Comparison between 18F-FDG PET/CT and diffusion-weighted imaging in detection of invasive ductal breast carcinoma.

Objectives: Breast carcinoma is the most common type of cancer in females. This study aims to compare fluorine-18-fluorodeoxyglucose (18F-FDG) uptake pattern and apparent diffusion coefficient (ADC) value for the detection of the primary tumour and axillary metastases of invasive ductal breast carcinoma. Methods: This study included 40 breast carcinoma lesions taken from 39 patients. After staging by positron emission tomography-computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (MRI), breast surgery with axillary lymph node dissection or sentinel lymph node biopsy was performed. Results: Primary lesion detection rate for PET/CT and diffusion-weighted MRI was high with 39 of 40 lesions (97.5%). The sensitivity and specificity for the detection of metastatic lymph nodes in axilla were 40.9%, 88.9%, with 18F-FDG PET/CT scans and 40.9%, 83.3%, for dw-MRI, respectively. No significant correlation was detected between ADC and SUVmax or SUVmax ratios. Estrogen receptor (p=0.007) and progesterone receptor (p=0.036) positive patients had lower ADC values. Tumour SUVmax was lower in T1 than T2 tumour size (p=0.027) and progesterone receptor-positive patients (p=0.029). Tumour/background SUVmax was lower in progesterone receptor-positive patients (p=0.004). Tumour/liver SUVmax was higher in grade III patients (p=0.035) and progesterone receptor negative status (p=0.043). Conclusions: This study confirmed the high detection rate of breast carcinoma in both modalities. They have same sensitivity for the detection of axillary lymph node metastases, whereas the PET/CT scan had higher specificity. Furthermore, ADC, SUVmax and SUVmax ratios showed some statistical significance among the patient groups according to different pathological parameters.

Pralatrexate for Peripheral T-Cell Lymphoma (PTCL): Chance Only Supports The Prepared Mind.

BACKGROUND: Due to their primary effects on DNA synthesis, antimetabolites are most effective against actively dividing cells and are significantly specific to the cell cycle phase. Pralatrexate (PDX), an antifolate metabolite designed to accumulate in cancer cells, was the first new agent approved by the US Food and Drug Administration for the treatment of resistant/recurrent peripheral T-cell lymphomas. PDX was a drug that is frequently used not only for PTCL, but also for cutaneous T-cell lymphoma (CTCL), extranodal natural killer (NK) / T-cell lymphoma. OBJECTIVE: This article reviews Pralatrexate's history, pharmacokinetics, clinical phase studies including phases I, II and III, types of cancers it is effective on, drug side effects, inhibition mechanism and even its use in the treatment of other cancers with innovative methods, including its antiviral effect against SARS-CoV-2 infection. METHODS: A comprehensive internet-based research was planned, covering all published and unpublished studies on the subject. We conducted this review in accordance with Preferred Reporting Items for systematic reviews and metaanalysis (PRISMA-P), and Cochrane Collaboration reporting items for systematic reviews and meta-analysis. The results of the studies in the articles were recorded to include all phase studies. RESULTS: Pralatrexate was structurally designed to have enhanced cellular transport via RFC (reduced folate carrier type) and be subject to more polyglutamation compared to methotrexate. The enhanced polyglutamylation ability of pralatrexate is associated with increased tumor cell death and ultimately improved anticancer activity. Pralatrexate is considered a promising drug for patients with recurrent and treatment-resistant PTCL with a good survival advantage. At the same time, it is an antifolate agent with a significant advantage over methotrexate as it does not cause myelosuppression. CONCLUSION: While there are manageable side effects such as thrombocytopenia, neutropenia, and mucositis, it is critical to explore new approaches, targeted agents, novel cellular therapies, and immunotherapies to determine optimal pretreatment in the rare but heterogeneous disease PTCL, and future studies and experienced haematologists are needed.

Unexpectedly High Coexistence Rate of In Situ/Invasive Carcinoma In Phyllodes Tumors. 10-Year Retrospective and Review Study.

Objective: Phyllodes tumors (PTs) are a rare group of breast tumors. Most malignant transformations are in situ carcinomas that are extremely rare and are limited to individual cases in the literature. The presence of in situ/invasive carcinomas is important as this may alter clinical judgment and management. In this study, we aimed to determine the association of in situ/invasive carcinomas among PTs. Materials and Methods: This retrospectively designed study included cases diagnosed with PTs between 2011 and 2020 in the pathology department of a tertiary level hospital. Tumors were grouped into benign, borderline and malignant, according to stromal overgrowth, stromal atypia, stromal cellularity and mitotic activity. In addition, age, location, type of operation, tumor diameter, and surgical margin information were recorded. in situ and/or invasive carcinoma foci accompanying the PTs were assessed. Results: A total of 29 patients diagnosed with PTs were identified, among whom 14 (48.2%) had benign PTs, 10 (34.4%) had borderline PTs, and 5 (17.2%) had malignant PTs. Of the patients with PTs, 3 (10.3%) had coexistent invasive carcinoma and 1 (3.4%) had carcinoma in situ. In this cohort the incidence of coexistence of PT and carcinoma was 4/29 (13.7%), which is much higher than previously reported (1.1% and 6%). The incidence of carcinoma was 2/5 (40%) in malignant PT patients and 2/10 (20%) in borderline PT patients. The coexistence of malignant PTs and carcinoma was significantly higher than those of benign and borderline PTs (p<0.05). Conclusion: The multidisciplinary team dealing with breast diseases has a great responsibility in both diagnosis and treatment. We anticipate that these rates will increase with an increase in the awareness and importance of this coexistence of carcinoma and PTs.

Comparison of urgent and elective thyroidectomy complications in Graves' disease.

BACKGROUND: Surgical treatment of Graves' disease (GD) has increased risk for bleeding, hypothyroidism and recurrent laryngeal nerve (RLN) palsy compared to other benign thyroidectomy indications. Nevertheless, it can be done safely in high volume centers. In some particular cases (i.e., anti-thyroid drug intolerance or thyrotoxicosis), urgent surgical treatment might be needed. In this study, we aimed to compare the complications of thyroidectomy in urgent and elective management of Graves' disease. METHODS: The patients, who underwent total thyroidectomy due to Graves' disease between 2012-2019 (n=113) were evaluated retrospectively in terms of demographics, pre-operative laboratory results, management, hospital admissions, operative and post-operative short-term outcomes, morbidity and mortality. Patients who were hospitalized to endocrinology department due to uncontrollable hyperthyroidism and related complications and who were prepared for surgery with Lugol's solution, plasmapheresis and steroids were considered as Urgent Group (n=12). Remaining 101 patients who underwent elective surgery considered as Elective Group. Surgical short-term outcomes, morbidity and mortality rates were compared. RESULTS: Of the 113 patients who were operated for GD, 92 were female and 21 were male. In urgently operated group, FT4 and FT3 levels were significantly higher (p<0.001 and p=0.001, respectively). There was no significant difference in transient or permanent hypocalcemia (p=0.821 and p=0.501, respectively), transient or permanent RLN palsy (p=0.356, p=0.634, respectively) and post-operative bleeding (p=0.338), between elective surgery and rapid optimization groups. CONCLUSION: Emergency surgery for Graves' disease can be performed safely with the application of effective pre-operative treatment protocols. KEY WORDS: Graves' Disease, Thyroidectomy complications, Urgent thyroidectomy.

Targeting the PANoptosome with 3,4-Methylenedioxy-ß-Nitrostyrene, Reduces PANoptosis and Protects the Kidney against Renal Ischemia-Reperfusion Injury.

OBJECTIVES: The objectives of this study were a) to investigate the effect of targeting the PANoptosome with 3,4-methylenedioxy-ß-nitrostyrene (MNS) on PANoptosis in the Renal ischemia-reperfussion (RIR) model b) to investigate the kidney protective effect of MNS toward RIR injury. METHODS: Thirty-two rats were divided into four groups randomly. The groups were assigned as Control, Sham, DMSO (dimethyl sulfoxide) and MNS groups. The rats in the MNS group were intraperitoneally given 20 mg/kg of MNS 30 minutes before reperfusion. 2% DMSO solvent that dissolves MNS were given to the rats in DMSO group. Left nephrectomy was performed on the rats under anesthesia at the 6th hour after reperfusion. Glutathione peroxidase (GPx), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and 8-Okso-2'-deoksiguanozin (8-OHdG) levels were measured. Immunohistochemical analysis, electron microscopic and histological examinations were carried out in the tissues. RESULTS: Total tubular injury score was lower in the MNS group (p < 0.001). Caspase-3, Gasdermin D and MLK (Mixed Lineage Kinase Domain Like Pseudokinase) expressions were considerably decreased in the MNS group (p < 0.001). Apoptotic index (AI) was found to be low in the MNS group (p < 0.001). CAT and SOD levels were higher in the MNS Group (p = 0.006, p = 0.0004, respectively). GPx, MDA, and 8-OH-dG levels were similar (p > 0.05) in all groups. MNS considerably improved the tissue structure, based on the electron microscopic analysis. CONCLUSIONS: Our results suggested that MNS administrated before the reperfusion reduces pyroptosis, apoptosis and necroptosis. These findings suggest that MNS significantly protects the kidney against RIR injury by reducing PANoptosis as a result of specific inhibition of Nod-like receptor pyrin domain-containing 3 (NLRP 3), one of the PANoptosome proteins.

Clinical adaptation of auxiliary methods and multidisciplinary approach to changing trends in parathyroid surgery.

ABSTRACT: To examine the effects of multidisciplinary approach and adjunct methods, on the surgical strategy, complications and treatment success of parathyroid surgery.Patients, who were operated for primary hyperparathyroidism (n = 411) at our institution between 2012 and 2019 were reviewed retrospectively. Preoperative imaging studies, surgical method, additional diagnostic methods used during surgery, frozen section results, and histopathology findings, complications, persistence, and recurrence were examined.Localization was determined by first-line examinations in 79.9% (n = 348). Four-dimensional computed tomography was used with an 83.3% success rate. Lateralization success for angiographic selective venous sampling was 80.3% and exact localization success was 65.1%. Bilateral neck exploration was performed in 10.6% (n = 37) of the patients, and in the remaining 89.4% (n = 311), minimally invasive parathyroidectomy (MIP) was performed. While the complication rate was higher in the bilateral neck exploration group (P = .019), persistence and recurrence rates were similar between 2 groups. During the study period, annual case volume increased from 9 cases to 103 cases (P < .001) and the rate of MIP increased from 44.4% to 92.8% over the years (P < .001).Effective use of adjunct techniques has increased the rates of MIP. The multidisciplinary approach has also provided low complication rates with the increasing number of cases.

Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study.

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR. Forty pathologists assessed sTILs as a percentage in digitalized biopsy slides, originating from 41 TNBC patients who were treated with NAC followed by surgery. Pathological response was quantified by the MD Anderson Residual Cancer Burden (RCB) score. Intraclass correlation coefficients (ICCs) were calculated per pathologist duo and Bland-Altman plots were constructed. The relation between sTILs and pCR or RCB class was investigated. The ICCs ranged from -0.376 to 0.947 (mean: 0.659), indicating substantial interobserver variability. Nevertheless, high sTILs scores were significantly associated with pCR for 36 participants (90%), and with RCB class for eight participants (20%). Post hoc sTILs cutoffs at 20% and 40% resulted in variable associations with pCR. The sTILs in TNBC with RCB-II and RCB-III were intermediate to those of RCB-0 and RCB-I, with lowest sTILs observed in RCB-I. However, the limited number of RCB-I cases precludes any definite conclusions due to lack of power, and this observation therefore requires further investigation. In conclusion, sTILs are a robust marker for pCR at the group level. However, if sTILs are to be used to guide the NAC scheme for individual patients, the observed interobserver variability might substantially affect the chance of obtaining a pCR. Future studies should determine the 'ideal' sTILs threshold, and attempt to fine-tune the patient selection for sTILs-based de-escalation of NAC regimens. At present, there is insufficient evidence for robust and reproducible sTILs-guided therapeutic decisions.

Comparison of two types of fixation for proximal tibial epiphysiodesis: An experimental study in a rabbit model.

OBJECTIVES: In this study, we describe a novel hemiepiphysiodesis technique to prevent implant-related perichondrial ring injury in a rabbit model. MATERIALS AND METHODS: Proximal tibial epiphyseal plates of a total of 16 white New Zealand rabbits were used for this animal model. The subjects were divided into three equal groups as follows: Group 1 (Kirschner wire [K-wire]/cerclage), Group 2 (8-plate) right-hind legs, Group 3 (Control) left hind legs. Using anteroposterior radiography, the medial slope angle (MSA), articular line-diaphyseal angle (ALDA), and the angle between screws of 8-plate in lateral X-ray tibial slope angle (TSA) were measured. The radiographs were taken early postoperative (Day 1) and on sacrification day (Week 8). The histological evaluation of the perichondrial ring was made on a 7-mm axial section that stained with Safranin O/fast green at X10 magnification. RESULTS: In both K-wire and 8-plate groups, the early postoperative ALDA and TSA were greater than the sacrification ALDA and TSA (p=0.028 and p<0.001, respectively). The early postoperative MSA was lower than the sacrification MSA in groups, (p<0.001). The MSA in the control group was lower than the K-wire and 8-plate groups (p<0.001 and p=0.009; respectively). The perichondrial ring thickness of the K-wire group was greater than the 8-plate group in histological evaluation (p<0.001). CONCLUSION: Both of the K-wire and 8-plate groups showed similar angulation effects in the proximal tibia, although histologically less damage to the perichondrial ring was observed in the K-wire group, compared to the 8-plate group.

A novel coenzyme-Q approach for the prevention of postsurgical adhesion.

OBJECTIVES: Postoperative intraperitoneal adhesions are an unsolved and important problem in abdominal surgery. In the present study, the probable preventive role of coenzyme-Q in the development of peritoneal adhesions was investigated. MATERIAL AND METHODS: Sixteen Wistar Hannover male rats weighing 300-350 g were randomly separated into two groups of 8 rats each. The cecum was abraded with a sterile gauze until sub-serosal hemorrhage developed. A patch of peritoneum located opposite to the cecal abrasion was completely dissected. No treatment was given to Group 1. Group 2 received 30 mg/kg coenzyme-Q, which was injected 2 mL intraperitoneally. All the rats were sacrificed on the postoperative 21st day, and after adhesions were scored macroscopically, tissue specimens of the peritoneum and bowel were subjected to histopathological investigation. Tissue and blood specimens were also taken for biochemical analysis to investigate antioxidant efficiency. RESULTS: Adhesion scores were significantly different between the control group and the coenzyme-Q group (p= 0.001). According to the tissue levels of GSH-Px, MDA, and SOD levels, there was no significant difference between the study groups (p= 0.074, p= 0.208, p= 0.526). According to the plasma GSH-Px and SOD levels, there was significant difference between the groups (p= 0.002, p= 0.001), but the difference was not significant at MDA levels (p= 0.793). The differences between the pathological scores of the control and coenzyme-Q (p= 0.028 for fibrosis; p= 0.025 for inflammation) groups were statistically significant. CONCLUSION: This study confirms that coenzyme-Q is the potential application in the prevention of early postoperative adhesions.

The Controversy of Surgical Intervention for Anal Canal Duplication in Children.

OBJECTIVE: Since the first definition of anal canal little has been discovered about the etiology of this rare condition. We present four asymptomatic cases of anal canal duplication with diverse clinical and surgical findings. METHODS: A retrospective chart review was performed on four infants presenting with asymptomatic anal canal duplication, born between 2014 and 2016. Clinical characteristics and pathologic findings of patients either by radiological imaging or pathology were evaluated. The primary outcome measure was the complications. RESULTS: All patients were followed-up with physical examination and ultrasound for a mean of 3.5±1.0 years, lastly seen at the beginning of 2018. The female to male ratio was 3:1. Duplicate anal canal length varied between 12-20mm, and two of the four patients had a presacral cystic mass confirmed as a tail gut cyst following surgery. At follow-up, none of the patients had developed symptoms related to anal canal duplication, regardless of whether they had surgical intervention. CONCLUSION: Though surgical management is the preferred treatment for anal canal duplication, it seems that patients who do not undergo surgery might remain free of symptoms, suggesting that surgical intervention may be unnecessary.

Effect of tadalafil on penile nitric oxide synthase and corporal smooth muscle in rats under dutasteride treatment.

Aim: To investigate the effect of tadalafil in rats administered with daily dutasteride.Methods: Twenty-four Sprague-Dawley male rats were allocated to three groups as control (group C), dutasteride (group D) and dutasteride plus tadalafil (group D + T). After a month of treatment, serum samples were obtained from rats to measure dihydrotestosterone and total testosterone. Nitric oxide (NO) synthase (NOS) immunoreactivity and levels of NOS enzyme isoforms, NO and cyclic guanosine monophosphate (cGMP) were evaluated in the harvested penile tissues. Also, corporal smooth muscle and collagen were examined.Results: Staining intensities of neuronal NOS and endothelial NOS were significantly lower in group D (p < .05). They were similar between group C and group D + T. Immunoreactivity of inducible NOS was observed higher in group D than group C (p = .01) whereas group D + T had the highest iNOS (p<.001). ELISA revealed similar outcomes in terms of NOS enzyme isoform levels. The mean of smooth muscle to collagen ratio was the lowest in group D (p < .001) and it was similar among group C and group D + T (p = .072). Group D had the lowest cGMP and NO levels (p < .05) and they did not differ between group C and group D + T (p>.05). Group D and group D + T had significantly decreased dihydrotestosterone and increased testosterone, compared to group C (p < .001). They were similar between group D and group D + T.Conclusion: Daily treatment with tadalafil improves dutasteride-induced changes in rat penis.

Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study.

Histopathological assessment of ductal carcinoma in situ, a nonobligate precursor of invasive breast cancer, is characterized by considerable interobserver variability. Previously, post hoc dichotomization of multicategorical variables was used to determine the "ideal" cutoffs for dichotomous assessment. The present international multicenter study evaluated interobserver variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive ductal carcinomas in situ. All pathologists independently assessed nuclear atypia, necrosis, solid ductal carcinoma in situ architecture, calcifications, stromal architecture, and lobular cancerization in one digital slide per lesion. Stromal inflammation was assessed semiquantitatively. Tumor-infiltrating lymphocytes were quantified as percentages and dichotomously assessed with a cutoff at 50%. Krippendorff's alpha (KA), Cohen's kappa and intraclass correlation coefficient were calculated for the appropriate variables. Lobular cancerization (KA = 0.396), nuclear atypia (KA = 0.422), and stromal architecture (KA = 0.450) showed the highest interobserver variability. Stromal inflammation (KA = 0.564), dichotomously assessed tumor-infiltrating lymphocytes (KA = 0.520), and comedonecrosis (KA = 0.539) showed slightly lower interobserver disagreement. Solid ductal carcinoma in situ architecture (KA = 0.602) and calcifications (KA = 0.676) presented with the lowest interobserver variability. Semiquantitative assessment of stromal inflammation resulted in a slightly higher interobserver concordance than upfront dichotomous tumor-infiltrating lymphocytes assessment (KA = 0.564 versus KA = 0.520). High stromal inflammation corresponded best with dichotomously assessed tumor-infiltrating lymphocytes when the cutoff was set at 10% (kappa = 0.881). Nevertheless, a post hoc tumor-infiltrating lymphocytes cutoff set at 20% resulted in the highest interobserver agreement (KA = 0.669). Despite upfront dichotomous evaluation, the interobserver variability remains considerable and is at most acceptable, although it varies among the different histopathological features. Future studies should investigate its impact on ductal carcinoma in situ prognostication. Forthcoming machine learning algorithms may be useful to tackle this substantial diagnostic challenge.

PTEN loss is a predictive marker for HER2-positive metastatic breast cancer patients treated with trastuzumab-based therapies.

PURPOSE: The purpose of this study was to retrospectively investigate the response to trastuzumab in breast cancer patients in terms of the potential roles of several oncogenic pathways (phosphatase and tensin homolog (PTEN) and phosphatidylinositol 3-kinase (PI3K)) in relation to HER2 status. METHODS: Paraffin-embedded primary tumor tissues of 100 HER2 positive metastatic breast cancer patients who received trastuzumab were analyzed with immunohistochemistry for p85 (PI3K) and PTEN. The relationship between variables was tested via chi-square, Fischer's exact test and Mann-Whitney U test, where appropriate. Progression-free survival (PFS) and overall survival (OS) were calculated with the Kaplan-Meier method and survival curves of subgroups were compared with the log-rank test. Results: The level of immunohistochemical expression of PI3K was 42%. Loss of PTEN was observed in 43% of the patients. PTEN-expressing tumors had statistically higher response rates for trastuzumab than tumors not-expressing PTEN (p=0.012). PI3K expression had no significant effect on trastuzumab response. Median PFS for PTEN-expressing and not-expressing tumors were 15.3 months (95% CI, 12.6-34) and 12.1 months (95% CI, 7.9-16.2), respectively (p=0.04). The level of PI3K expression had no effect on PFS and OS in our patient population. CONCLUSIONS: Loss of PTEN predicted poorer response to trastuzumab treatment and shorter PFS but not OS. We could not find an effect of PI3K expression on the above-mentioned parameters.

Therapeutic effectiveness of rectally administered fish oil and mesalazine in trinitrobenzenesulfonic acid-induced colitis.

AIM: Fish oil (FO) and mesalazine have well-known anti-inflammatory and antioxidant effects; on the other hand, information related to combined intrarectal administration of FO and mesalazine is limited. The present study was conducted to make comparison on therapeutic effectiveness of rectally administered FO and mesalazine in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis. METHODS: Wistar rats were randomly assigned to 5 groups as (1) Control, (2) Colitis, (3) Colitis + Mesalazine (Colitis + M), (4) Colitis + Fish Oil (Colitis + F), and (5) Colitis + Mesalazine + Fish Oil (Colitis + M + F). Intrarectally administered TNBS induced colitis. At the end of the trial, the rats' macroscopic and histopathologic lesions were rated and tumour necrosis factor (TNF)-α, Interleukin 6 (IL6), glutathione reductase (GR), glutathione peroxidase (GP), myeloperoxidase (MPO), malondialdehyde (MDA), Superoxide dismutase (SOD), Total nitrate and nitrite, and catalase (CAT) in serum and tissue were detected. RESULTS: As a result of macroscopic and microscopic examination, although separate administrations of FO and mesalazine partly decreased the damage, their combined administration decreased the damage scores significantly (p < 0.01). It was observed that separate and combined administrations of FO and mesalazine decreased the increase in the serum and tissue TNF-α and IL-6 levels caused by colitis (p < 0.05). It was observed that the serum MPO, serum GR, tissue SOD, tissue nitrite/nitrate values of both Colitis + M and Colitis + F groups were close to the control in terms of all the parameter values in Colitis + M + F group (p > 0.05). Also based on the histological results, the inflammation damage in the tissue caused by colitis in the Colitis + M + F group recovered significantly. CONCLUSIONS: We found that microscopic and macroscopic damage, serum IL-6 level decreased and increased serum and tissue GP and tissue GR values in Colitis + M + F group compared to Colitis + M and Colitis + F groups. Combined intrarectal administration of FO and mesalazine may bring a new insight concerning the treatment of ulcerative colitis.

Spread through air spaces (STAS) is a predictor of poor outcome in atypical carcinoids of the lung.

Spread through air spaces (STAS) have been recently recognized as a prognostic factor for adenocarcinoma and squamous cell carcinoma of the lung. Pulmonary neuroendocrine neoplasms (NENs) include tumors with different morphology and a heterogeneous clinical behavior. Among atypical carcinoids (ACs), new prognostic factors able to refine prognosis are needed. In the present study, a retrospective series of 91 surgically resected ACs was investigated, in parallel with 191 control cases of typical carcinoids (TCs) and of high-grade small- and large-cell neuroendocrine carcinomas, to assess the presence and potential prognostic role of STAS. STAS was defined by the presence of neoplastic nests or single cells in air spaces beyond the tumor edge. Clinicopathological parameters and survival were correlated by univariate and multivariate analyses. STAS was identified in 48% of ACs (44/91) compared to 20.5% of TCs and 71-88% of high-grade large- and small-cell carcinomas in the control group. In the carcinoid group, presence of STAS was significantly correlated with unfavorable parameters, such as high tumor stage, positive nodal status, high Ki-67 index, presence of angioinvasion, and with adverse disease outcome, shorter overall survival, and time to progression. In conclusion, the presence of STAS is an additional relevant adverse prognostic factor in pulmonary AC that currently has the most unpredictable outcome and the most controversial treatment strategy.

Protective and therapeutic effects of milrinone on acoustic trauma in rat cochlea.

OBJECTIVE: The aim of this study was to investigate the potential protective and therapeutic effects of milrinone, a specific phosphodiesterase (PDE) III inhibitor, on acoustic trauma-induced cochlear injury and apoptosis. METHODS: A total number of 30 healthy Wistar albino rats were evenly divided into five groups as follows: group 1 was assigned as control group; group 2 and 3 were assigned as low-dosage groups (0.25 mg/kg) in which milrinone was administered 1 h before acoustic trauma (AT) and 2 h after AT, respectively; group 4 and 5 were assigned as high-dosage groups (0.50 mg/kg) in which the drug was administered 1 h before AT and 2 h after AT, respectively. Except control group, all treatment groups received a single dosage of milrinone for 5 days. Distortion product otoacoustic emissions (DPOAE) measurements were recorded before AT as well as at second and fifth post-traumatic days. At the end of fifth day, all rats were sacrificed and the cochlea of the rats was removed for histopathological evaluation. In addition, the groups were compared in terms of apoptotic index via caspase-3 staining. RESULTS: In terms of signal-to-noise ratio (SNR), there was no statistically significant difference among the groups following AT (p > 0.05). After 5 days of milrinone treatment, the best SNR values were found in group 5, though all groups did not statistically differ (p > 0.05). In histopathological evaluation, vacuolization, inflammation, and edema scores in all treatment groups were statistically lower than those of the control group (p < 0.05). In group 2 and 4 where the drug was administered before AT, the inflammation and apoptosis index was lower than those of group 3 and 5 where the drug was administered after AT (p < 0.0001). CONCLUSION: We reveal that milrinone has a protective effect on cochlear damage in the experimental acoustic model of rats. This protective effect was more apparent following the pre-traumatic milrinone administration, and is associated with its effect on decreasing inflammation and apoptosis. Based on DPOAE measurements following AT, especially in the group 5 (high-dosage group), milrinone may also have a therapeutic effect.

Tadalafil Preserves Penile Nitric Oxide Synthase from Detrimental Effect of Paroxetine in Rats.

OBJECTIVE: Paroxetine is a commonly prescribed SSRI that can impair erectile function in animal models via inhibition of nitric oxide synthase (NOS). Tadalafil potentiates nitric oxide (NO)-mediated responses in isolated trabecular smooth muscle and penile erection. The purpose of this study was to evaluate the impact of co-administering tadalafil with paroxetine on penile NOS levels in rats. MATERIALS AND METHODS: A total of 30 male Sprague-Dawley rats were divided into 3 groups as control (Group-C), paroxetine (Group-P) and paroxetine plus tadalafil (Group-P+T). After 28 days of treatment, rats were sacrificed and their penile tissues were harvested for analysis. NOS isoform protein levels and immunoreactivity scores of NOS were assessed. Statistical significance level was set at p<0.05. RESULTS: Neuronal NOS (nNOS) levels were significantly decreased in group-P, compared with group-C (p<0.001). In comparison, rats in group-P+T had significantly higher nNOS levels compared to group-P (p<0.001). Endothelial NOS (eNOS) and inducible NOS (iNOS) levels were significantly higher in group-P compared with group-C (p<0.01). The levels of eNOS and iNOS in group-P+T were similar to group-C. CONCLUSION: Daily treatment with tadalafil prevented chronic paroxetine-induced changes in all three NOS isoform levels. Tadalafil treatment may therefore be a useful therapy in men with paroxetine-associated erectile dysfunction.

Is Ozone (O3) Treatment Effective in Atrophic Rhinitis? Experimental Animal Study.

INTRODUCTION: Atrophic rhinitis (AR) is a disease characterized by atrophy of the mucosa, submucosa, bone tissue due to an unknown cause and excessive nasal cavity enlargement. The disease still has no complete treatment, and the treatment of the functional loss of atrophic cells in AR is still a matter to be investigated. Ozone (O3) therapy has been shown to enhance cell metabolism, angiogenesis, fibroblast activity, and collagen synthesis. AIM: To determine whether ozone treatment affects the disease histopathologically, in experimentally created AR. Material - Method: Twelve Wistar Hanover strain albino male rats were included in the study. Atrophic rhinitis was induced in animals by administering Pasteurella multocida toxin diluted with saline for 21 days to both nasal cavities. A total of 12 animals included in the study were divided into 2 groups as control and study. Ozone gas (60 µg/mL) was administered rectally to the study group for 21 days. After 2 weeks, the rats were decapitated, the nasal cavities were removed as a block, and atrophic rhinitis parameters (epithelial hyperplasia, goblet cell loss, cilia loss, inflammatory infiltration, and vascular ectasia) were evaluated under light microscopy by histopathological examination and statistically interpreted. RESULT: The incidence of vascular ectasia was significantly lower in the ozone group compared to the control group (p<0.05). There was no significant difference between the groups regarding other histopathologic findings. CONCLUSION: Ozone treatment was moderate at the histopathological level. We concluded that ozone therapy has no or very limited effect on atrophic rhinitis.

Long-term outcomes in pediatric appendiceal carcinoids: Turkey experience.

The tendency of non-operative management of appendicitis let us explore the natural history of appendiceal carcinoids, compare them with appendicitis patients, and determine the possibility of deciding the extent of the surgery and post-operative follow-up on behalf of the intraoperative findings. A retrospective review was performed of patients with appendicitis between 2009 and 2017. Of 2781 patients, 10 (0.36%) were diagnosed with appendiceal carcinoids. Sixty percent were female with an average age of 13.10 ± 1.73. The mean tumor size was 0.97 ± 0.34 cm with 70% located at the tip. Majority had an insular pattern (n = 9), six had subserosal fat tissue invasion, one had extension to mesoappendix, one had vascular invasion, and two had lymphatic invasion. The average mitotic index was 3.20 ± 1.40/50HPF, and Ki 67 activity was 3 ± 1.7%. The mean follow-up period was 66.40 ± 25.92 months. Patients were further evaluated with ultrasonography (n = 10), CT (n = 3), and MRI (n = 10). Serum markers including chromogranin (n = 9), NSE (n = 6), and 5-HIAA (n = 6) were normal. None required further treatment and had any symptoms of carcinoid syndromes or recurrences post-operatively.Conclusion: Other than appendectomy, no additional surgery or follow-up is required in appendiceal carcinoids less than 1.5 cm in size, regardless of the lymphoid or vascular invasion. What is Known: • The treatment of patients with a 1-2-cm tumor is not clear in both the pediatric and adult populations, and additional resection is needed. • Patients are monitored post-operatively with radiological and/or biochemical testing. What is New: • Appendectomy is curative for tumors less than 2 cm. • No additional surgery or follow-up is required in appendiceal carcinoids less than 1.5 cm in size regardless of the lymphoid or vascular invasion.

Blaschko-linear "Congenital Mixed Hemato-lymphangio-keratoma Serpiginosum" Naeviforme: A New Hybrid Entity or Various Morphological Reflections of the Two Different Vascular Abnormalities?

We present the case of a 15-year-old girl who presented with an unusual grouping of lesions on her upper left leg. The lesions had been present since birth. The patient had five different types of lesions: 1) transparent grouped or scattered yellowish vesicles; 2) keratotic-surfaced, grouped dark-yellowish papules; 3) bright-red grouped papules; 4) keratotic-surfaced grouped dark-red papules; and 5) patchy, punctate, and erythematous red macules. All of the lesions were intertwined along the lines of Blaschko and were in the form of irregular serpiginous plaques. Histopathological examinations of the lesions showed three main histological features, and diagnoses of the lesions were made as lymphangioma circumscriptum, lymphangiokeratoma, and verrucous hemangioma. To the best of our knowledge, such intertwined lesions have never been reported in the literature. Hence, we suggest that the name of this unique combination of lesions be "congenital nevoid mixed hemato-lymphangio-keratoma serpiginosum."