Benign Multicystic Peritoneal Mesothelioma: Two Rare Cases and Review of the Literature.

BACKGROUND: Benign multicystic peritoneal mesothelioma is a multiloculated cystic mass which originates from the peritoneum. This rare tumor is usually seen in women of childbearing age and has a high recurrence rate after surgery. CASE PRESENTATION: We present two benign multicystic peritoneal mesothelioma cases with different imaging modalities, which were also pathologically proven. CONCLUSION: The imaging features which may be diagnostic should be well known as there are very few reports regarding this entity.

Effects of thiostrepton alone or in combination with selumetinib on triple-negative breast cancer metastasis.

OBJECTIVE: FoxM1 transcription factor contributes to tumor metastasis and poor prognosis in many cancers including triple-negative breast cancer (TNBC). In this study, we examined the effects of FoxM1 inhibitor Thiostrepton (THIO) alone or in combination with MEK inhibitor Selumetinib (SEL) on metastatic parameters in vitro and in vivo. METHODS: Cell viability was determined by MTT assay. Immunoblotting and immunohistochemistry was used to assess metastasis-related protein expressions in 4T1 cells and its allograft tumor model in BALB/c mice. In vivo uPA activity was determined by enzymatic methods. RESULTS: Both inhibitors were effective on the expressions of FoxM1, ERK, p-ERK, Twist, E-cadherin, and Vimentin alone or in combination in vitro. THIO significantly decreased 4T1 cell migration and changed the cell morphology from mesenchymal-like to epithelial-like structure. THIO was more effective than in combination with SEL in terms of metastatic protein expressions in vivo. THIO alone significantly inhibited mean tumor growth, decreased lung metastasis rate and tumor foci, however, no significant changes in these parameters were observed in the combined group. Immunohistochemically, FoxM1 expression intensity was decreased with THIO and its combination with SEL in the tumors. CONCLUSIONS: This study suggests that inhibiting FoxM1 as a single target is more effective than combined treatment with MEK in theTNBC allograft model. The therapeutic efficacy of THIO should be investigated with further studies on appropriate drug delivery systems.

Tumor-Infiltrating Lymphocytes (TIL), Tertiary Lymphoid Structures (TLS), and Expression of PD-1, TIM-3, LAG-3 on TIL in Invasive and In Situ Ductal Breast Carcinomas and Their Relationship with Prognostic Factors.

INTRODUCTION: Immunotherapy has been determined as an important choice in breast carcinomas, especially in tumors with markedly inflammatory response. About this promising subject, tumor-infiltrating lymphocytes (TIL) and the expression of immune control point receptors on TIL have gained importance. MATERIALS AND METHODS: In this study, stromal TIL and tertiary lymphoid structures (TLS) were determined in tumor tissues of 312 invasive and 68 in situ breast cancer patients. Expression rates of PD-1, LAG-3, and TIM-3 on intratumoral and stromal TIL were immunohistochemically evaluated. RESULTS: In invasive breast carcinomas, stromal TIL was found to be significantly associated with lymph node metastasis, HR and HER2 expression, and basal-like phenotype, as the presence of TLS with neoadjuvant therapy, recurrence, death, and expression of HR and HER2. PD-1, LAG-3, and TIM-3 expressions were found to be associated with HR and HER2 status, stromal TIL rates, and TLS. In multivariate analysis, high stromal TIL and PD-1 expression in intratumoral TIL were found to be independent prognostic factors in terms of overall survival and disease-free survival. CONCLUSION: Evaluation of TIL and immune control point receptor expressions in breast cancer is particularly important in terms of planning the therapeutic approaches based on immunotherapy protocols.

Pancreatic metastasis of invasive ductal breast carcinoma: A potential diagnostic pitfall.

The 42-year-old patient, diagnosed with Stage IIA breast cancer, completed the postoperative adjuvant chemotherapy and radiotherapy. At the 11th year of diagnosis, a 3 cm tumor was detected in the pancreas and pancreatectomy was performed. Although the diagnosis of primary pancreatic adenocarcinoma was made at first, then the pancreatic metastasis of breast cancer was discovered. Pancreatic metastasis of breast cancer is extremely rare, and a limited number of patients have been reported in the literature. Here, we report an additional case of this rare tumor and the problems correlating with its diagnosis.

The Relationship Between Plexin C1 Overexpression and Survival in Hepatocellular Carcinoma: a Turkish Oncology Group (TOG) Study.

PURPOSE: Plexin C1 is a transmembrane receptor and plexin C1 overexpression might have role in carcinogenesis. Hepatocellular carcinoma (HCC) has poor prognosis because of its aggressive behavior and limited treatment options, especially in advanced stage. We recently documented that Plexin C1 was overexpressed in HCC. We aimed to evaluate the prognostic significance of Plexin C1 overexpression in HCC in the present study. METHODS: Plexin C1 overexpression was evaluated immunohistochemically on paraffin-embedded blocks of the HCC patients. Plexin C1 immunohistochemical staining was scored. Plexin C1 overexpression staining intensity and prevalence were used for plexin scale staining evaluation and plexin scores were estimated according this staining scale. Plexin C1 score and its association with survival and clinicopathological features was assessed. RESULTS: Sixty-seven HCC patients with adequate tissue for pathological evaluation were included. Median age was 63 years with male predominance (male to female ratio was 4.75 (n 57/12). Well-differentiated HCC (53.7%) patients had higher plexin C1 overexpression (p < 0.05). Median OS was 22.1 months. Patients with lower plexin C1 score (< 12) had shorter OS (17.5 vs 30.1 months, p = 0.036). Neutrophil count, GGT, and PNR (platelet/neutrophil ratio) had prognostic significance (p = 0.047, p = 0.018, and p = 0.045). CONCLUSION: Plexin C1 overexpression is inversely correlated with grade in HCC. The patients with lower rate of Plexin C1 overexpression have worse survival outcome. It might be a prognostic factor in HCC.

Diagnostic performance of 2D shear wave elastography in predicting liver fibrosis in patients with chronic hepatitis B and C: a histopathological correlation study.

PURPOSE: In this study, we investigated the diagnostic efficacy of 2D-Shear Wave Elastography (2D-SWE) in detecting stages of liver fibrosis and determining the disease-specific cut-off values in patients with chronic hepatitis B and C infection, using histopathological analysis as the reference method. METHOD: Our study included 103 consecutive adult patients with chronic hepatitis B and C infection (CHB and CHC) who had liver biopsy within three months of elastography examination. A real-time 2D-SWE was performed using the LOGIQ E9 system (GE Medical Systems, Wisconsin, USA). The correlation between the liver stiffness measurements and the METAVIR scores was evaluated. The diagnostic performance of 2D-SWE was assessed, and cut-off values were set. RESULTS: We found a statistically significant positive correlation between elastography values and the degree of liver fibrosis (Spearman's correlation coefficient = 0.76 and 0.83 for CHB and CHC; respectively) (p = 0.0001). The stiffness cut-off values were F ≥ 1: 5.92 kPa, F ≥ 2: 7.69 kPa, F ≥ 3: 8.97 kPa, F ≥ 4: 12.15 kPa in CHB; and F ≥ 1: 6.09 kPa, F ≥ 2: 7.81 kPa, F ≥ 3: 9.0 kPa, F ≥ 4: 12.47 kPa in CHC patients. CONCLUSION: 2D-SWE is reliable and accurate for the diagnosis of liver fibrosis. In selected patients, 2D-SWE may be useful in reducing the need for liver biopsy when staging fibrosis. Further studies in larger prospective series are needed to confirm these results and determine the most appropriate cut-off values for each stage of liver fibrosis.

Primary pulmonary angiosarcoma presenting as Pancoast tumor.

A primary pulmonary angiosarcoma is an extremely rare entity with fewer than 30 cases reported in the literature. We found no reports of primary pulmonary angiosarcoma presenting as a Pancoast tumor. We describe a case of pulmonary angiosarcoma located in the right superior sulcus that was treated by surgery.

The evaluation of the use of 2D shear-wave ultrasound elastography in differentiation of clinically insignificant and significant liver fibrosis in pediatric age group.

OBJECTIVE: To determine the accuracy of 2D shear-wave elastography (2D-SWE) in pediatric age group patients in differentiating clinically insignificant and significant liver fibrosis using METAVIR fibrosis scoring system as the gold standard. INTRODUCTION: Liver biopsy has long been the gold standard in liver fibrosis diagnosis. However, due to probable complications and sampling variabilities, the need for more accurate and non-invasive techniques has increased. 2D-SWE is a non-invasive technique used in the evaluation of liver stiffness and utilized more and more in routine clinical practice with recent advances and researches. MATERIALS AND METHODS: In this retrospective single-center study, we included 46 pediatric age group patients who had a liver parenchymal biopsy and 2D-SWE evaluation regardless of etiology. For 2D-SWE, the LOGIQ E9 system (GE Medical Systems, Wisconsin, USA) and, for histopathological evaluation, METAVIR fibrosis scoring system were utilized. Patients were further subgrouped as clinically insignificant (METAVIR Score F0-1) and significant (METAVIR Score F2-4). The Kolmogorov-Smirnov and Mann-Whitney U tests were employed for statistical analysis. The diagnostic accuracy of 2D-SWE was assessed, and cutoff values were set by ROC curve analysis. RESULTS: kPa values were statistically different between clinically significant and insignificant fibrosis patient groups (p < 0.001). kPa value of 8.92 was designated as the best cutoff value according to the Youden Index. CONCLUSION: 2D-SWE is one of the non-invasive techniques in the evaluation of liver fibrosis. Our findings suggest that 2D-SWE accurately differentiate clinically insignificant and significant liver fibrosis.

The Contribution of Additional Sampling in Cholecystectomy Materials: A Multicenter Prospective Study.

OBJECTIVE: Cholecystectomy materials are frequently encountered in routine practice. The aim of this study was to determine the true frequency of gallbladder lesions, the diagnostic consistency, and standardization of reports after macroscopic sampling and microscopic evaluation based on previously defined criteria. MATERIAL AND METHOD: 14 institutions participated in the study within the Hepato-Pancreato-Biliary Pathology Study Group. Routinely examined cholecystectomies within the last year were included in the study in these institutions. Additional sampling was performed according to the indications and criteria. The number of blocks and samples taken in the first macroscopic examination and the number of blocks and samples taken in the additional sampling were determined and the rate of diagnostic contribution of the additional examination was determined. RESULTS: A total of 5,244 cholecystectomy materials from 14 institutions were included in the study. Additional sampling was found to be necessary in 576 cases (10.98%) from all institutions. In the first macroscopic sampling, the mean of the numbers of samples was approximately 4 and the number of blocks was 2. The mean of the numbers of additional samples and blocks was approximately 8 and 4, respectively. The diagnosis was changed in 144 of the 576 new sampled cases while the remaining 432 stayed unaltered. CONCLUSION: In this study, it was observed that new sampling after the first microscopic examination of cholecystectomy materials contributed to the diagnosis. It was also shown that the necessity of having standard criteria for macroscopic and microscopic examination plays an important role in making the correct diagnosis.

Cucurbitacin B and cisplatin induce the cell death pathways in MB49 mouse bladder cancer model.

IMPACT STATEMENT: Alternative agents that will increase the effectiveness of cisplatin, which are widely used in the advanced stage and metastatic bladder cancer, are being investigated. In previous studies, Cucurbitacin B (CuB), which is a natural compound from the Cucurbitaceae family has been shown to inhibit the proliferation of tumor cells and create synergistic effects with cisplatin. In this study, we investigated the synergistic effect of CuB with cisplatin for the first time in bladder cancer in vitro and in vivo models. Our findings showed that CuB treatment with cisplatin reduced cell proliferation, and reduced tumor development through activating apoptosis and autophagy via PI3K/AKT/mTOR signaling pathway. Our results showed that CuB may be a new agent that can support conventional treatment in bladder cancer. Our study is important in terms of enlightening new pathways and developing new treatment methods in the treatment of bladder cancer.

Efficacy of a novel LyP-1-containing self-microemulsifying drug delivery system (SMEDDS) for active targeting to breast cancer.

An ideal cancer therapy targets the tumor cells selectively without damaging healthy tissues. Even though the tumor-specific markers are limited, these molecules can be used for the delivery of anti-cancer drugs as an active targeting strategy. Since the lymphatic system plays a critical role in the dissemination of cancer cells, the drugs directed through lymphatics can feasibly reach to the sites of metastasis. LyP-1 is a peptide that binds to the p32 receptor which is highly expressed not only on the lymphatic endothelium but also on the malignant cells; thus, making this peptide ligand a preferable candidate to mediate active targeting of lymphatics and cancer cells. In this study, different formulations of LyP-1 containing lipid-based nanopharmaceutics so-called self-microemulsifying drug delivery systems (SMEDDS) were developed and tested for their efficacy in targeting breast cancer. Following the selection of non-toxic formulation, doxorubicin hydrochloride and LyP-1 were co-administered in the SMEDDS, which resulted in a significant increase in in vitro cytotoxicity in p32-expressing breast cancer cells, 4T1 and MDA-MB-231. Accordingly, the uptake of LyP-1 in the SMEDDS by the cancer cells was demonstrated. The expression of p32 was detected in the 4T1 tumor tissues which were efficiently targeted with LyP-1 in the SMEDDS. When doxorubicin was co-administrated with LyP-1 in SMEDDS via intraperitonial administration, tumor growth and metastasis were significantly reduced. In conclusion, a novel and efficacious SMEDDS formulation containing LyP-1 with a droplet size less than 100 nm was developed for the lymphatic targeting of breast cancer.

Is it possible that the pathogenesis of osteoarthritis could start with subchondral trabecular bone loss like osteoporosis?

OBJECTIVES: This study aims to investigate the role of subchondral trabecular bone thickness in the mechanism of knee osteoarthritis and the correlation of osteoarthritis and osteoporosis pathogenesis. PATIENTS AND METHODS: The study included 62 patients (9 males, 53 females; mean age 66.7 years; range, 50 to 84 years) with osteoarthritis. All radiographs were evaluated according to Kellgren and Lawrence classification. The bone mineral density of the patients was measured and bone samples were collected from all patients included in the study during the surgical procedure and investigated pathologically. RESULTS: Osteoarthritis grade and trabecular bone thickness were correlated with each other. Trabecular thickness rate was higher in patients with severe osteoarthritis, whereas trabecular thickness rate was statistically significantly lower than the mean in patients with mild osteoarthritis (p=0.045). CONCLUSION: Trabecular thickness rate was significantly lower in the mild grade of osteoarthritis compared to the severe grade. As the level of osteoarthritis increased, the number of patients with osteoporosis decreased.

Evaluation of serum procollagen C-proteinase enhancer 1 level as a fibrosis marker in patients with chronic hepatitis B.

AIM: Although liver biopsy has long been considered the gold standard for staging fibrosis, because of the disadvantages and risks of biopsy, several noninvasive processes such as serum biomarkers have been introduced for the assessment of liver fibrosis. The aim of this study was to assess the diagnostic value of serum procollagen C-proteinase enhancer 1 (PCPE-1) as a noninvasive fibrosis marker in treatment-naive chronic hepatitis B patients. PATIENTS AND METHODS: This study included 126 patients with biopsy-proven hepatitis B and 50 healthy controls. Fibrosis stage was determined using the Ishak scoring system. The PCPE-1 level was measured using the enzyme-linked immunosorbent assay assay, and the aspartate aminotransferase to platelet ratio index and the FIB-4 index were calculated using the formulas described in Appendix 1 (Supplemental digital content 1, http://links.lww.com/EJGH/A277). RESULTS: Serum PCPE-1 levels of chronic hepatitis B patients were found to be significantly lower than those of the healthy control group (4.49±2.74 vs. 42.9±59.6 pg/ml, respectively, P<0.001). There was a statistically significant negative correlation between serum PCPE-1 level and fibrosis stage (P=0.011; r=-0.226). A statistically significant negative correlation was found between serum PCPE-1 level and necroinflammatory activity (P=0.030; r=-0.194). PCPE-1 levels of patients with liver fibrosis scores of F1-2 were statistically significantly lower than those of the healthy control group (P<0.001) (area under the receiver operating characteristic: 0.955). The area under the receiver operating characteristic of the PCPE-1 level was 0.615 for the prediction of fibrosis (F0 vs. F1-6) (P=0.039). CONCLUSION: Serum PCPE-1 might be used as a noninvasive marker of liver fibrosis. Further animal and human studies are needed to assess the utility of this marker.

Patient With Niemann-Pick Type C Presenting With a Jaw Mass Characterized With Lymph Node Involvement by Niemann-Pick Cells.

Niemann-Pick type C disease (NPC) is an autosomal recessive disorder resulting in accumulation of unesterified lysosomal cholesterol. An 8-year-old girl with NPC disease had a painless, rigid, and fixed mass measuring 3 cm in diameter located on the left angular region of mandibula. The mass biopsy showed lipid-laden phagocytic cells infiltrating the lymph node consistent with Niemann-Pick cells. In NPC, accumulation of cholesterol in tissues could be seen not only in reticuloendothelial and nervous systems, but also in all systems. Our case is important for it being the first case of NPC with submandibular lymphadenopathy characterized with NPC cell infiltration.

A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods: A Multicentre Study.

OBJECTIVE: As there is continuing disagreement among the observers on the differential diagnosis between the epithelial changes/lesions and neoplasms of the gallbladder, this multicentre study was planned in order to assess the rate of the epithelial gallbladder lesions in Turkey and to propose microscopy and macroscopy protocols. MATERIAL AND METHOD: With the participation of 22 institutions around Turkey that were included in the Hepato-Pancreato-Biliary Study Group, 89,324 cholecystectomy specimens sampled from 2003 to 2016 were retrospectively evaluated. The numbers of adenocarcinomas, dysplasias, intracholecystic neoplasms/adenomas, intestinal metaplasias and reactive atypia were identified with the review of pathology reports and the regional and countrywide incidence rates were presented in percentages. RESULTS: Epithelial changes/lesions were reported in 6% of cholecystectomy materials. Of these epithelial lesions, 7% were reported as adenocarcinoma, 0.9% as high-grade dysplasia, 4% as low-grade dysplasia, 7.8% as reactive/regenerative atypia, 1.7% as neoplastic polyp, and 15.6% as intestinal metaplasia. The remaining lesions (63%) primarily included non-neoplastic polypoids/hyperplastic lesions and antral/pyloric metaplasia. There were also differences between pathology laboratories. CONCLUSION: The major causes of the difference in reporting these epithelial changes/lesions and neoplasms include the differences related to the institute's oncological surgery frequency, sampling protocols, geographical dissimilarities, and differences in the diagnoses/interpretations of the pathologists. It seems that the diagnosis may change if new sections are taken from the specimen when any epithelial abnormality is seen during microscopic examination of the cholecystectomy materials.

Coexistence of idiopathic granulomatous mastitis and erythemanodosum: successful treatment with corticosteroids

Background/aim: Idiopathic granulomatous mastitis (IGM) is a rare, chronic inflammatory disease of the breast. Erythema nodosum (EN) is a rare extramammary manifestation of IGM. The purpose of this study is to determine the clinical and demographic characteristics of 11 IGM and EN patients and to evaluate the efficacy of methylprednisolone treatment. Materials and methods: In our series, ten patients had EN bilaterally, whereas one patient had a lesion of the right pretibial area. The mean age of the patients was 35.5 years (range: 29-45 years). IGM and EN were diagnosed by the necessary serological, microbiological, radiological, and histopathological examination. After diagnosis, methylprednisolone was started in the first week at 0.8 mg/kg daily for treatment. The weekly dose was tapered to 0.1 mg/kg daily over 8 weeks.Results: We started with the treatment of methylprednisolone, and in all our cases the initial response was excellent. In 2 weeks the IGM symptoms had markedly declined, while signs of EN disappeared completely. Patients were followed for an average of 60 months after treatment. None of the 11 patients had recurrence.Conclusion: We herein report a rare series considering IGM cases complicated by EN. Few such cases have been reported in the literature. We advocate for an initial trial of methylprednisolone treatment, which proved to be very successful in our patients.

The importance of serum biglycan levels as a fibrosis marker in patients with chronic hepatitis B.

BACKGROUND: Liver biopsy is recommended in the majority of patients with chronic viral hepatitis for fibrosis evaluation. Because of the potential risks of liver biopsy, many studies related to non-invasive biomarkers of hepatic fibrosis have been performed. We aimed to assess the diagnostic value of serum biglycan as a non-invasive fibrosis marker in chronic hepatitis B patients. METHODS: This study included 120 patients with biopsy-proven hepatitis B patients and 60 healthy controls. Fibrosis stage and necroinflammatory activity were assessed in liver biopsy specimens. Biglycan level was measured using an ELISA assay. RESULTS: Serum biglycan levels of chronic hepatitis B patients were found to be significantly higher than those of healthy controls (337.3±363.0 pg/mL vs 189.1±61.9 pg/mL, respectively, P<.001). There was a statistically significant positive correlation between serum biglycan level and fibrosis stage (P=.004; r=.213). Besides, a statistically significant positive correlation was found between serum biglycan level and necroinflammatory activity (P<.001; r=.271). The AUROC of BGN levels was 0.702 for fibrosis stage, differentiating patients from healthy controls with statistical significance (P<.001). The AUROC of BGN levels was 0.632 for necroinflammatory activity score, differentiating patients from healthy controls with statistical significance (P=.004). CONCLUSIONS: Serum biglycan might be used as a non-invasive marker of liver fibrosis. Further studies are needed to evaluate the usefulness of this marker.