Nuclear features of papillary thyroid carcinoma: Comparison of Core needle biopsy and thyroidectomy specimens.

BACKGROUND: Core needle biopsy (CNB) has been used as an alternative or a complementary method for diagnosis of thyroid nodules. However, morphological analysis of the nuclear features of papillary thyroid carcinoma (PTC) cells obtained via CNB remains unclear. Hence, we examined the differences between the PTC nuclear features in CNB and thyroidectomy specimens. METHODS: Ten PTC patients, who underwent both CNB and thyroidectomy, were selected. Microscopic photographs of three representative areas of the PTC and adjacent parenchyma were taken. Ten cells per photograph were chosen, and 1200 cells were evaluated (300 PTC and 300 follicular cells in the CNB and thyroidectomy specimens, respectively). The area, circumference, major axis, and minor axis were measured using an image analyzer. Detailed nuclear features (size and shape, membrane irregularity, chromatin characteristics) were scored using a 3-point scale. RESULTS: The mean nuclear area, circumference, major axis, and minor axis of PTC cells in the CNB specimen were 1.76, 1.34, 1.34, and 1.29 times larger than those of the follicular cells (p<0.001); similar results were seen in the thyroidectomy specimens (2.04, 1.41, 1.37, and 1.37: p<0.001). Comparative analysis revealed that these parameters were significantly smaller in the CNB specimens than those in the thyroidectomy specimens (p<0.001). Nuclear grades were also lower in the former owing to poor chromatin characteristics (clearing and margination) (p<0.01). CONCLUSION: Considering that the PTC nuclei in CNB specimens are smaller with fewer irregularities and less clear than those in thyroidectomy specimens, we need to emphasize caution when using CNB specimens for diagnosis.

Plasmon Enhanced Fluorescence Based on Porphyrin-Peptoid Hybridized Gold Nanoparticle Platform.

A porphyrin-peptoid-hybridized silica-coated gold nanoparticle is developed, which is inspired by the protein-chlorophyll ensemble found in photosynthetic antenna. In the natural antenna, chlorophylls are integrated into dense assemblies that are supported by frameworks of proteins, which ensure optimal pigment arrangement for effective light harvesting. In the subject platform, porphyrins are conjugated to the peptoid helix scaffold in a structurally well-defined alignments and subsequently immobilized on the surface of nanoparticles. This prevents intermolecular aggregation among porphyrins and allows high resolution analysis of the effect of porphyrin configuration on the optical properties of the system. Interestingly, under the influence of plasmon from the gold nanoparticle core, the fluorescence of porphyrin is enhanced up to 24-fold at the wavelength where the plasmon resonance matches the porphyrin excitation wavelength. In addition, differences in porphyrin configuration result in spectral modification of their fluorescence emissions. Particularly, the peptoid bearing two porphyrins at a distance of 6 Å shows the most significant alteration in fluorescence. The platform can facilitate extensive studies on the relationship between porphyrin arrangement design and their photophysical interaction in antenna complexes.

Expression of ß-tubulin isotypes in urothelial carcinoma of the bladder.

PURPOSE: Our study aims to investigate the expressions of ß-tubulin isotypes and their significances in urothelial carcinoma of the bladder (UCB) as altered expression of a specific ß-tubulin isotype is associated with chemoresistance and poor prognosis in other malignancies. MATERIALS AND METHODS: Expression of ß-tubulin isotypes was retrospectively examined in 342 UCB samples obtained from 1995 to 2010 by immunohistochemistry. RESULTS: TUBB1 (307/342, 89.8 %) was most frequently overexpressed in the cytoplasm of UCB cases, followed by TUBB4 (101/342, 29.5 %), TUBB2 (85/342, 24.9 %), and TUBB3 (60/342, 17.5 %). TUBB1 overexpression was associated with older age (p = 0.032), high WHO grade (p = 0.001), and advanced TNM stage (p = 0.006). High levels of TUBB2 expression were associated with high WHO grade (p < 0.001), advanced TNM stage (p < 0.001), and non-papillary growth pattern (p = 0.007). TUBB3 overexpression was related to high WHO grade (p = 0.029). In univariate and multivariate survival analyses, TUBB1 overexpression was associated with poor recurrence-free survival (RFS) rates of all cases (hazard ratio 1.98, p = 0.031) and of the patients with transurethral and/or partial resection (hazard ratio 2.12, p = 0.031). TUBB2 overexpression was correlated with a short RFS of the patients with T2-T4 stages (hazard ratio 3.48, p = 0.007). TUBB3 overexpression was related to a poor RFS of the patients undergoing radical cystectomy (hazard ratio 5.90, p = 0.002). CONCLUSIONS: High TUBB1, TUBB2, and TUBB3 expressions are associated with unfavorable clinicopathologic factors and are independent prognostic factors for recurrence-free survival of UCB.

MAD2 and CDC20 are upregulated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix.

Abnormal expression of the spindle assembly checkpoint proteins causes tumor cell aneuploidy, which has been reported in various malignancies. The expression of mitotic arrest deficient 2 (MAD2) and cell-division cycle 20 homolog (CDC20), the key spindle assembly checkpoint proteins, has not been studied in cervical carcinogenesis. In this study, we compared the expression of MAD2 and CDC20 in 332 cases, including normal cervical tissues, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and invasive squamous cell carcinomas (SCCs). Both MAD2 and CDC20 were overexpressed in the nuclei or cytoplasm of dysplastic and malignant tumor cells. The frequency of MAD2 overexpression was markedly increased from undetectable (0/100) in normal cervical tissues and 2% (1/50) in low-grade squamous intraepithelial lesions to 67.1% (53/79) in HSILs and 52.4% (54/103) in SCCs. Similarly, CDC20 was overexpressed in 49.4% (39/79) of HSILs and 22.3% (23/103) of SCCs, whereas CDC20 was not detectable (0/100) in normal cervical tissues and overexpressed only in 8.0% (4/50) of low-grade squamous intraepithelial lesions. In SCC cases, MAD2 overexpression correlated with a patient age of less than 60 yr (P=0.043), nonkeratinizing histologic type (P=0.018), and a lesser degree of stromal invasion (P=0.026). In conclusion, MAD2 and CDC20 overexpression was increased in HSILs and SCCs, suggesting their involvement in the initiation of cervical cancers. Controlling CDC20 and MAD2 expression may be a therapeutic strategy for cervical cancer.

Hybrid system of semiconductor and photosynthetic protein.

Photosynthetic protein has the potential to be a new attractive material for solar energy absorption and conversion. The development of semiconductor/photosynthetic protein hybrids is an example of recent progress toward efficient, clean and nanostructured photoelectric systems. In the review, two biohybrid systems interacting through different communicating methods are addressed: (1) a photosynthetic protein immobilized semiconductor electrode operating via electron transfer and (2) a hybrid of semiconductor quantum dots and photosynthetic protein operating via energy transfer. The proper selection of materials and functional and structural modification of the components and optimal conjugation between them are the main issues discussed in the review. In conclusion, we propose the direction of future biohybrid systems for solar energy conversion systems, optical biosensors and photoelectric devices.

Comparing clinical outcomes of vitamin K antagonists vs non-vitamin K antagonists in anticoagulant therapy for mesenteric venous thrombosis.

OBJECTIVE: Non-vitamin K antagonist oral anticoagulants have shown similar efficacy and lower bleeding rates than vitamin K antagonists for venous thromboembolism. However, this has not been proven in mesenteric vein thrombosis. This study aimed to compare the clinical outcomes of vitamin K antagonists and non-vitamin K antagonist oral anticoagulants. METHODS: Between January 2014 and July 2022, mesenteric vein thrombosis was diagnosed on computed tomography in 225 patients in a tertiary hospital. Among them, a total of 44 patients who underwent long-term anticoagulation therapy over 3 months were enrolled in this study. Patients were divided into two groups based on the anticoagulant used: vitamin K antagonists (Group 1, n = 21) and non-vitamin K antagonist oral anticoagulants (Group 2, n = 23). The efficacy outcomes were symptom recurrence and thrombus resolution on follow-up computed tomography, and the safety outcome was bleeding complications. RESULTS: The median age of the patients was 56 years (range, 46-68 years), and 52% were men. The most common risk factors were unprovoked intra-abdominal infections (30%). The median duration of anticoagulation therapy was 13 months (20 months in Group 1 vs 6 months in Group 2; P = .076). Of the 44 patients, 17 (39%) received the standard treatment. The median follow-up period was longer in Group 1 than in Group 2 (57 vs 28 months; P = .048). No recurrence of mesenteric vein thrombosis-related symptoms were observed in either group. The median duration of follow-up computed tomography was 31 months (42 months in Group 1 vs 18 months in Group 2; P = .064). Computed tomography revealed complete thrombus resolution, partial resolution, and no changes in 71%, 19%, and 10%, respectively (P = .075). Regarding bleeding complications, varix bleeding and melena developed in two patients in Group 2, and anticoagulation treatment thereafter ceased. CONCLUSIONS: Despite the short follow-up duration in the non-vitamin K antagonist oral anticoagulants group, there was no clinically significant difference in the thrombus resolution rate or bleeding complications when compared with the vitamin K antagonists group. Although research on the long-term effects of non-vitamin K antagonist oral anticoagulants in patients is limited, non-vitamin K antagonist oral anticoagulants can be considered an alternative to conventional treatments.

Optimum tacrolimus trough levels for enhanced graft survival and safety in kidney transplantation: a retrospective multicenter real-world evidence study.

BACKGROUND: The current study aimed to determine the optimal tacrolimus trough levels for balancing graft survival and patient safety following kidney transplantation. MATERIALS AND METHODS: We conducted a retrospective cohort study involving 11,868 kidney transplant recipients from five medical centers. The association between tacrolimus exposures (periodic mean trough level, coefficient of variability, time in therapeutic range) and composite allograft outcome (de novo donor specific antibody, biopsy-proven rejection, kidney dysfunction, and graft failure), as well as safety outcomes (severe infection, cardiovascular events, malignancy, and mortality) were assessed. Data were sourced from Clinical Data Warehouses and analyzed using advanced statistical methods, including Cox marginal structural models with inverse probability treatment weighting. RESULTS: Tacrolimus levels of 5.0-7.9 ng/mL and 5.0-6.9 ng/mL during the 2-12 month and 12-72 month post-transplantation periods, respectively, were associated with reduced risks of composite allograft outcomes. During the first post-transplant year, the adjusted hazard ratios (aHR) for composite allograft outcomes were: 0.69 (95% CI 0.55-0.85, P<0.001) for 5.0-5.9 ng/mL; 0.81 (95% CI 0.67-0.98, P=0.033) for 6.0-6.9 ng/mL; and 0.73 (95% CI 0.60-0.89, P=0.002) for 7.0-7.9 ng/mL (compared to levels ≥8.0 ng/mL). For the 6-year composite outcomes, aHRs were 0.68 (95% CI 0.53-0.87, P=0.002) for 5.0-5.9 ng/mL and 0.65 (95% CI 0.50-0.85, P=0.001) for 6.0-6.9 ng/mL. These optimal ranges showed reduced rates of severe infection (6 y), malignancy (6 y), and mortality (1 y). CONCLUSION: This multicenter study provides robust evidence for optimal tacrolimus trough levels during the periods 2-12 and 12-72 months following kidney transplantation.

CD74 expression is increased in high-grade, invasive urothelial carcinoma of the bladder.

This study aimed to identify the clinicopathological features of bladder cancer patients with high CD74 expression, as milatuzumab humanized anti-CD74 antibody is being evaluated in clinical trials for hematological malignancies. Expression of CD74 was examined in 342 urothelial carcinomas of the bladder, and two urothelial carcinoma cell lines by immunohistochemistry and western blotting, respectively. CD74 was overexpressed in 192 (56.1%) of the 342 cancer tissues, although it was not expressed in the cancer cell lines. CD74 staining was intense in tumor cells and inflammatory cells in the tumor stroma, but not in normal urothelium. CD74 expression was significantly associated with older age at diagnosis (≥ 68 years, P=0.048), high World Health Organization grade (P=0.019), advanced stages (P=0.001) and non-papillary growth pattern (P=0.040). CD74 expression was also correlated with the absence of tumor-infiltrating inflammatory cells (P<0.001) and the presence of tumor-associated inflammatory cells (P=0.017). However, CD74 expression was not related to recurrence-free and overall survivals in primary and subgroup analyses. In conclusion, urothelial bladder carcinomas with high CD74 expression are characterized by older age, high World Health Organization grade, non-papillary growth and advanced stages.

Below-Knee Prosthetic Bypass Is a Viable Option for Limb Salvage in Patients with Extensive Femoropopliteal Occlusive Disease.

Purpose: This study aimed to (1) evaluate the outcomes of below-knee prosthetic bypass (BKPB) in the absence of the great saphenous vein, and (2) identify risk factors associated with these outcomes. Materials and Methods: This study included 37 consecutive patients who underwent BKPB with or without distal modification between 2010 and 2022. We further assessed the following treatment outcomes: primary patency (PP), secondary patency (SP), limb salvage (LS), and amputation-free survival (AFS) rates. The risk factors for PP were also examined. Results: Most patients (n=31) were male. In 32 (86.5%) patients, BKPBs were performed for chronic limb-threatening ischemia. At the time of initial admission, two (5.4%) early deaths and three (8.1%) major amputations were noted. At 1 year after BKPB, the overall PP, SP, LS, and AFS rates were 78%, 85%, 85%, and 70%, respectively; at 3 years, they were 58%, 70%, 80%, and 52%, respectively; and at 5 years, they were 35%, 58%, 62%, and 29%, respectively. Notably, PP was significantly lower in limbs with ≤1 patent tibial arteries than in limbs with ≥2 patent artery (hazard ratio [HR], 3.80; 95% confidence interval [CI], 1.14-12.69 for overall; and HR, 12.97; 95% CI, 2.15-78.08 for distal anastomosis to below-knee popliteal artery). However, the PP was unaffected by the distal modification. Conclusion: BKPB is a viable option for LS in patients with extensive femoropopliteal disease. Tibial runoff was significantly correlated with patency; therefore, decision-making for BKPB and follow-up must involve careful evaluation of the outflow arteries.

A Rare Granular Cell Tumor with a Center Ulcer of the Rectum.

We report a very rare case of granular cell tumor with a center ulcer of the rectum, which was detected in a 47-year-old man during screening colonoscopy. It is difficult to distinguish granular cell tumor from other subepithelial tumors. However, our case had a center ulcer unlike previous cases. We confirmed the diagnosis using histological and immunohistochemical examinations. In addition to our case report, we discuss the morphology, size, layer of invasion, and treatment of rectal granular cell tumors based on a literature review.

Electrochemical ß-Selective Hydrocarboxylation of Styrene Using CO2 and Water.

The carboxylation of hydrocarbons using CO2 as a one-carbon building block is an attractive route for the synthesis of carboxylic acids and their derivatives. Until now, chemical carboxylation catalyzed by organometallic nucleophiles and reductants has been generally adopted particularly for the precise selectivity control of carboxylation sites. As another approach, electrochemical carboxylation has been attempted but these carboxylation reactions are limited to only a few pathways. In the case of styrene, dicarboxylation at the α- and ß-positions is mostly observed with electrochemical carboxylation while site-selective hydrocarboxylations are hardly achieved. In this study, electrochemical ß-selective hydrocarboxylation of styrene using CO2 and water is developed, in which the site selectivity can be precisely controlled between ß-hydrocarboxylation and dicarboxylation without the aid of homogeneous catalysts. In this platform, water is used as proton source in the ß-hydrocarboxylation of styrene where its addition results in significant enhancement of the selectivity toward ß-hydrocarboxylation. This work provides insights into new strategies for site-selectivity-controllable carboxylation with CO2 using an electrochemical platform.

An Implantable Ionic Wireless Power Transfer System Facilitating Electrosynthesis.

A number of implantable biomedical devices have been developed, and wireless power transfer (WPT) systems are emerging as a way to provide power to these devices without requiring a hardwired connection. Most of the WPT has been based on conventional conductive materials, such as metals, which tend to be less biocompatible and stiff. Herein, we describe a development of an ionic wireless power transfer (IWPT) system using hydrogel receivers that are soft and biocompatible. Although the hydrogel receiver has a lower conductivity than metal (ρgel/ρmetal ∼ 10-7), a capacitive coupling between receiver and transmitter enables the IWPT to deliver 4 mA of current at its resonance frequency. The capacitive coupling through the dielectric and the electrolyte was analyzed including a parasitic effect, and the IWPT was applied to implantable devices to transfer power via the skin. The IWPT system was further developed to facilitate electrosynthesis. Generation of nicotinamide adenine dinucleotide phosphate, a reducing agent in metabolism, was demonstrated by IWPT to show its potential for electrosynthesis.

Traumatic neuroma of remnant cystic duct mimicking duodenal subepithelial tumor: A case report.

BACKGROUND: Gastrointestinal subepithelial tumors (GSTs), incidentally detected during upper gastrointestinal (GI) endoscopy, may be lesions derived from the GI wall or may be caused by compression from external organs. In general, traumatic neuroma is a benign nerve tumor that results from postoperative nerve injury, occurring in the bile duct as one of the complications after cholecystectomy. This is the first case report demonstrating that neuroma of the cystic duct can be incorrectly perceived as a duodenal subepithelial tumor by compressing the duodenal wall. CASE SUMMARY: We report the case of a 72-year-old man with traumatic neuroma of the cystic duct after cholecystectomy. This tumor was mistaken for a duodenal subepithelial tumor on preoperative upper GI endoscopy and endoscopic ultrasonography due to external compression of the GI wall. The patient had no symptoms, and his laboratory test results were normal. However, in a series of follow-up endoscopies, the tumor was found to have grown in size, so it was surgically resected. The lesion was completely removed by laparoscopic endoscopic cooperative surgery. The patient was discharged on postoperative day 7 without complications. CONCLUSION: Traumatic neuroma of the cystic duct can be mistaken for GSTs in GI endoscopy.

Spindle assembly checkpoint MAD2 and CDC20 overexpressions and cell-in-cell formation in gastric cancer and its precursor lesions.

Overexpression of mitotic arrest deficient 2 (MAD2) and/or cell division cycle 20 (CDC20) in the spindle assembly checkpoint leads to chromosomal instability and aneuploidy. Cell-in-cell (CIC) structures are formed by the process where cancer or immune cells are internalized into adjacent host cancer cells. Here, we investigated the clinicopathological significances of spindle assembly checkpoint protein overexpression and CIC structures in 829 cases of normal, premalignant, and gastric cancer (GC) lesions. MAD2 and CDC20 expressions were significantly increased in intestinal metaplasia, low-grade dysplasia, high-grade dysplasia (HGD), and early GC than normal mucosa, and their expression levels were the highest in HGD. Interestingly, CDC20 immunohistochemistry specifically stained the outer cells of CIC structures, which were the most frequently observed in early GC. In univariate analyses, MAD2 and CDC20 overexpressions and CIC formation were associated with older age, intestinal histology, lower tumor-node-metastasis stage, and longer recurrence-free survival and cancer-specific survival of GC patients. In multivariate survival analyses, MAD2 and CDC20 overexpressions were associated with better recurrence-free survival (hazard ratio, 0.61; P = .012) and cancer-specific survival (hazard ratio, 0.63; P = .043), respectively. In conclusion, MAD2 and CDC20 are the most expressed in HGD, suggesting their roles in the early stage of gastric carcinogenesis, whereas their overexpressions in GC are associated with intestinal histology and favorable clinicopathological parameters, which may be useful for immunohistochemical classification of chromosomal instability-type GC. Moreover, CDC20 is a novel immunohistochemical marker for highlighting CIC structures.

Tyrosine-Rich Peptides as a Platform for Assembly and Material Synthesis.

The self-assembly of biomolecules can provide a new approach for the design of functional systems with a diverse range of hierarchical nanoarchitectures and atomically defined structures. In this regard, peptides, particularly short peptides, are attractive building blocks because of their ease of establishing structure-property relationships, their productive synthesis, and the possibility of their hybridization with other motifs. Several assembling peptides, such as ionic-complementary peptides, cyclic peptides, peptide amphiphiles, the Fmoc-peptide, and aromatic dipeptides, are widely studied. Recently, studies on material synthesis and the application of tyrosine-rich short peptide-based systems have demonstrated that tyrosine units serve as not only excellent assembly motifs but also multifunctional templates. Tyrosine has a phenolic functional group that contributes to π-π interactions for conformation control and efficient charge transport by proton-coupled electron-transfer reactions in natural systems. Here, the critical roles of the tyrosine motif with respect to its electrochemical, chemical, and structural properties are discussed and recent discoveries and advances made in tyrosine-rich short peptide systems from self-assembled structures to peptide/inorganic hybrid materials are highlighted. A brief account of the opportunities in design optimization and the applications of tyrosine peptide-based biomimetic materials is included.

IFNγ induces PD-L1 overexpression by JAK2/STAT1/IRF-1 signaling in EBV-positive gastric carcinoma.

Programmed death-ligand 1 (PD-L1) acts as an immune checkpoint inhibitor in various cancers. PD-L1 is known to be more frequently expressed in EBV (+) gastric cancer (GC). However, the mechanisms underlying the regulation of PD-L1 expression in EBV (+) GC remain unclear. We investigated the basal and inducible PD-L1 expressions in GC cells. PD-L1 expression was upregulated upon treatment with IFNγ in both EBV (-) and EBV (+) GC cells. Upon stimulation with the same concentration of IFNγ for 24 h, EBV (+) SNU-719 cells showed dramatically higher PD-L1 expression levels by activating JAK2/STAT1/IRF-1 signaling than those of EBV (-) AGS cells. PD-L1 promoter assays, chromatin immunoprecipitation, and electrophoretic mobility shift assays revealed that IFNγ-inducible PD-L1 overexpression is primarily mediated by the putative IRF-1α site of the PD-L1 promoter in EBV (+) SNU-719 cells. Moreover, EBNA1 knockdown reduced both constitutive and IFNγ-inducible PD-L1 promoter activity by decreasing the transcript and protein levels of JAK2 and subsequently STAT1/IRF-1/PD-L1 signaling. EBNA1 is suggested to be moderately enhance both constitutive and IFNγ-inducible PD-L1 expression in EBV (+) GC cells. Thus, the signaling proteins and EBNA1 that regulate PD-L1 expression are potential therapeutic targets in EBV (+) GC.

[Task analysis of Korean geriatric care managers].

PURPOSE: This study was designed to create a job description for Korean geriatric care managers and examine performance frequency, importance, and difficulty of task elements. METHOD: The sample consisted of 38 geriatric care managers and professors who performed duties related to geriatric care management at community based-facilities in Korea. A survey method was used, and the questionnaire included frequency, importance, and difficulty of task elements in job descriptions using the DACUM method. Using SPSS WIN 10.0, descriptive statistics such as frequency distribution, means, and standard deviation were conducted to examine the subject's general characteristics, frequency, importance, and difficulties of task performance. RESULT: The job description of geriatric care managers revealed 10 duties, 34 tasks, and 105 task elements. On all ten duties, the average performance frequency, importance, and difficulty was 2.55, 2.21 and 2.43 respectively. CONCLUSION: The job description of geriatric care managers includes duty, task, and task elements and the definition of a completed job. Thus we recommend a data based trial to confirm and validate the information gathered.

The clinical performance of primary HPV screening, primary HPV screening plus cytology cotesting, and cytology alone at a tertiary care hospital.

BACKGROUND: Algorithms for primary human papillomavirus (HPV) screening, primary HPV screening plus cytology cotesting, and cytology alone were evaluated previously in large cohort trials for cervical cancer detection, although the quality of cytology in those studies was controversial. To investigate whether these 3 algorithms would be applicable in routine practice at a tertiary care hospital, the authors compared their clinical performance. In addition, the prevalence of HPV genotypes was determined. METHODS: Cervical cytology samples (n = 1000) were tested using liquid-based cytology (LBC), a nucleic acid hybridization assay, real-time polymerase chain reaction analysis, and direct HPV DNA sequencing. The clinical performance of the 3 algorithms was compared among women in different age groups (age range, 17-86 years; median age, 44.7 years). RESULTS: For cervical intraepithelial neoplasia grade 2 or worse (CIN 2+), the sensitivity of primary HPV screening alone, cotesting, and LBC alone was 71.7%, 72.5%, and 63.8%, respectively; whereas the specificity was 87.5%, 96.5%, and 97.4%, respectively. Cotesting and LBC alone had slightly higher positive predictive values for CIN 2 + (97.8% and 98.9%, respectively) than primary HPV screening alone (91%), whereas primary HPV screening alone and cotesting demonstrated higher negative predictive values (63.6% and 62.5%, respectively) than LBC alone (43.2%). High-risk HPV types were detected in 24.3% of individuals. The most common type was HPV type 16 (HPV-16) followed by multiple HPV infections and HPV-58, HPV-52, HPV-31, HPV-35, HPV-51, HPV-39, HPV-56, HPV-33, HPV-18, HPV-59, and HPV-45. CONCLUSIONS: Primary HPV screening alone in a tertiary care hospital demonstrated a performance that was equivalent to that of cotesting for CIN 2+, irrespective of patient age. With regard to the distribution of HPV genotypes, the nonavalent HPV vaccine would prevent approximately 60% of high-risk HPV.

KRAS, GNAS, and RNF43 mutations in intraductal papillary mucinous neoplasm of the pancreas: a meta-analysis.

BACKGROUND: The prevalence and clinical significances of KRAS, GNAS, and RNF43 mutations in patients with pancreatic intraductal papillary mucinous neoplasm (IPMN) remain elusive. To evaluate the incidence of the gene mutations and clinicopathologic differences between KRAS and GNAS mutations in pancreatic cystic lesions, we performed a meta-analysis of published 33 KRAS, 11 GNAS, and 4 RNF43 studies including 1253, 835, and 143 cases, respectively. METHODS: We pooled the results of relevant studies identified using the PubMed and EMBASE databases. The effect sizes of outcome parameters were computed by the prevalence rate, weighted mean difference, or odds ratio (OR) using a random-effects model. RESULTS: The pooled prevalence of KRAS, GNAS, and RNF43 mutations in IPMN was 61, 56, and 23 %, respectively. The KRAS (OR 7.4 and 71.2) and GNAS (OR 30.2 and 15.3) mutations were more frequently found in IPMNs than in mucinous cystic neoplasms and in serous cystadenomas, respectively. Of the microscopic subtypes of IPMN, KRAS and GNAS were frequently mutated in gastric type (OR 2.7, P < 0.001) and intestinal type (OR 3.0, P < 0.001), respectively. KRAS mutation was infrequently found in high-grade dysplasia lesions of IPMN (OR 0.6, P = 0.032). GNAS mutation was associated with male (OR 1.9, P = 0.012). CONCLUSIONS: This meta-analysis supports that KRAS and GNAS mutations could be diagnostic markers for IPMN. In addition, the frequencies of KRAS and GNAS mutations in IPMNs are highly variable according to the microscopic duct subtypes, reflecting their independent roles in the IPMN-adenocarcinoma sequence.