunohistochemical Expression of EGFR in Colorectal Carcinoma: A Cross-sectional Study

Introduction: Colorectal Carcinoma (CRC) is the third most common type of cancer worldwide and is one of the leading causes of cancer-related death. Adenocarcinoma is the most common type. Histopathological examination is necessary to determine the type and extent of the tumour, which is essential for patient management and prognosis. Molecular markers play a major role in CRC, among which Epidermal Growth Factor Receptor (EGFR) has prognostic significance. Aim: The aim of this study was to evaluate the immunohistochemical expression of EGFR in cases of colonic carcinoma and analyse its relationship with various histological and clinical parameters. Materials and Methods: An observational (cross-sectional) study was conducted in the Department of Pathology, Sree Mookambika Institute of Medical Sciences, Kulasekharam, Kanyakumari district, Tamil Nadu, India. Data from colonic carcinoma patients confirmed by Haematoxylin and Eosin (H&amp;E) staining were collected over a three-year period from January 2019 to December 2021. A total of 58 cases were included. The characteristics studied included age, sex, Carcinoembryonic Antigen (CEA) levels, tumour site, size, degree of histological differentiation (well, moderate, poor), TNM staging, and lymph node status. The EGFR score was obtained by multiplying the grade (% positive cells) by the intensity, and a composite score ranging from 0 to 9 was obtained. This score was used to define low EGFR expression (&lt;6) or high EGFR expression (&gt;6). Analysis was performed using the Chi-square test in Statistical Package for the Social Sciences (SPSS) version 20.0. Results: Among the 58 patients included in the study, the most common age group affected by CRC was 61 to 70 years (28 cases; 48.3%), with a mean age of 63.32±14.36 years. The most common histological variant was low-grade adenocarcinoma (47 cases; 81.03%). EGFR reactivity was positive in 50 patients (86.20%). EGFR overexpression was significantly associated with histopathological type (low-grade adenocarcinoma) and tumour stage, with p-values of 0.03 and 0.001, respectively. Conclusion: Immunohistochemical overexpression of EGFR in CRC is associated with histopathological type and tumour staging in this study. This overexpression is associated with poor prognosis and can be used as a predictive marker for patients who yield positive results with chemotherapy.

Right colon cancer: The influence of specific location on recurrence and survival

AimThis study aimed to investigate whether the site of the tumour within the right colon affects survival in patients who underwent right colectomy for colon cancer. MethodsAn observational retrospective longitudinal study was performed in patients who underwent right colectomy for non-metastatic, invasive right-sided colon cancer. Patients were categorized into two groups based on tumour location: (i) caecum and ascending colon; (ii) hepatic flexure and proximal transverse colon. Demographic and clinical features were characterized, and a survival analysis was performed. ResultsOf the 198 patients enroled in the study, 134 (67.8%) had caecal or ascending colon cancer and 64 (32.3%) had hepatic flexure or transverse colon cancer. Seventy (35.4%) were female and the mean age at the time of surgery was 71.6 (SD 11.4). The groups were comparable with respect to the number of lymph nodes sampled, the pTNM stage, the histological differentiation grade and the likelihood of patients receiving adjuvant chemotherapy. Recurrence rate was nearly twice as high in the hepatic flexure and proximal transverse colon group (12.5% vs 6.7%), but this difference was not statistically significant (p = 0.174). Kaplan-Meier analysis showed no differences in disease-free (p = 0.255) and overall survival (p = 0.258) between the groups. ConclusionIn our population, specific location of right-sided colon cancers does not appear to have an influence on survival. Further investigation is needed to determine if tumour subsite has an impact on the recurrence rate, and whether it should be considered in defining prognosis and treatment.

Адренергическая и холинергическая иннервация опухолеподобных образований голосовых складок у больных c вегетативными расстройствами

To develop therapeutic measures aimed at improving the voice and including exposure to specific mechanisms of the autonomic nervous system (ANS), it is necessary to know the features of the autonomic innervation of the vocal folds, which has a significant impact on the work of the vocal apparatus by regulating the trophic state of the elements forming it. Objective. Histochemical detection of adrenergic and cholinergic nerve fibers in tumor-like formations of vocal folds in patients with autonomic disorders. Materials and methods. A comprehensive examination of 64 patients with impaired voice function was carried out. During the examination, the medical history was studied, an objective examination of the upper respiratory tract according to generally accepted methods and with the help of video stroboscopic instrumentation, a cytological examination of touch preparation from the affected laryngeal area, and a study of the functional state of the ANS from the surgical material, including histological and histochemical examination of the removed tissue, were carried out. As a result, all patients were clinically diagnosed with a vocal fold polyp. Results. Histological, histochemical, and cytological studies have shown that in 80% of patients morphofunctional alterations of the vocal folds were combined with inadequate autonomic maintenance of activity. The data obtained allow us to assume that hyperplastic compensatory and adaptive responses of the laryngeal mucosa pass to pathological dystrophic changes and may contribute to deviations of the mucosal epithelium from normal histological differentiation toward atypia. Such changes create conditions for the development of benign and malignant tumors. Conclusion. In general, the data obtained give reason to believe that with prolonged dysfunction of the ANS a neurodystrophic process develops in the body, taking part in the pathogenesis of various diseases, including diseases of the larynx. With this in mind when performing preventive and therapeutic measures aimed at patients with tumor-like formations of the vocal folds, it is necessary to assess the functional state of the ANS and include measures to correct autonomic parameters in the general treatment and rehabilitation regimen.

Management of Appendix Neuroendocrine Neoplasms: Insights on the Current Guidelines.

Appendiceal neuroendocrine neoplasms (ANENs) usually present as incidental findings at the time of appendectomy for acute appendicitis. They are rare, accounting for only 0.5-1% of intestinal neoplasms; they are found in 0.3-0.9% of all appendectomy specimens. They are usually sporadic tumors. There are several histological types including well-differentiated neuroendocrine tumors (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). Histologic differentiation and the grade of well-differentiated NETs correlate with clinical behavior and prognosis. Management varies based on differentiation, aggressiveness, and metastatic potential. There is debate about the optimal surgical management for localized appendiceal NETs that are impacted by many factors including the tumor size, the extent of mesoappendiceal spread, lymphovascular invasion and perineural involvement. In addition, the data to guide therapy in metastatic disease are limited due to the paucity of these tumors. Here, we review the current advances in the management of ANENs within the context of a multidisciplinary approach to these tumors.

Oral cavity cancer in patients from the department of head and neck surgery – chair and otorhinolaryngology service of the Hospital de Clínicas – National University of Asunción

Introduction: The oral cavity is continuously exposed to inhaled and ingested carcinogens (mainly tobacco and alcohol), and therefore it is the most common site for the origin of neoplasms in the head and neck region. Methods: A descriptive, retrospective, observational study of non-probabilistic sampling of consecutive cases was carried out. Adult patients with a clinical and pathological diagnosis of oral cavity cancer were included. Results: A series of 17 cases of oral squamous cell carcinoma was included, 13 men (76%) and 4 women (24%). The age of the individuals ranged between 32 and 73 years. 65% of the patients were smokers, and 71% reported consumption of alcoholic beverages. The tongue was the most frequent tumor location, 71% were in stage IV, and with a moderate degree of histological differentiation. Conclusion: Most of the patients in this study were males between 50 and 70 years of age. A high percentage of patients reported smoking, and an even higher percentage of alcohol consumption. The most frequently affected subsite is the tongue, in advanced stages and a moderate degree of differentiation.

Morphological characteristics of the duodenal papilla magna tumors

Objective. Studying of morphological characteristics of the duodenal papilla magna malignant tumors on the own material of the Division of Pathological Anatomy and Cytology of the Shalimov National Institute of Surgery and Transplantology.&#x0D; Materials and methods. Into the investigation 82 patients were included, to whom pancreaticoduodenectomy was performed for duodenal papilla magna malignant tumors in 2019 – 2021 yrs with further conduction of morphological analysis of the specimen excised. The average age of the patients have constituted (61.1 ± 8.1) yrs old.&#x0D; Results. There were revealed 8 histological types of the tumors, most frequent of them – adenocarcinomas of pancreatobiliary and intestinal types. These two variants were compared. They did not differ for the age and gender (р&gt;0,05), but statistically significantly differed for the histological differentiation degree and tumoral spread: р =0.039 and р = 0.003, accordingly. Thus, in the pancreatobiliary type of adenocarcinoma the tumors with low differentiation level (G3) were in 1.9 times more frequent, than in adenocarcinomas of intestinal type: 22.9 and 11.8%, and in 2.8 times more frequently the more spread tumors were revealed (рТ3а–Т3b): 65.7 and 23.5%, accordingly. As well, in the patients with adenocarcinomas of pancreatobiliary type a positive status of regional lymph nodes was revealed more frequently – in 57.1%, than in patients with adenocarcinomas of intestinal type – 44.1%.&#x0D; Conclusion. Duodenal papilla magna malignant tumors – a heterogeneous group of tumors. Adenocarcinomas of pancreatobiliary and intestinal types are the most prevalent. Pancreatobiliary adenocarcinoma, as a histological type, is more aggressive, than intestinal adenocarcinoma.

Tumor Differentiation is the Dominant Prognostic Factor for Patients with Colorectal Neuroendocrine Neoplasms with Distant Metastasis.

Colorectal neuroendocrine neoplasms (NENs) are rare tumors. The prognosis and prognostic factors of metastatic colorectal NENs have not been fully elucidated. We retrospectively enrolled 77 consecutive patients diagnosed with colorectal NENs with synchronous distant metastases between 2000 and 2021. All patients were assigned to the neuroendocrine tumor (NET) group or the neuroendocrine carcinoma (NEC) group based on histological differentiation. Propensity score matching (PSM) was performed to minimize confounding bias. The Kaplan-Meier method was used to calculate the survival rates. Univariate and multivariate logistic regression analyses were performed to identify prognostic factors. In total, 35 (45.5%) and 42 (54.5%) patients had well-differentiated NETs and poorly differentiated NECs, respectively. The median overall survival (OS) was 26 months for the entire cohort, and the 1-year, 3-year, and 5-year OS rates were 69.4%, 41.4%, and 27.8%, respectively. In the subgroup analysis, the median OS was 62 and 10 months for NETs and NECs, respectively. Univariate analysis demonstrated that patients with a primary tumor located in the colon, ulcerative tumors and poorly differentiated tumors were at higher risk for poorer progression-free survival (PFS) and OS. However, only histological differentiation was identified as an independent factor affecting OS (hazard ratio (HR) = 8.28, 95% confidence interval (CI): 2.98-23.01, P < 0.001) in multivariate analysis. After PSM, histological differentiation was further confirmed as the dominant factor affecting OS (HR = 6.09, 95% CI: 1.96-18.95, P=0.002)). Histological differentiation was the most dominant prognostic factor in patients with metastatic colorectal NENs. Patients with well-differentiated NETs had a good chance of long-term survival.

Tumor budding as an indicator for lymph node metastasis and prognosis of early gastric cancer.

Tumor budding, considered as an independent risk factor reflecting prognosis of some malignant tumors, has been recognized as an important clinicopathological indicator of colorectal carcinoma. However, the evaluation of tumor budding and its clinicopathological significance in gastric cancer remain controversial. To investigate the relationship between tumor budding and clinical biological behavior of early gastric cancer (EGC) and assess the predictive value of tumor budding for lymph node metastasis as well as its impact on prognosis of EGC patients. Tissue specimens of 164 EGC patients who underwent radical gastrectomy between June 2011 and January 2017 from a single center were selected to carry out HE and CK staining respectively, so as to evaluate tumor budding under light microscopy. Clinicopathological data and follow-up results of all EGC patients were collected for statistical analysis among tumor budding, EGC clinicopathological factors and prognosis. Of all 164 EGC patients, there were 84 (51.2%) cases with mucosal invasion and 80 (48.8%) cases with submucosal invasion. Meanwhile, 32 cases (19.5%) had lymph node metastasis, 19 (11.6%) had lympho-vascular invasion and 4 (2.4%) had early recurrence. Tumor budding were observed in 90 (54.9%) patients, with low-grade budding 68 (41.5%) cases and high-grade budding 22 (13.4%) cases. Tumor budding was closely correlated with tumor size (c2 = 6.609, P = 0.037), tumor histologic differentiation (c2 = 10.522, P = 0.032), depth of invasion (c2 = 8.787, P = 0.012), lymph node metastasis (c2 = 24.226, P < 0.01), TNM stage (c2 = 24.226, P < 0.01), lympho-vascular invasion (c2 = 8.225, P = 0.016) and early recurrence (c2 = 6.462, P = 0.040). Additionally, tumor budding was correlated with postoperative survival rate as well. Multiple regression analysis revealed that tumor budding was an independent influencing factor of postoperative 3-year survival rate, 5-year survival rate, OS, DFS and DSS (P < 0.05). Furthermore, tumor budding was an independent risk factor of lymph node metastasis of EGC patients, and high-grade budding was a high-risk indicator of lymph node metastasis. Tumor budding is related to tumor size, tumor histologic differentiation, depth of invasion, lymph node metastasis, lympho-vascular invasion and early recurrence of EGC. Tumor budding, especially high-grade budding can serve as an indicator for predicting lymph node metastasis of EGC, and high-grade budding could be an important parameter for evaluating prognosis of EGC patients.

Prognostic impact of preoperative skeletal muscle change from diagnosis to surgery in patients with perihilar cholangiocarcinoma.

Loss of skeletal muscle mass is a prognostic factor after surgery for gastrointestinal cancers. The treatment for perihilar cholangiocarcinoma (PHC) is a highly invasive surgery. Biliary drainage and portal vein embolization, which can prolong the preoperative waiting time (PWT), are often required before surgery. Assuming that the skeletal muscle mass can change during PWT, we investigated the clinical effect of skeletal muscle change on surgical outcomes of PHC. We retrospectively reviewed the medical records of 89 patients who underwent curative surgery for PHC from January 2013 to December 2019. We defined the psoas muscle area (PMA) at the third lumbar vertebra as the skeletal muscle mass. The PMA just before surgery was divided by that at the time of diagnosis, and we defined it as the rate of change of PMA (CPMA). Patients were divided into two groups according to CPMA: wasting (n=44, below the median CPMA) and no-change (n=45, above the median CPMA). The median PWT was 63 d, and CPMA was 96.1%. The median recurrence-free survival and overall survival were significantly shorter in the wasting group than in the no-change group (8.0 vs 33.2 mo, P =0.001 and 14.2 vs 48.7 mo, P <0.001, respectively). Multivariate analysis revealed that histological differentiation, R1 resection, lymph node metastasis, and preoperative skeletal muscle wasting were independent prognostic factors of PHC. This study suggests that preoperative skeletal muscle wasting in patients with PHC has a negative effect on survival outcomes.

Primary fibrosarcoma of the distal femur. Report of a rare case

Fibrosarcoma of bone is a relatively rare malignant neoplasia, representing less than 5% of all bone tumors. It is distinguished from other bone sarcomas by the presence of spindle-shaped tumor cells located among intertwining bundles of collagen fibers, without any other type of histological differentiation, such as the formation of cartilage or bone.&#x0D; In the present report, we present a rare case of primary fibrosarcoma in the distal femur in a 45-year-old patient with complaints of mild pain and swelling in the right knee joint for approximately 6 months. After imaging evaluation, a biopsy was performed; in the second stage, a subsequent resection of 16 cm of the distal femur and its replacement with a tumor endoprosthesis was performed. Three months postoperatively, no local recurrence or metastasis of the tumor was observed.

Molting-related proteases in the brown planthopper, Nilaparvata lugens

Digestion and absorption of old cuticles during insect molting are necessary for new cuticle formation, during which complicated enzyme catalysis is essential. To date, a few carboxypeptidases, aminopeptidases and serine proteases (mostly trypsins) connected with cuticle digestion, zymogen activation and histological differentiation during the ecdysis of lepidopteran, dipteran and hymenopteran insects have been identified. However, little is known about these proteins in hemimetabolous insects. In this study, we identified 33 candidate trypsin and trypsin-like homologs, 14 metallocarboxypeptidase and 32 aminopeptidase genes in the brown planthopper Nilaparvata lugens, a hemipteran rice pest. Among the proteins encoded by these genes, 9 trypsin-like proteases, 3 metallocarboxypeptidases and 1 aminopeptidase were selected as potential procuticle hydrolases by bioinformatics analysis and in vivo validation. RNA interference targeting these genes demonstrated that 3 trypsin-like proteases (NlTrypsin-8, NlTrypsin-29 and NlTrypsin-32) genes and 1 metallocarboxypeptidase (NlCpB) gene were found to be essential for ecdysis in N. lugens; specifically, gene silencing led to incomplete cuticle degradation and arrested ecdysis, causing lethal morphological phenotype acquisition. Spatiotemporal expression profiling by quantitative PCR and western blotting revealed their specific expression in the integument and their periodic expression during each stadium, with a peak before ecdysis and eclosion. Transmission electron microscopy demonstrated corresponding ultrastructural defects after RNAi targeting, with NlCpB-silenced specimens having the most undigested old procuticles. Immunohistochemical staining revealed that NlTrypsin-8, NlTrypsin-29 and NlCpB were predominantly located in the exuvial space. This research further adds to our understanding of proteases and its potential role in insect ecdysis.