Is annual screening by fecal immunochemical test necessary after a recent colonoscopy?

Objective: The population-based colorectal cancer screening guidelines in Japan recommend an annual fecal immunochemical test (FIT). However, there is no consensus on the need for annual FIT screening for patients who recently performed a total colonoscopy (TCS). Therefore, we evaluated the repeated TCS results for patients with positive FIT after a recent TCS to assess the necessity of an annual FIT. Methods: We reviewed patients with positive FIT in opportunistic screening from April 2017 to March 2022. The patients were divided into two groups: those who had undergone TCS within the previous 5 years (previous TCS group) and those who had not (non-previous TCS group). We compared the detection rates of advanced neoplasia and colorectal cancer between the two groups. Results: Of 671 patients, 151 had received TCS within 5 years and 520 had not. The detection rates of advanced neoplasia in the previous TCS and non-previous TCS groups were 4.6% and 12.1%, respectively (p < 0.01), and the colorectal cancer detection rates were 0.7% and 1.5%, respectively (no significant difference). The adenoma detection rates were 33.8% in the previous TCS group and 40.0% in the non-previous TCS group (no significant difference). Conclusions: Only a few patients were diagnosed with advanced neoplasia among the patients with FIT positive after a recent TCS. For patients with adenomatous lesions on previous TCS, repeated TCS should be performed according to the surveillance program without an annual FIT. The need for an annual FIT for patients without adenomatous lesions on previous TCS should be prospectively assessed in the future.

Steroid lifting method during endoscopic submucosal dissection: A novel strategy for stricture prevention.

A 73-year-old male patient was referred to us with a long Barrett's esophagus (BE). He had a history of pulmonary embolism under anticoagulant therapy. Esophagogastroduodenoscopy showed a C8M9 BE with no macroscopic lesions. Random biopsies from the BE revealed multifocal high-grade dysplasia. The case was discussed in a multidisciplinary team conference and the decision for full resection of BE with endoscopic submucosal dissection (ESD) was made. Considering the large ESD resection and the high risk of stricture, we developed a novel preventive technique: the "steroid lifting method" for submucosal injection during ESD. Complete circumferential ESD with en bloc resection was performed using the "steroid lifting method", without adverse events. Oral liquids were initiated on day 1 and the patient was discharged on day 4. Oral prednisolone (30 mg per day) was started and tapered for a total of 6 weeks. The pathological examination confirmed multifocal high-grade dysplasia, with radical and curative resection. The patient had neither stricture, dysphagia nor recurrence of Barrett's mucosa at the 2, 6, 12, and 24-month follow-up. International guidelines recommend oral prednisolone and triamcinolone injection to prevent stricture formation in large ESD of esophageal squamous cell carcinoma. However, there is no solid data on BE ESD. The risk factors for stricture formation and the optimal preventive management after large BE ESD is not known. The "steroid lifting method" might be an option in this context. Large prospective studies addressing stricture formation and preventive measures on BE ESD are necessary.

Association between dyslipidemia and cervical intraepithelial neoplasia: A case-control study in south-western Uganda.

Background: Altered lipid levels may be associated with the development of a number of malignancies, including cancer of the cervix. However, there is limited understanding of this relationship in the rural Ugandan context. Objective: We investigated the connection between dyslipidaemias and cervical intraepithelial neoplasia (CIN) among women attending the cervical cancer clinic at Mbarara Regional Referral Hospital in south-western Uganda. Methods: This unmatched case-control study was conducted between December 2022 and February 2023 and included women with CIN (cases) and women without intraepithelial lesions (controls) in a 1:1 ratio. Participants were selected based on cytology and/or histology results, and after obtaining written informed consent. Demographic data were collected, and venous blood was drawn for lipid profile analysis. Dyslipidaemia was defined as: total cholesterol > 200 mg/dL, low-density lipoprotein > 160 mg/dL, triglycerides > 150 mg/dL, or high-density lipoprotein < 40 mg/dL. At diagnosis, cases were categorised as either CIN1 (low grade) or CIN2+ (high grade). Results: Among the 93 cases, 81 had CIN1, while 12 had CIN2+. Controls had a 13.9% (13/93) prevalence of high triglycerides and cases had a prevalence of 3.2% (3/93; p = 0.016). Reduced high-density lipoprotein was the most prevalent dyslipidaemia among cases (40.9%; 38/93). Statistically significant associations were found between high serum triglycerides and CIN (odds ratio: 1.395, 95% confidence interval: 0.084-1.851, p = 0.007). Conclusion: A notable association was observed between triglyceride dyslipidemia and CIN. Further studies into biochemical processes and interactions between lipids and cervical carcinogenesis are recommended through prospective cohort studies. What this study adds: This research provides additional information on the potential role of lipids in cervical carcinogenesis among women in rural Uganda. It also presents the possible prevalence of multimorbidity involving cervical cancer and cardiovascular diseases, particularly in low-resource settings lacking preventive measures against the increasing prevalence of dyslipidaemia.

Early detection of multiple endocrine neoplasia type 1: A case report.

BACKGROUND: Multiple endocrine neoplasias (MENs) are a group of hereditary diseases involving multiple endocrine glands, and their prevalence is low. MEN type 1 (MEN1) has diverse clinical manifestations, mainly involving the parathyroid glands, gastrointestinal tract, pancreas and pituitary gland, making it easy to miss the clinical diagnosis. CASE SUMMARY: We present the case of a patient in whom MEN1 was detected early. A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hospital. Blood tests at admission revealed hypercalcemia and hypophosphatemia, and emission computed tomography of the parathyroid glands revealed a hyperfunctioning parathyroid lesion. Gastroscopy findings suggested a duodenal bulge and ulceration. Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb. Further blood tests revealed elevated levels of serum gastrin. Surgery was performed, and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy. The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year. CONCLUSION: For patients who present with gastrointestinal symptoms accompanied by hypercalcemia and hypophosphatemia, clinicians need to be alert to the possibility of MEN1.

Diagnosis and management of a case of gestational trophoblastic neoplasia with lumbosacral metastases.

Gestational trophoblastic neoplasia (GTN) with spinal metastasis is rare with few documented cases worldwide. Few studies have explored chemotherapy combined with radiotherapy in the treatment of such cases. However, because of its rarity, there is still no standardized treatment regimen. A 34-year-old Gravida 1 Para 0 (0010) was diagnosed with GTN with metastasis to the lumbosacral spine, resulting in conus medullaris syndrome with lumbar radiculopathy. She presented with a 14-month history of amenorrhea, left lower extremity pain, and urinary and bowel retention. On examination, there was a 10.0 × 7.0 cm lumbosacral mass and atrophy of the left lower extremity. Transvaginal ultrasound showed a cul de sac mass, and diluted ß-human chorionic gonadotropin (ß-hCG) titer was markedly elevated at more than 1000 000 mIU/mL. Magnetic resonance imaging (MRI) of the lumbosacral spine showed an ill-defined sacral mass measuring 13.3 × 11.5 × 6.3 cm with spinal canal, bone, muscle, and nerve root involvement. She was treated with 10 cycles of EMACO and palliative radiotherapy with 10 sessions of 30 Gy of external beam radiation therapy directed toward the lumbosacral mass. Repeat MRI showed a decrease in size of the mass to 6.6 × 8.2 × 4.1 cm with concurrent decrease in ß-hCG to 1.30 mIU/ml, and resolution of leg pain and urinary and bowel symptoms. She was declared to be in remission 3 months after the last cycle of EMACO.

MRI of a presumptive intracranial histiocytic sarcoma with extracranial extension in a cat.

Case summary: A 4-year-old female neutered Scottish Fold shorthair cat was presented for further investigation of circling towards the right. MRI of the brain revealed an extensive, right-sided temporal muscle lesion with associated frontotemporal bone osteolysis, intracranial, extra-axial extension along the calvarial convexity with severe pachy- and leptomeningeal thickening and contrast enhancement, and an intra-axial space-occupying lesion in the right piriform lobe. The regional lymph nodes were moderately enlarged. Cytology of the right parotid lymph node and the temporal muscle was performed and histiocytic sarcoma (HS) was diagnosed. The owners elected euthanasia. Relevance and novel information: HS of the central nervous system (CNS) is a very rare neoplastic condition in cats. Although a few case reports mention MRI, to our knowledge, the characterisation of MRI features of feline CNS HS have not been investigated in detail. Therefore, the aim of this case report was to describe the MRI characteristics in a feline HS involving not only the CNS, but also the fronto-temporal bone, temporal muscle and the regional lymph nodes. In particular, aggressive neoplastic bone invasion was a novel finding.

Life history traits and cancer prevalence in birds.

Background and objectives: Cancer is a disease that affects nearly all multicellular life, including the broad and diverse taxa of Aves. While little is known about the factors that contribute to cancer risk across Aves, life history trade-offs may explain some of this variability in cancer prevalence. We predict birds with high investment in reproduction may have a higher likelihood of developing cancer. In this study, we tested whether life history traits are associated with cancer prevalence in 108 species of birds. Methodology: We obtained life history data from published databases and cancer data from 5,729 necropsies from 108 species of birds across 24 taxonomic orders from 25 different zoological facilities. We performed phylogenetically controlled regression analyses between adult body mass, lifespan, incubation length, clutch size, sexually dimorphic traits, and both neoplasia and malignancy prevalence. We also compared the neoplasia and malignancy prevalence of female and male birds. Results: Providing support for a life history trade-off between somatic maintenance and reproduction, we found a positive relationship between clutch size and cancer prevalence across Aves. There was no significant association with body mass, lifespan, incubation length, sexual dimorphism, and cancer. Conclusions and implications: Life history theory presents an important framework for understanding differences in cancer defenses across various species. These results suggest a trade-off between reproduction and somatic maintenance, where Aves with small clutch sizes get less cancer.

Papillary Thyroid Carcinoma, Cushing Disease, and Adrenocortical Carcinoma in a Patient with Li-Fraumeni Syndrome.

Background/Objective: Li-Fraumeni syndrome (LFS) is an inherited sequence variant in TP53 characterized by the early onset of various core malignancies including adrenocortical carcinoma (ACC), sarcomas, breast cancer, leukemias, and central nervous system tumors. We present a case of a patient with LFS who developed endocrine neoplasms not classically seen in LFS in addition to developing ACC. Case Report: A 26-year-old nonbinary individual assigned female at birth with a history of LFS complicated by osteosarcoma of the jaw was incidentally found to have thyroid and sellar masses on surveillance magnetic resonance imaging. Fine-needle aspiration of thyroid mass confirmed papillary thyroid carcinoma, and the patient underwent total thyroidectomy. Pituitary workup was notable for laboratory test results consistent with adrenocorticotropic hormone-dependent hypercortisolism; the patient underwent resection of the pituitary lesion. The patient was subsequently noted on abdominal imaging to have a new left adrenal mass; they underwent left adrenalectomy with pathology consistent with ACC. Discussion: There is limited literature on the relationship between LFS and thyroid and pituitary neoplasms. Genetic testing has suggested that TP53 sequence variants may play a role in tumorigenesis in thyroid and pituitary neoplasms; however, most of the current literature is based on evidence of somatic rather than germline sequence variants. Conclusion: This case highlights a patient with LFS with neoplasia of multiple endocrine organs including ACC, which is a classic finding, as well as papillary thyroid carcinoma and Cushing disease. Further investigation may be necessary to assess if patients with LFS are at a higher risk of various endocrine neoplasms in addition to the core malignancies classically described because this could affect future screening protocols.

Risk of developing high-grade squamous intraepithelial lesions or anal cancer after anal condylomata treatment in people living with HIV.

AIM: To assess the risk and natural history of developing advanced anal disease after diagnosis of anal condyloma in people living with HIV (PLWH). METHODS: This was a single-centre retrospective cohort study of PLWH and anal condyloma from 2001 to 2021. Patients who developed advanced anal disease (AAD; anal high-grade squamous intraepithelial lesions and/or anal cancer) were compared to those who did not progress (non-AAD). We assessed the potential association between AAD and condyloma location, recurrence, and treatment modality. AAD-free survival was calculated utilizing Kaplan-Meier methods. RESULTS: A total of 118 PLWH and anal condyloma were included. Mean overall follow-up time was 9.3 years. A total of 31% of patients developed AAD (n = 37). Average time to AAD from condyloma diagnosis was 5.6 years. On multivariate analysis, risk for AAD development was associated with perianal location of condyloma (OR 4.39, p = 0.038) and increased time from initial condyloma diagnosis (OR 1.12, p = 0.008). Higher CD4/CD8 ratios were associated with lower risk of AAD (OR 0.15, p = 0.029). Condyloma recurrence and treatment type were not associated with development of AAD. AAD-free survival was longer in those with intra-anal only condyloma versus those with either perianal disease alone or combined intra-anal/perianal disease (mean survival times: 22.8 vs. 8.7 vs. 10.7 years, p = 0.017). CONCLUSION: Our study demonstrates the need for careful, long-term follow-up of PLWH and condyloma, particularly in the setting of perianal disease and low CD4/CD8 ratio. Risk of anal disease progression is present even in the setting of condyloma regression following treatment.

Case report: Comprehensive follow-up of a Colombian family carrying a novel MEN1 variant linked to a rare ACTH-producing pancreatic neuroendocrine carcinoma.

Background: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder marked by pathogenic variants in the MEN1 tumor suppressor gene, leading to tumors in the parathyroid glands, pancreas, and pituitary. The occurrence of ACTH-producing pancreatic neuroendocrine carcinoma is exceedingly rare in MEN1. Case presentation: This report details a Colombian family harboring a novel MEN1 variant identified through genetic screening initiated by the index case. Affected family members exhibited primary hyperparathyroidism (PHPT) symptoms from their 20s to 50s. Uniquely, the index case developed an ACTH-secreting pancreatic neuroendocrine carcinoma, a rarity in MEN1 syndromes. Proactive screening enabled the early detection of pituitary neuroendocrine tumors (PitNETs) as microadenomas in two carriers, with subsequent surgical or pharmacological intervention based on the clinical presentation. Conclusion: Our findings underscore the significance of cascade screening in facilitating the early diagnosis and individualized treatment of MEN1, contributing to better patient outcomes. Additionally, this study brings to light a novel presentation of ACTH-producing pancreatic neuroendocrine carcinoma within the MEN1 spectrum, expanding our understanding of the disease's manifestations.

Distribution and diagnostic value of single and multiple high-risk HPV infections in detection of cervical intraepithelial neoplasia: A retrospective multicenter study in China.

The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.

Acvr1b loss increases formation of pancreatic precancerous lesions from acinar and ductal cells of origin.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) can develop from precursor lesions, including pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). Previous studies indicated that loss of Acvr1b accelerates the Kras-mediated development of papillary IPMN in the mouse pancreas, however, the cell type predominantly affected by these genetic changes remains unclear. METHODS: We investigated the contribution of cellular origin by inducing IPMN associated mutations- KRASG12D expression and Acvr1b loss - specifically in acinar (Ptf1aCreER;KrasLSL-G12D;Acvr1bfl/fl mice) or ductal (Sox9CreER;KrasLSL-G12D;Acvr1bfl/fl mice) cells in mice. We then performed MRI imaging and a thorough histopathological analysis of their pancreatic tissues. RESULTS: The loss of Acvr1b increased the development of PanIN and IPMN-like lesions when either acinar and ductal cells expressed a Kras mutation. MRI, immunohistochemistry and histology revealed large IPMN-like lesions in these mice that exhibited features of flat, gastric epithelium. In addition, cyst formation in both mouse models was accompanied by chronic pancreatitis. Experimental acute pancreatitis accelerated the development of large mucinous cysts and PanIN when acinar, but not ductal, cells expressed mutant Kras and lost Acvr1b. CONCLUSION: These findings indicate that loss of Acvr1b in the presence of the Kras oncogene promotes the development of large and small precancerous lesions from both ductal and acinar cells. However, the IPMN-like phenotype was not equivalent to that observed when these mutations were made in all pancreatic cells during development. Our study underscores the significance of the cellular context in the initiation and progression of precursor lesions from exocrine cells.

Key target genes related to anti-breast cancer activity of ATRA: A network pharmacology, molecular docking and experimental investigation.

All-trans retinoic acid (ATRA) has promising activity against breast cancer. However, the exact mechanisms of ATRA's anticancer effects remain complex and not fully understood. In this study, a network pharmacology and molecular docking approach was applied to identify key target genes related to ATRA's anti-breast cancer activity. Gene/disease enrichment analysis for predicted ATRA targets was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), the Comparative Toxicogenomics Database (CTD), and the Gene Set Cancer Analysis (GSCA) database. Protein-Protein Interaction Network (PPIN) generation and analysis was conducted via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and cytoscape, respectively. Cancer-associated genes were evaluated using MyGeneVenn from the CTD. Differential expression analysis was conducted using the Tumor, Normal, and Metastatic (TNM) Plot tool and the Human Protein Atlas (HPA). The Glide docking program was used to predict ligand-protein binding. Treatment response predication and clinical profile assessment were performed using Receiver Operating Characteristic (ROC) Plotter and OncoDB databases, respectively. Cytotoxicity and gene expression were measured using MTT/fluorescent assays and Real-Time PCR, respectively. Molecular functions of ATRA targets (n = 209) included eicosanoid receptor activity and transcription factor activity. Some enriched pathways included inclusion body myositis and nuclear receptors pathways. Network analysis revealed 35 hub genes contributing to 3 modules, with 16 of them were associated with breast cancer. These genes were involved in apoptosis, cell cycle, androgen receptor pathway, and ESR-mediated signaling, among others. CCND1, ESR1, MMP9, MDM2, NCOA3, and RARA were significantly overexpressed in tumor samples. ATRA showed a high affinity towards CCND1/CDK4 and MMP9. CCND1, ESR1, and MDM2 were associated with poor treatment response and were downregulated after treatment of the breast cancer cell line with ATRA. CCND1 and ESR1 exhibited differential expression across breast cancer stages. Therefore, some part of ATRA's anti-breast cancer activity may be exerted through the CCND1/CDK4 complex.

Pancreatic carcinoma, its variants and precursors: Overview of the current WHO classification.

Pancreatic carcinoma is a relatively common malignant tumor with increasing incidence and mortality. The tumor is usually diagnosed at an advanced stage and generally has a poor prognosis, with only 5% of patients surviving 5 years from the time of diagnosis. The stage of the disease at the time of diagnosis is a crucial factor for the prognosis; 25% of patients with localized tumors survive 3 years from diagnosis, compared to only 1% of those with generalized tumors. Radical surgical removal of the tumor (partial or total pancreatectomy) is a key factor in improving survival. Therefore, the topic is highly relevant to surgeons. Statistics on pancreatic carcinoma mainly focus on ductal adenocarcinoma, which is the most common and least favorable malignant tumor of the pancreas. This review focuses on ductal adenocarcinoma, its variants, and precancerous lesions. The article summarizes information from the latest WHO classification of 2019, which was released 11 years after the previous edition. Compared to the previous version, this new WHO classification introduced rather minor changes in the field of ductal adenocarcinoma. The delineation of rare variants of ductal adenocarcinoma is justified based on genetic and morphological similarities and clinical relevance, as individual subtypes significantly differ in prognosis. The article also includes a description of macroscopic and microscopic precursors of ductal adenocarcinoma and their definitions. Genetic and immunohistochemical differential diagnostic aspects are briefly discussed, as these are more relevant to pathologists than to surgeons.

Multiple Endocrine Neoplasia Type 1, Type 2A, and Type 2B.

Multiple endocrine neoplasia type 1 is a rare genetic neuroendocrine syndrome caused by over 1500 different germline mutations. It can cause 20 different endocrine tumors affecting primarily the parathyroid glands, gastroenteropancreatic tract, and the anterior pituitary gland. Multiple endocrine neoplasia type 2A (MEN2A) and Multiple endocrine neoplasia type 2B (MEN2B) are autosomal dominant genetic syndromes because of a germline variant in the 'rearranged during transfection' (RET) proto-oncogene. There are common RET mutations causing receptor hyperactivation and induction of downstream signals that cause oncogenesis. Common conditions with MEN2A are medullary thyroid cancer (MTC), pheochromocytoma, and primary hyperparathyroidism. Common conditions with MEN2B include MTC, pheochromocytomas, and benign ganglioneuromas.

Comparison of bacterial culture results obtained from three different sampling locations in dogs and cats with chronic nasal disease.

AIMS: To assess agreement of bacterial culture results from samples taken from nasal discharge, the nasal cavity and nasal biopsy from dogs and cats with nasal disease. METHODS: Nineteen dogs and 21 cats with different nasal diseases (chronic rhinitis, n = 30; neoplasia, n = 7; sinonasal aspergillosis, n = 3) were prospectively enrolled in the study. Nasal swabs were taken bilaterally from nasal discharge at the nares, the nasal cavity, and one nasal mucosal biopsy per side. All samples were subjected to aerobic bacterial culture. Kappa statistics were used to evaluate agreement for the most prevalent bacterial species between sampling sites. RESULTS: A positive culture result for at least one bacterial species was detected in 80% of samples from nasal discharge/nares, 92% of nasal cavity samples, and 75% of biopsy samples. The mean agreement between the three sampling sites for positive vs. negative culture results was never greater than moderate and the precision of the estimates of agreement varied widely.The most frequently isolated bacterial species in dogs were Staphylococcus pseudintermedius, Staphylococcus spp. and Streptococcus spp. In cats, Pasteurella spp. and Staphylococcus felis were the bacterial species cultured most frequently.For the most prevalent cultured species, Staphylococcus spp., mean agreement between sites was never greater than fair and the precision again varied widely. CONCLUSION: This study indicates that bacterial culture results in feline and canine nasal disease are site-specific and there was no evidence from this study for consistency between sites within a patient for many bacterial species. Consequently, if bacterial culture results from nasal swabs are used to guide therapeutic antimicrobial choice, different treatments may be selected depending on the site of culture. As a consequence, there is no evidence from this study that nasal bacterial cultures should be recommended as a routine diagnostic measure.

Development of a risk scoring system for predicting advanced colorectal neoplasia within subcentimetric polyps: A population-based study.

OBJECTIVE: To determine a risk scoring system for predicting advanced colorectal neoplasia (ACN) within subcentimetric polyps in a large Asian population. METHODS: A retrospective study was conducted in Hong Kong SAR, China involving participants who underwent colonoscopy between 2008 and 2015. A random sample of 20 072 subjects were included as the derivation cohort to assess ACN-associated independent factors using logistic regression modeling. Another 8603 subjects formed a validation cohort. A risk scoring system was developed and its performance was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: The risk scores were assigned based on the following criteria: (a) patients who were admitted from inpatient colonoscopy (2.2) or not (1); (b) with three or more chronic diseases (hypertension, diabetes mellitus, hyperlipidemia, heart disease, or cancer) (1.7) or not (1); (c) anemia (1.3) or without anemia (1); (d) receiving aspirin (0.5) or not (1); (e) receiving other nonsteroidal anti-inflammatory drugs (0.3) or not (1); (f) male (1.2) or female gender (1); (g) age <55 (1), 55-64 (1.4), 65-69 (2), 70 years or above (2.2). ACN was more common in those with scores of 2.192 or higher, and they were classified as high risk (HR). The prevalence of ACN in the validation cohort was 13.28% and 3.56% in the HR and low-risk groups, respectively. In both the derivation and validation cohorts, AUROC of the risk-scoring model was 0.7138. CONCLUSION: Physicians are recommended to utilize this validated score for risk-stratification of patients having subcentimetric polyps.

Cellular Senescence in Germ Cell Neoplasia In Situ (GCNIS) and Other Histological Types of Testicular Cancer.

Background and Objectives: The presence and contribution of senescent cells in premalignant lesions is well documented, but not in germ cell neoplasia in situ. The purpose of this study is to identify the presence of senescent cells in pre-malignant testicular conditions and in different histological types of testicular cancer. Materials and Methods: Thirty patients who underwent orchiectomy due to testicular tumors were included. Formalin-fixed paraffin-embedded (FFPE) testicular tissue for each patient was available. Sections from these specimens were examined by immunohistochemical analysis with the following markers: GL13 for cellular senescence, p21WAF1/Cip1 for cell cycle arrest, and Ki67 for cell proliferation. Results: Thirteen (43.3%) suffered from seminoma with a mean total proportion of GCNIS senescence of 20.81 ± 6.81%. In the group of embryonal testicular tumors, nine (30%) patients were included, with an average rate of 6.64 ± 5.42% of senescent cells in GCNIS. One (3.3%) patient suffered from chondrosarcoma in which 7.9% of GL13+ cells were detected in GCNIS. Four (13.4%) patients suffered from teratoma and three (10%) from yolk sac tumors, while GCNIS senescence was detected in a range of 4.43 ± 1.78% and 3.76 ± 1.37%, respectively. Conclusions: Cellular senescence was detected in both germ cell neoplasia in situ and testicular cancer, but was more prevalent within the premalignant lesions.

Pancreatic stellate cells and the interleukin family: Linking fibrosis and immunity to pancreatic ductal adenocarcinoma (Review).

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive form of cancer with a low survival rate. A successful treatment strategy should not be limited to targeting cancer cells alone, but should adopt a more comprehensive approach, taking into account other influential factors. These include the extracellular matrix (ECM) and immune microenvironment, both of which are integral components of the tumor microenvironment. The present review describes the roles of pancreatic stellate cells, differentiated cancer­associated fibroblasts and the interleukin family, either independently or in combination, in the progression of precursor lesions in pancreatic intraepithelial neoplasia and PDAC. These elements contribute to ECM deposition and immunosuppression in PDAC. Therapeutic strategies that integrate interleukin and/or stromal blockade for PDAC immunomodulation and fibrogenesis have yielded inconsistent results. A deeper comprehension of the intricate interplay between fibrosis, and immune responses could pave the way for more effective treatment targets, by elucidating the mechanisms and causes of ECM fibrosis during PDAC progression.