A novel class of antimicrobial drugs selectively targets a Mycobacterium tuberculosis PE-PGRS protein.

The continued spread of drug-resistant tuberculosis is one of the most pressing and complex challenges facing tuberculosis management worldwide. Therefore, developing a new class of drugs is necessary and urgently needed to cope with the increasing threat of drug-resistant tuberculosis. This study aims to discover a potential new class of tuberculosis drug candidates different from existing tuberculosis drugs. By screening a library of compounds, methyl (S)-1-((3-alkoxy-6,7-dimethoxyphenanthren-9-yl)methyl)-5-oxopyrrolidine-2-carboxylate (PP) derivatives with antitubercular activity were discovered. MIC ranges for PP1S, PP2S, and PP3S against clinically isolated drug-resistant Mycobacterium tuberculosis strains were 0.78 to 3.13, 0.19 to 1.56, and 0.78 to 6.25 µg/ml, respectively. PPs demonstrated antitubercular activities in macrophage and tuberculosis mouse models, showing no detectable toxicity in all assays tested. PPs specifically inhibited M. tuberculosis without significantly changing the intestinal microbiome in mice. Mutants selected in vitro suggest that the drug targets the PE-PGRS57, which has been found only in the genomes of the M. tuberculosis complex, highlighting the specificity and safety potency of this compound. As PPs show an excellent safety profile and highly selective toxicity specific to M. tuberculosis, PPs are considered a promising new candidate for the treatment of drug-resistant tuberculosis while maintaining microbiome homeostasis.

Clinical utility of methionyl-tRNA synthetase 1 immunostaining in cytologic brushings of indeterminate biliary strictures: a multicenter prospective study.

BACKGROUND AND AIMS: Endobiliary brushings are routinely used in the diagnosis, treatment, and prognostication of biliary strictures. However, standard Papanicolaou (Pap) staining has a low sensitivity in this setting, and the accuracy of brush cytology has not been established for indeterminate strictures. We therefore evaluated the diagnostic merit of methionyl-transfer RNA synthetase 1 (MARS1) immunofluorescence (IF) staining in such cytologic specimens. METHODS: During ERCP, endobiliary brushings were obtained from patients with extrahepatic biliary strictures prospectively enrolled at 6 tertiary hospitals. Using liquid-based cytologic preparations of these samples, we performed Pap and MARS1 IF staining. RESULTS: In total, 240 patients were eligible; of these, we compared the Pap and MARS1 IF staining results of 218 (malignant, 157; benign, 61). By conventional Pap staining, the diagnoses were distributed as follows: malignant, 55; suspicious of malignancy, 60; atypical, 45; negative for malignancy, 58. MARS1 IF staining was strongly positive in malignant biliary stricture but not so in specimens negative for malignancy. The diagnostic parameters (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) of the MARS1 IF (93.6%, 96.7%, 98.7%, 85.5%, and 94.5%, respectively) and conventional Pap (73.2%, 100%, 100%, 59.2%, and 80.7%, respectively) staining methods differed significantly (P < .0001). CONCLUSIONS: The high sensitivity and accuracy of MARS1 IF staining enabled the detection of malignancy in patients with biliary strictures. Further prospective studies are needed to validate our findings. (Clinical trial registration number: NCT03708445.).

Efficacy of 3 fine-needle biopsy techniques for suspected pancreatic malignancies in the absence of an on-site cytopathologist.

BACKGROUND AND AIMS: EUS-guided fine-needle aspiration/biopsy (EUS-FNA/B) has a high diagnostic accuracy for pancreatic tumors. Most reports have focused on the diagnostic yield of cytology or histology; the ability of various FNA/B techniques to obtain an adequate mass of cells or tissue has rarely been investigated. METHODS: Patients with suspected pancreatic malignancy underwent EUS-FNB using a 22-gauge ProCore needle by either the stylet slow-pull-back technique (group A), conventional negative suction after stylet removal (group B), or non-suction after stylet removal (group C) in the absence of an on-site cytopathologist. The adequacy of the 3 techniques based on the diagnostic yield, cellularity, blood contamination, and core-tissue acquisition was evaluated. RESULTS: A total of 50 patients (27 males) were analyzed. The mean tumor size was 21 to 40 mm in 54%. The rate of a good or excellent proportion of cellularity was highest in group A compared with groups B and C (72% vs 60% vs 50%, P = .049). A >25% rate of blood contamination was more prevalent in group B (30% vs 42% vs 10%, P = .009). The rate of adequate core-tissue acquisition was not different (52% vs 34% vs 50%, P = .140). Based on the multivariate generalized estimation equation, the stylet slow-pull-back technique and a tumor size >40 mm were favorable factors for diagnostic adequacy. CONCLUSIONS: The stylet slow-pull-back technique might enable acquisition of tissue and assessment of cellularity for the diagnosis of pancreatic tumors suspected to be malignant. (Clinical trial registration number: KCT0002190.).

The relationship between local recurrence and positive lateral margin after en bloc resection of colorectal neoplasm.

BACKGROUND: The factors associated with recurrence of colonic neoplasm after endoscopic resection with a positive lateral margin are not well known. Thus, we evaluate the relationship between recurrence and positive lateral margin after endoscopic en bloc resection of colorectal neoplasm. METHODS: A retrospective review of 9302 patients who underwent colonic endoscopic resection from January 2008 to January 2015. Of these, a total of 76 patients with positive lateral margins with clear evidence of the its location on endoscopic picture after endoscopic en bloc resection of colorectal neoplasm (>10 mm) were included. RESULTS: Ten of 76 (13.2%) patients experienced recurrence during the follow-up period (mean f/u month, 21.7 ± 15.6). In cases with positive lateral margins, the 3- and 5-year local recurrence rate of colorectal neoplasm was 28.1% and 40.1%, respectively. The histological features of the recurrence group were as follows: one case of adenocarcinoma [from low-grade adenoma (LGA)]; two cases of high-grade adenoma (HGA) (one from HGA and one from LGA); and seven cases of LGA (four from adenocarcinoma, two from LGA, and one from HGA). The mean age of patients, locations of the lesions, and histologic type were not significantly associated with local recurrence. In multivariate Poisson regression analyses, total length of lateral margin involvement ≥8 mm (relative risk 12.51; 95% CI 1.11-140.34, p = .040) was a significant predictor of local recurrence. CONCLUSIONS: Positive lateral margins ≥8 mm may be a reliable predictor of local recurrence after endoscopic en bloc resection of colorectal neoplasm.

Clinical Effectiveness of Submucosal Injection with Indigo Carmine Mixed Solution for Colon Endoscopic Mucosal Resection.

BACKGROUND/AIMS: Submucosal injection with indigo carmine mixed solution can improve the delineation of colorectal neoplasia during endoscopic mucosal resection (EMR). Thus, the aim of this study was to evaluate the efficacy of submucosal injection with indigo carmine mixed solution during EMR of colorectal neoplasia. METHODS: This was a prospective, randomized, controlled study of a total of 212 neoplastic colon polyps (5-20 mm) subjected to EMR in a single tertiary university hospital. The patients were randomized into two groups according to whether or not indigo carmine mixed solution was used, and the complete resection rate (CRR) after EMR was evaluated. RESULTS: A total of 212 neoplastic polyps (normal saline group, 115; indigo carmine group, 97) were successfully removed by EMR. There was no significant difference in the CRR (92.8 vs. 89.6%, p = 0.414) or macroscopic delineation (86.0 vs. 93.8%, p = 0.118) between the two groups. In a separate analysis of sessile serrated adenomas/polyps (SSAs/Ps), macroscopic delineation was better in the indigo carmine group than the normal saline group (87.5 vs. 53.8%), albeit not significantly (p = 0.103). In univariate analyses, the CRR was significantly related to polyp location, polyp morphology, macroscopic delineation, and pathologic findings. In a multiple logistic regression analysis, macroscopic delineation (odds ratio (OR), 7.616, p = 0.001) and polyp pathology (OR, 8.621; p < 0.001) were significantly associated with the CRR. CONCLUSIONS: Submucosal injection with indigo carmine mixed solution did not improve the CRR or macroscopic delineation of EMR of colorectal neoplasias.

Thymoquinone (TQ) inhibits the replication of intracellular Mycobacterium tuberculosis in macrophages and modulates nitric oxide production.

BACKGROUND: Human tuberculosis, which is caused by the pathogen Mycobacterium tuberculosis, remains a major public health concern. Increasing drug resistance poses a threat of disease resurgence and continues to cause considerable mortality worldwide, which necessitates the development of new drugs with improved efficacy. Thymoquinone (TQ), an essential compound of Nigella sativa, was previously reported as an active anti-tuberculosis agent. METHODS: In this study, the effects of TQ on intracellular mycobacterial replication are examined in macrophages. In addition, its effect on mycobacteria-induced NO production and pro-inflammatory responses were investigated in Mycobacterium tuberculosis (MTB)-infected Type II human alveolar and human myeloid cell lines. RESULTS: TQ at concentrations ranging from 12.5 to 25 µg/mL and 6.25 to 12.5 µg/mL reduced intracellular M. tuberculosis H37Rv and extensively drug-resistant tuberculosis (XDR-TB) 72 h post-infection in RAW 264.7 cells. TQ treatment also produced a concentration-dependent reduction in nitric oxide production in both H37Rv and XDR-TB infected RAW 264.7 cells. Furthermore, TQ reduced the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory molecules such as tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6) in H37Rv-infected cells and eventually reduced pathogen-derived stress in host cells. CONCLUSIONS: TQ inhibits intracellular H37Rv and XDR-TB replication and MTB-induced production of NO and pro-inflammatory molecules. Therefore, along with its anti-inflammatory effects, TQ represents a prospective treatment option to combat Mycobacterium tuberculosis infection.

Late-onset metastatic adenocarcinoma of the spermatic cord from primary gastric cancer.

BACKGROUND: Metastatic cancers of the paratesticular tissue are very rare; however, the most frequent primary site of spermatic cord metastasis is the gastrointestinal tract. CASE PRESENTATION: We recently observed two cases of late-onset metastatic adenocarcinoma of the spermatic cord. Both patients complained of groin discomfort with a palpable mass in the scrotum and inguinal area. Radical orchiectomy and adjuvant chemotherapy were performed in both patients. Although the prognosis of patients with metastatic adenocarcinoma of the spermatic cord is typically poor, the prognosis of our patients was favorable after follow-up for 14 to 18 months. CONCLUSIONS: In patients with groin discomfort or swelling and a history of gastric cancer, metastatic adenocarcinoma should be included in the differential diagnosis for early detection of tumors.

Pathological Predictors for Defining a Therapeutic Strategy for Early Colon Cancer after Endoscopic Resection: Multicenter Retrospective Analysis from Surgically Resected Specimens.

BACKGROUND/AIMS: For the possibility of regional lymph node metastasis (LNM), early colon cancer (ECC) is a boundary lesion between endoscopic resection and surgery. The aim of study is to clarify risk factors for LNM and to determine therapeutic strategy after endoscopic resection in patients with ECC. METHODOLOGY: The histopathology of patients with ECC underwent surgery with LN dissection in 8 university hospitals were reviewed by experienced pathologist blinded to LN status. RESULTS: In total, 370 patients (107 with mucosal cancer, 263 with submucosal invasive colorectal carcinoma [SICC]) were enrolled. Excluding mucosal cancer, the LNM rate was 11.8% (31/263, including 15.4% [8/52] with pedunculated SICC [P-SICC] and 10.9% [23/211] with non-pedunculated SICC [NP-SICC]). Multivariate analysis showed that tumor sprouting (P < 0.001; odds ratio [OR], 8.83; 95% confidence interval [CI], 3.04-25.69), submucosal invasion depth (SM depth) > 2000 µm (P = 0.024; OR, 3.68; 95% CI, 1.19-11.37), and lymphatic invasion (P = 0.022; OR, 3.48; 95% CI, 1.19-10.13) were related to LNM. All LNMs with SM depth < 2000 µm showed tumor sprouting without lymphatic invasion. CONCLUSIONS: Significant risk factors for predicting LNM in patients with SICC were tumor sprouting, SM depth > 2000 µm, and lymphatic invasion.

Clinical analysis of an ultrasound system in the evaluation of skin cancers: correlation with histology.

BACKGROUND: The assessment of skin cancers in the clinical setting is often difficult, with important features such as depth and width remaining unknown until the biopsy with pathology reports are received. When we remove skin cancers, with those especially involving the face, aesthetics and invasion to surrounding structures such as bone and cartilage are important features for deciding the optimal surgical procedure and future reconstructive options. The aim of the study was to compare the accuracy of the ultrasound system in vivo and to correlate the results with the histopathological tumor thickness measured in skin cancer patients. PATIENTS AND METHODS: From March 2010 to February 2012, we reviewed 40 patients who comprised a total of 49 skin lesions involving the face, neck, and scalp. Each skin lesions were classified by 9 facial aesthetic units. The patient's various skin lesions were scanned using an ultrasound system device (Philips iU22 xMatrix US), with a 5-17-MHz compact linear transducer. Using the ultrasound system, we analyzed the shape, depth, echogenicity, size, invasion skin level, and vascularity of the skin cancer lesions. The results were correlated with the histology, with special note to the depth of involvement. RESULTS: Of the 40 patients recruited, 15 were male and 25 were female, ranging in age from 53 to 92 years (mean ± SD 78.7 ± 13.7 years). Clinically, 49 lesions suspicious of skin cancer were identified and ultrasounds were performed preoperatively. Depth was measured by ultrasound and histology. Mean ultrasound depth of skin lesion was 3.97 ± 3.15 mm (range 0.80-14.00), and it was found to be 4.04 ± 2.92 mm (range 1.00-14.00) based off of histology. There was excellent correlation (interclass correlation coefficient, 0.953) between the depth of the skin lesions measured histologically and by using the ultrasound. CONCLUSION: The ultrasound is not meant to replace histologic evaluations, but it can be used as another diagnostic tool to provide improved preoperative planning. It can be used as a noninvasive, easy, and low-cost screening method for various skin cancers, and provides valuable information such as lesion margins, shape, layers of involvement, and vascularity patterns.

BRAF (V600E) mutation analysis in papillary thyroid carcinomas by peptide nucleic acid clamp real-time PCR.

BACKGROUND: Activating somatic mutation of the BRAF (V600E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC) with a variable frequency (32-87%) in different series by different methods. The BRAF (V600E) mutation is associated with various clinicopathological parameters. The mutation is an important factor for the management of the PTC patients. The objective of this study was to detect the BRAF (V600E) mutation in PTCs by peptide nucleic acid (PNA) clamp real-time PCR and to analyze the results with clinicopathological parameters. METHODS: We performed genetic analysis of BRAF (V600E) by PNA clamp real-time PCR in 211 PTCs in Korea, stratified by clinicopathological parameters. RESULTS: The BRAF (V600E) mutation was detected in 90% of PTC cases, and it occurred significantly more often in female patients than in male patients (p = 0.001). The clinicopathological parameters of age, tumor size, and disease stage were not associated with the BRAF (V600E) mutation, while extrathyroid invasion (p = 0.031), lymph nodal metastasis (p = 0.002), and tumor multiplicity (p = 0.020) were. CONCLUSIONS: The prevalence (90%) of the BRAF (V600E) mutation in this study is the highest ever reported, confirming the key role of this mutation in PTC tumorigenesis. The BRAF (V600E) mutation was associated with aggressive clinical behaviors including extrathyroid invasion, lymph nodal metastasis and tumor multifocality. The PNA clamp real-time PCR method for the BRAF (V600E) mutation detection is sensitive and is applicable in a clinical setting.

Human applications of submucosal endoscopy under conscious sedation for pure natural orifice transluminal endoscopic surgery.

BACKGROUND: The submucosal endoscopy provide not only a reliable methods of access and closure for peritoneoscopy, but also an endoscopic working space for full-thickness resection. The aim of this study was to report the clinical outcome of submucosal endoscopy for pure natural orifice transluminal endoscopic surgery. METHODS: We prospectively evaluated 10 patients who received submucosal endoscopies. The indications of submucosal endoscopy were transgastric peritoneoscopy (TGP) and endoscopic full-thickness resection (EFTR) of a gastric subepithelial tumor. All procedures were performed with a standard gastroscope under conscious sedation with the balanced propofol method in the endoscopic unit. After a 40 mm submucosal tunnel was created using an endoscopic submucosal dissection technique, (1) in TGP, balloon dilation of a serosal puncture and intraperitoneal exploration was performed; (2) in EFTR, a full-thickness incision and snaring resection was performed. Closure of the mucosal incision was performed by endoclips. RESULTS: All cases were technically feasible. The mean times for creating the submucosal tunnel, main procedure (peritoneal exploration or resection), and closure were acceptable (10.44 ± 2.42 minutes, 18.80 ± 9.41 minutes, and 5.63 ± 2.17 minutes, respectively). The mean hospital stay was 3.8 ± 1.48 days. All TGPs were diagnostic (4 peritoneal carcinomatosis and 1 tuberculosis). En bloc and complete resections were possible in all EFTRs (3 gastrointestinal stromal tumors and 2 schwannomas; mean tumor size, 20.8 ± 3.27 mm). There were no procedure-related complications, such as significant bleeding or peritonitis. CONCLUSIONS: Human applications of submucosal endoscopy under conscious sedation for pure NOTES were feasible and safe.

Clinicopathological Significance of DUB3 Expression in Non-small Cell Lung Cancer and Relationship Between DUB3 Expression and LATS1 Expression.

BACKGROUND/AIM: Deubiquitinating enzyme 3 (DUB3) is a member of the ubiquitin-specific proteases family involved in regulating cell proliferation, invasion, and apoptosis. However, the biological role and clinicopathological significance of DUB3 expression have not been elucidated in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We evaluated the expression of DUB3 by immunohistochemistry using tissue microarrays and assessed the clinicopathologic significance of DUB3 expression levels in 187 patients with NSCLC, including its two major subtypes (93 cases of adenocarcinoma and 72 cases of squamous cell carcinoma). RESULTS: In adenocarcinoma, we observed that DUB3 expression had an effect on tumor size (p=0.030), vessel invasion (p=0.038), T stage (p=0.014), and tumor recurrence (p=0.002). Kaplan-Meier curves with log-rank test showed that high DUB3 expression was correlated with significantly more favorable clinical outcomes compared to those of the low expression group in adenocarcinoma (p=0.013). Multivariate analysis of disease-free survival also demonstrated that DUB3 expression is an independent prognostic factor in lung adenocarcinoma (p=0.017). Additionally, we identified the correlation between DUB3 and the expression of large tumor suppressor kinase 1 expression, a core protein of the Hippo pathway. CONCLUSION: DUB3 could function as a tumor suppressor by regulating the Hippo pathway in lung adenocarcinoma and can be considered a powerful predictive factor and therapeutic target.

Endoscopic partial resection with the unroofing technique for reliable tissue diagnosis of upper GI subepithelial tumors originating from the muscularis propria on EUS (with video).

BACKGROUND: There is a growing body of evidence that a pathological diagnosis is necessary for small (<3 cm in diameter), asymptomatic, hypoechoic, subepithelial tumors (SETs) originating from the muscularis propria on EUS. However, the diagnostic efficacy of current tissue sampling techniques appears to be limited. OBJECTIVE: To evaluate the diagnostic yield and safety of endoscopic partial resection using the unroofing technique (EPR-UT) in a subset of patients. DESIGN: A prospective case series. SETTING: A single tertiary-care referral center. PATIENTS: Between August 2007 and March 2009, 16 patients with hypoechoic SETs of <3 cm in diameter, originating from the muscularis propria on EUS (14 gastric and 2 esophageal lesions), underwent EPR-UT. INTERVENTIONS: The overlying mucosa was removed by using the unroofing technique using a conventional snare with electrical current to expose the tumor sufficiently. Next, the exposed tumor was partially resected by snaring. MAIN OUTCOME MEASUREMENTS: The diagnostic yield and safety of this method. RESULTS: EPR-UT provided specimens that were sufficient for a diagnosis and the assessment of risk for malignancy in 15 out of 16 cases (diagnostic yield 93.7% [95% CI, 80.4%-100.0%]). The pathological diagnoses were leiomyoma (7 of 15, 46.6%), GI stromal tumor (6 of 15, 40.0%), aberrant pancreas (1 of 15, 6.6%), and well-differentiated neuroendocrine carcinoma (1 of 15, 6.6%). Six cases with GI stromal tumor were classified as very low risk for malignant potential (mitotic index <5/50 high-power fields). Procedural blood oozing was relatively common (9 of 16, 56.0% [95% CI, 33.0%-77.0%]); however, this minor complication was easily controlled by argon plasma coagulation. There were no procedure-related major complications (0 of 16, 0% [95% CI, 0.0%-23.0%]). LIMITATIONS: Single-center, noncomparative study with small sample size. CONCLUSION: EPR-UT appears to be simple, safe, and effective for determining the definite pathological diagnosis and assessing malignant potential of small, hypoechoic SETs originating from the muscularis propria on EUS.

Is endoscopic forceps biopsy enough for a definitive diagnosis of gastric epithelial neoplasia?

BACKGROUND AND AIM: Endoscopic forceps biopsy (EFB) as the primary histological diagnosis of gastric epithelial neoplasia (GEN) is debated in the era of endoscopic resection (ER). Our aim was to investigate the diagnostic reliability of EFB in patients with GEN compared with ER specimens as the reference standard for the final diagnosis in a large consecutive series. METHODS: This was a cross-sectional retrospective study at a tertiary-referral center. A total of 354 consecutive patients with 397 GENs underwent ER (endoscopic mucosal resection or endoscopic submucosal dissection). Discrepancy rates between the histological results from EFB and ER specimens were assessed. Discrepancies that could affect patient outcome or clinical care were considered major. RESULTS: The overall histological discrepancy rate between EFB and ER specimens was 44.5% (95% confidence interval [CI], 39.7-49.5%) among the enrolled patients. The overall discrepancy rate was significantly higher in the intraepithelial neoplasia (IEN) group than in the carcinoma group (49.8% vs 25.6%, P < 0.001). The major discrepancy rate was also significantly higher in the IEN group than in the carcinoma group (36.6% vs 7.0%, P < 0.001). In subgroup analysis of the IEN group, a major histological discrepancy rate of 33.6% (70/208) for low-grade and 42.7% (44/103) for high-grade IEN was found, respectively. CONCLUSIONS: Endoscopic forceps biopsy was insufficient for a definitive diagnosis and therapeutic planning in patients with GEN. ER should be considered as not only definitive treatment but also a procedure for a precise histological diagnosis for lesions initially assessed as GEN by forceps biopsy specimens.

Clinicopathological correlation of PD-L1 and TET1 expression with tumor-infiltrating lymphocytes in non-small cell lung cancer.

The immunohistochemical analysis of PD-L1 expression is still important in cancer immunotherapy. PD-L1 expression is affected by various tumor microenvironmental factors including tumor infiltrating lymphocytes (TILs) and DNA methylation biomarkers. Given the complex communication between tumor cells and immune cells, we analyzed the expression of PD-L1 and TET1 with TILs in human NSCLC and the correlation with various clinicopathological characteristics and patient prognosis. A total of 96 cases of NSCLC were enrolled in this study. Using tissue microarray, we performed immunohistochemical staining to analyze PD-L1 and TET1 expression. Image-Pro Plus was used as an automated imaging analysis software program to analyze the density of CD3+, CD4+ and CD8 + TILs. PD-L1 expression was positively correlated with the density of CD3+, CD4+ and CD8 + TILs (p = 0.038, p = 0.020, and p = 0.009, respectively); however, no significant relationship existed between TET1 expression and any TILs. The survival analysis revealed that a high PD-L1 expression was associated with favorable prognosis for OS (p = 0.049) and DFS (p = 0.029) in advanced-stage II-IV patients, but not in early stage I. Density of CD8+ TILs was an independent and favorable prognostic factor for DFS (p = 0.008) and OS (p = 0.002) in early-stage I patients. However, high TET-1 expression was associated with poor prognosis for OS (p = 0.029) in total NSCLC patients. These findings suggest the correlation and favorable prognostic impact of PD-L1 and TILs in NSCLC. In addition, DNA demethylase TET1 has oncogenic effects, showing association with poor prognosis.

Ovarian yolk sac tumor with epithelial tumor component in a postmenopausal woman - case report and literature review.

Ovarian yolk sac tumors are common germ cell tumors usually arising in young women. Yolk sac tumors in elderly women are infrequently encountered and most of them are combined with other epithelial tumor components including endometrioid carcinoma or serous carcinoma. Here, we report an extremely rare case of a yolk sac tumor with mucinous tumor and large cell neuroendocrine carcinoma components in a postmenopausal woman, which is the third yolk sac tumor case with a neuroendocrine tumor element in an elderly woman. An 82-year-old female visited our hospital due to abdominal distention. Abdominal computed tomography (CT) demonstrated a solid and cystic mass, measuring about 9.0 cm in the largest diameter. A total hysterectomy with bilateral salpingo-oophorectomy and excisional biopsy of the peritoneal metastatic lesions was performed. Histologic evaluation revealed a malignant ovarian tumor composed of a variety of tumor components, including a yolk sac tumor, a mucinous tumor with multifocal mucinous carcinomatous areas, and a large-cell neuroendocrine carcinoma. After surgery, the patient refused further treatment and the disease recurred in the pelvic peritoneum and a left supraclavicular lymph node nine months later.

Vulvar epithelioid leiomyoma with myxoid change: A case report and literature review.

RATIONALE: Smooth muscle tumors of the vulva are infrequent neoplasms with diverse histologic features and unclear biologic behavior. Herein, we report a very rare case of vulvar epithelioid leiomyoma and review of previous reported cases of these tumors. In addition, we have discussed the representative diagnostic criteria of vulvar smooth muscle tumors and prognostic significance of epithelioid morphology. PATIENT CONCERNS: We recently met a 45-year-old woman with complaint of painful vulvar mass. INTERVENTIONS: Excisional biopsy was performed. DIAGNOSES: Pathologic examination revealed a vulvar epithelioid leiomyoma with multinodular growth pattern. Mitotic activity was rare and cellular atypia was not identified. Based on histology and immunohistochemical staining results, the case was diagnosed as vulvar epithelioid leiomyoma. OUTCOMES: After mass excision, the patient was discharged with no complication and there was no evidence recurrence for 6 months. LESSONS: After reviewing previous papers and diagnostic criterion, we thought that vulvar smooth muscle tumors with predominant epithelioid morphology may be associated with unfavorable prognosis, Therefore, pathologists should examine the epithelioid component in vulvar smooth muscle tumors carefully.

Composite trichoblastoma and inverted follicular keratosis: a case report.

Composite trichoblastoma and inverted follicular keratosis is extremely rare and the histogenesis is unclear. To date, only four cases have been described in a report. We report a case of 62-year-old woman patient with a palpable cutaneous nodule on the buttock. The patient had a history of squamous cell carcinoma on the lower lip 13 months ago. Excisional biopsy was done, and the microscopic examination revealed composite tumor of trichoblastoma and inverted follicular keratosis. The patient has not been experienced recurrence after surgery.

Bone regeneration strategy by different sized multichanneled biphasic calcium phosphate granules: In vivo evaluation in rabbit model.

A variety of synthetic materials are currently in use as bone substitutes, among them a new calcium phosphate-based multichannel, cylindrical, granular bone substitute that is showing satisfactory biocompatibility and osteoconductivity in clinical applications. These cylindrical granules differ in their mechanical and morphological characteristics such as size, diameter, surface area, pore size, and porosity. The aim of this study is to investigate whether the sizes of these synthetic granules and the resultant inter-granular spaces formed by their filling critical-sized bone defects affect new bone formation characteristics and to determine the best formulations from these individual types by combining the granules in different proportions to optimize the bone tissue regeneration. We evaluated two types of multichanneled cylindrical granules, 1 mm and 3 mm in diameter, combined the granules in two different proportions (wt%), and compared their different mechanical, morphological, and in vitro and in vivo biocompatibility characteristics. We assessed in vitro biocompatibility and cytotoxicity using MC3T3-E1 osteoblast-like cells using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and confocal imaging. In vivo investigation in a rabbit model indicated that all four samples formed significantly better bone than the control after four weeks and eight weeks of implantation. Micro-computed tomography analysis showed more bone formation by the 1 mm cylindrical granules with 160 ± 10 µm channeled pore and 50% porosity than the other three samples ( p<.05), which we confirmed by histological analysis.

Prognostic value of fibrosis ratio in metastatic lymph nodes of node-positive advanced gastric cancer.

Lymph node metastasis plays a crucial role in predicting prognosis in advanced gastric cancer (AGC). In the present study, we formulated a fibrosis ratio (FR), defined as the number of metastatic lymph nodes with fibrosis divided by the total number of lymph nodes, and sought to determine whether it can be used to predict the prognosis of patients with AGC and improve on existing node staging. We retrospectively analyzed 161 patients who underwent curative resection for node-positive AGC between 2001 and 2010, evaluating the association between FR, lymph node ratio (LNR), and micrometastasis, and the relationship between FR and clinicopathologic findings, overall survival (OS) and disease-free survival (DFS). A high FR was significantly related to T stage (P < .001), N stage (P < .001), tumor stage (P < .001), lymphatic invasion (P < .001), and venous invasion (P = .007). FR was significantly correlated with an increased number of metastatic lymph nodes (P = .001, R = 0.869) and LNR (P = .001, R = 0.943), but not with total harvested lymph nodes. Patients with micrometastases had a lower FR, compared with those without micrometastases (P < .001). A survival analysis showed poor OS for patients in the entire cohort (P < .001); N1 (P = .002), N2 (P = .004), N3a (P = .010), and N3b (P = .003) stages; and groups with high LNR (P = .013) and low LNR (P = .001). DFS was also poor for the entire cohort (P < .001) and the N2 (P = .013), N3b (P = .002), high-LNR (P = .036), and low-LNR (P = .001) groups, but not the N1 or N3a group. Univariate and multivariate analyses revealed that high FR was an independent prognostic factor for OS (hazard ratio [HR], 2.780; CI, 1.655-4.670; P < .001) and DFS (HR, 2.051; CI, 1.199-3.508; P = .009) in AGC. Collectively, our findings indicate that high FR is associated with adverse clinicopathologic parameters in AGC, clearly establishing nodal fibrosis as a pathological finding with value in predicting poor prognosis of patients with AGC. Thus, combining current N stage and LNR diagnostics with FR could improve prognostic prediction in AGC.