[Potential therapeutic implication of focal adhesion kinase in small-cell lung cancer]. / Implication thérapeutique potentielle de la kinase de l'adhérence focale dans le cancer pulmonaire à petites cellules.

The molecular steps leading to small cell lung cancer (SCLC) development and progression are still poorly understood, resulting in the absence of targeted therapy and an extremely poor prognosis. Activation of Focal Adhesion Kinase (FAK) plays a key role in the invasive behavior of this cancer in vitro. Our hypothesis is that FAK could be a therapeutic target in SCLC. Our work aims to describe a mouse model to study the role of FAK and the antitumoral potential of its inhibition in SCLC in vivo.

A comparison of hernia sac ligation versus invagination in Lichtenstein tension-free mesh hernioplasty: does the type of hernia play a role in outcomes?

BACKGROUND: Management of the indirect hernial sac in inguinal hernia repairs has long been a subject of debate among general surgeons. Although hernial sac high ligation (HL) is a time-honored concept in groin hernia surgery, non-ligation/invagination is gaining popularity. This study was intended to compare the effects of hernia sac ligation and invagination in patients undergoing Lichtenstein mesh hernioplasty (LMH). Another aim was to investigate the possible association between the hernial defect size and postoperative early pain in both groups. METHODS: Patients with indirect inguinal hernia undergoing elective LMH under spinal anesthesia were included in this prospective randomized study. Patients were classified according to European Hernia Society (EHS) criteria and were randomized into two groups, HL and non-HL/invagination. Postoperative pain levels at 6, 12, and 24 h, 7 days, and 1 year were compared using a ten-point visual analog scale (VAS). In addition, recurrence was examined in the postoperative first year. Postoperative complications, length of hospital stay, drain use, and surgery times were evaluated as secondary outcomes. This study was registered at www. CLINICALTRIALS: gov . (The clinicaltrials.gov ID number is: NCT05308251). RESULTS: Ninety-three out of a total of 108 patients were included in the study between January 2020 and January 2021 (HL group n = 44, non-HL group n = 49). Demographic characteristics were comparable between the groups. Mean VAS scores were significantly higher in the HL group at 6 and 12 h postoperatively (p < 0.05 and p = 0.036 respectively). While there was no difference in pain levels between the groups in EHS 1 and EHS 2 hernias (p > 0.05 for all), VAS scores were significantly higher in the ligation group in EHS 3 hernias (p < 0.05 for all). Recurrence and complication rates were unaffected with non-ligation at a median 18 months follow-up. CONCLUSION: Hernia sac invagination was superior to ligation in patients who underwent LMH, as it reduced early postoperative pain levels without disturbing repair integrity. We therefore recommend that ligating the hernial sac be avoided, especially in EHS 3 patients who undergo LMH.

Illustration of a fatal radiation-induced lung aneurysm: Is central lung stereotactic radiotherapy to be banned?

Stereotactic body radiation therapy is still controversial for inoperable patients with central lung lesion. We report the case of a 59-year-old woman with previous history of head and neck squamous cell carcinoma who was treated by lung stereotactic body irradiation for an inoperable lymph node in station 10R. One year after, a fibroscopy showed a necrosis of the right main bronchus mucosae and the CT showed a radio-induced aneurysm protruding into the right inferior lobular bronchus. The patient eventually died a few hours later with a massive haemoptysis. This case highlights the potential toxicity of central lung stereotactic body radiation therapy and raises the question of its legitimacy.

Comparison of the effect of ranibizumab and dexamethasone implant in diabetic macular edema with concurrent epiretinal membrane.

OBJECTIVE: To compare the efficacy and safety of intravitreal ranibizumab (RZB) injections and intravitreal dexamethasone (DEX) implant in diabetic macular edema (DME) with concurrent epiretinal membrane (ERM). METHODS: This was a retrospective, observational, comparative study. Medical records of DME patients with concurrent ERM were retrospectively reviewed. Seventeen eyes of 16 patients treated with 3 consecutive monthly RZB injections (RZB group) and 22 eyes of 18 patients treated with a DEX implant (DEX group) were included. The groups were compared at baseline, 1st, 2nd, 3rd and 4th months in terms of best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP). RESULTS: Eighteen of the 39 eyes (46.1%) were phakic at baseline, 9 (52.9%) of which were treated with RZB, whereas 9 (40.9%) were treated with DEX implant (P=0.528). Although CMT improved significantly in both the RZB and DEX groups (P<0.001); the trend was different (P=0.003). The mean change in CMT at 1month in the DEX group was greater (DEX: 188.2±142.7µm; RZB: 95.7±110.7µm; P=0.034); it was in favor of RZB group at the 3rd and 4th months (DEX: -52.7±86.9µm; RZB: 1.4±31.4µm; P=0.012. DEX: -63±67.3µm; RZB: -5.8±43.9µm; P=0.004, respectively). BCVA improved significantly in both groups (P<0.001). There was no statistical difference between the groups with regard to gain in BCVA or IOP change throughout the study period (P=0.572, P=0.064, respectively). CONCLUSION: Both RZB and DEX are effective in improving anatomical and visual outcomes in DME with concurrent ERM. The DEX group was associated with a prompt anatomic response, but with a gradual decrease from 3rd month.

Comparison of East and West Survival Nomograms in Turkish Gastric Cancer Patients Who Underwent Radical Surgery.

BACKGROUND AND AIM:: The clinicopathological demonstrations of gastric cancer vary widely between Eastern and Western countries. Turkey is situated in Europe and Middle East which acts as a bridge between east and west. We aimed to validate the two popular nomograms of east and west origin by means of patients who underwent curative surgery for gastric cancer in our country. MATERIAL AND METHODS:: Of the 202 patients diagnosed with gastric cancer between the years 2006 and 2013, 145 of these patients whose data were sufficient were included in the study. For all patients, demographic, laboratory, operative, and pathologic findings were documented. For each patient, prognostic factors were incorporated into the nomograms for estimating 5-year survival probability. RESULTS:: For a Turkish cohort, the western nomogram showed a better discriminative capacity (AUC = 0.721, 95% confidence interval 0.637-0.806) and was better calibrated (the Hosmer-Lemeshow goodness-of-fit test p = 0.323), as compared to the eastern nomogram with AUC = 0.615, 95% confidence interval 0.522-0.708, and p = 0.077, respectively. CONCLUSION:: Western nomogram was found to be more effective than eastern nomogram in prediction of estimating 5-year survival probability in patients with resectable gastric cancer in Turkish population.

Effectiveness of crizotinib in a patient with ALK IHC-positive/FISH-negative metastatic lung adenocarcinoma.

We report a case of crizotinib effectiveness in a heavily pretreated patient with a metastatic NSCLC initially considered IHC-positive and FISH-negative for ALK rearrangement. After repeated analyses of tumor samples, borderline ALK FISH-positivity (18.5% positive cells) was demonstrated.

Anesthesia for adult rigid bronchoscopy.

Rigid bronchoscopy under general anesthesia enables performing diagnostic and/or therapeutic procedures in the tracheobronchial tree. This technique is characterized by specific technical problems, insofar as the anesthesiologist and the operators share the same space, namely the airway. Several potential complications (hemorrhage inside the airway, threat to ventilation ...) may arise. These challenges render the ability to use the variable available techniques essential, as well as knowledge of the complications they could entail, and the ability to rapidly solve them. General anesthesia is usually total intravenous anesthesia, using short acting agents. Ventilation can be spontaneous, but more often insured using high-frequency jet ventilation. The hospital infrastructure and staff must have the expertise to perform this particular procedure, in order to limit the complication rate.

Thyroid cancer in hyperthyroid patients: is it different clinical entity?

OBJECTIVE: In this retrospective study, we aimed to analyze the frequency of thyroid cancer in patients who underwent thyroidectomy for hyperthyroidism. PATIENTS AND METHODS: A total number of 177 patients, who underwent surgery for hyperthyroidism between August 2005 and March 2010, were included in this study. Demographic, clinical, radiologic, and laboratory data were collected retrospectively.Results. Postoperative histopathological examinations revealed thyroid malignancy in 13 (7.3%) patients. Among these 13 patients presenting thyroid malignancy, 53.9% were diagnosed with multinodular toxic goiter (MTG), 38.5% with uninodular toxic goiter (UTG) and 7.6% with Graves' disease. CONCLUSIONS: Thyroid carcinoma is common in hyperthyroidism and thyroid fine-needle aspiration biopsy (TFNAB) is a reliable method in the diagnosis of the thyroid malignancy in these patients. We suggest that it is reasonable to evaluate nodules with TFNAB in hyperthyroid patients prior to surgical intervention.

Combined endoscopic ultrasonography and endobronchial ultrasound-fine-needle aspiration for evaluation of mediastinal lymph nodes.

OBJECTIVES: Endoscopic ultrasonography (EUS) and endobronchial ultrasound-fine-needle aspiration (EBUS-FNA), is an accurate technique for evaluation of mediastinal lymph nodes (MLN) and stadification of lung cancer. The aims of the study are to evaluate the feasibility and the efficacy of the combined technique compared with mediastinoscopy for the diagnosis of MLN. DESIGN AND METHODS: All patients with suspected malignant MLN and/or lung lesion identified by positron emission tomography-computed tomography underwent combined EUS-EBUS-FNA. The combined procedure was performed in outpatients under general anesthesia for EUS and sedation by intravenous midazolam for EBUS when performed separately, using linear-array echoendoscopes. The MLN were punctured during the EUS and EBUS-FNA procedures with a 22 gauge needle. RESULTS: Thirty-four patients underwent consecutively EUS and EBUS-FNA between September 2011 and November 2013 (8 women, 26 men, mean age of 65.9 year, range: 51-83). Combined EUS-EBUS-FNA was performed in a single time procedure in 26 patients (mean time 50 min) and in two different times in eight patients (mean delay 3 days). Twenty-five malignant and 9 inflammatory lesions were diagnosed. Mediastinoscopy was performed in nine patients and confirmed in eight patients the initial combined EUS-EBUS-FNA diagnosis. The diagnosis was obtained in 91.2% with EUS-FNA, 70.6% with EBUS-FNA and 97% when combined procedure was performed. The overall sensitivity, specificity, positive and negative predictive values of EUS-EBUS-FNA for diagnosing malignancy were 96.5%, 100%, 100% and 90% respectively. No complications related to the procedure were observed. CONCLUSION: Combined EUS-EBUS-FNA represents an accurate technique in the diagnosis of MLN, can be done in a single time procedure and has the advantage of being less invasive than mediastinoscopy.

Relationship between placental traits and maternal intrinsic factors in sheep.

The relationship between maternal intrinsic factors and placental traits was investigated on three Southern Mediterranean breed of sheep; Cukurova Assaf (CA), Cukurova (C) and Cukurova Meat Sheep (CMS). The effect of parity and birth type were also considered in the study as a potential influencing factor. Our hypothesis was to show that while differences in placental traits between breed, parity and birth type affected lamb condition and survivability, its correlation to maternal intrinsic behavioral factors may also be a strong indicator. The study found breed related differences of maternal behavioral factors and also showed significant correlation of these behavioral patterns to various placental traits. It confirmed earlier findings that parity played a major role in the refinement of these behavioral patterns. Significant differences in birth weight (P<0.05), placental weight (P<0.05), number of cotyledons (P<0.01) and cotyledon length (P<0.05) was seen between breeds. Cotyledon weight (P<0.05), width (P<0.01) and length (P<0.05) were found to differ by parity. Breed and parity interaction significantly influenced cotyledon quantity. While we detected breed specific differences in relation to maternal intrinsic factors we also noticed significant variance within breeds to these behavioral patterns when linked to placental traits. Further study is required on the correlation between placental traits and postnatal behavior on not just the ewes but also on their lambs. This could have a significant bearing on how producers manage and maximize lamb survivability.

Placental traits and maternal intrinsic factors affected by parity and breed in goats.

The relationship between placental traits and maternal intrinsic factors of Saanen, German Fawn and Damascus goats was investigated. Data was collected from 93 goats. The results of the study demonstrated that there were positive correlations between placental weight (PW) and cotyledon number (CN) (r=0.498, P<0.01), cotyledon weight (CW) (r=0.880, P<0.01), cotyledon density (CD) (r=0.538, P<0.01), cotyledon width (CWI) (r=0.500, P<0.01) cotyledon length (CL) (r=0.414, P<0.01) and cotyledon density (CD) (r=0.278, P<0.05). CN was negatively correlated with placental efficiency (PE) (r=-0.421, P<0.01) and CD (r=-0.325, P<0.05). While expulsion of placenta, right teat length and cotyledon length were affected by parity of doe (P<0.05) birth weight (BW), CN, right teat diameter (RTD), left teat diameter (LTD), CD, and CL were affected by breed (P<0.01). Breed×parity was found significant both for expulsion time of placenta and left teat length (LTL) (P<0.05). Damascus goats had a significantly longer duration of licking and grooming events than others. Saanen was more likely to require birth assistance compared to the German Fawn.

Risk of malignancy in non-diagnostic thyroid fine-needle aspiration biopsy in multinodular goitre patients.

OBJECTIVE: Although the majority of biopsies is adequate for a cytological diagnosis, 5-20 % will be insufficient or nondiagnostic. Patients with nondiagnostic FNABs (ND-FNAB) may be further managed by continued observation, repeated FNAB, or thyroidectomy. The aim of this study was to determine the risk of malignancy in ND-FNAB, and to determine if there are any clinical factors that can be used to distinguish malignant versus benign disease in multinodular goitre patients with ND-FNAB. METHODS: A total of 411 multinodular goiter patients who underwent both a FNAB and thyroidectomy was the subject of study. Seventy nine of these patients with ND-FNAB were further reviewed retrospectively, and demographical and clinical factors were investigated to determine if there is any predictor of malignancy in this group of patients. Among these patients, FNAB has been repeated one more time in 5 (6.3 %) patients, and two more times in 9 (11.3 %) patients. RESULTS: Among 79 patients with ND-FNAB, 10 patients (12.6 %) had malignancy as found postoperatively. There were no differences in age, sex, functional status of the thyroid gland, and nodule size between patients with benign versus malignant disease. CONCLUSION: Nondiagnostic FNAB remains a significant problem in the evaluation of thyroid nodules. Despite ultrasound guidance, clinicians should inform patients that there is a 5-15 % malignancy risk of initial nondiagnostic specimens.

Oxidant and antioxidant activity in rabbit livers treated with zoledronic acid.

Zoledronic acid (ZA), a nitrogen-bearing bisphosphonate, is used to treat the hypercalcemia associated with cancer. In addition to its antiumor effects, it acts as an osteoclast inhibitor. To investigate the effects of ZA on oxidative stress and antioxidants, we studied reduced glutathione (GSH) and antioxidant gamma glutamate cysteine, including nitrite and nitrate, which are endproducts of nitric oxide (NO) as well as malondialdehyde (MDA) in rabbit liver tissue. In the study ZA (100 µg/kg) was administered to 7 rabbits that were fed ad libitum for comparison with untreated controls. MDA was studied using Thiobarbituric acid-reactive substance reduction, NO using cadmium reduction, GSH using an enzymatic method yielding dithinitrobenzene yellow substance. We observed significantly higher MDA and NO levels in the ZA group (P < .0001), whereas GSH levels were significantly lower (P < .0001). Tissues were examined histopathologically. According to our results we find ZA induced rabbit liver oxidative stress and decreases with antioxidant levels in liver tissue. Further studies are needed to explore the safe use of this agent.

DNA copy number aberrations in small-cell lung cancer reveal activation of the focal adhesion pathway.

Small-cell lung cancer (SCLC) is the most aggressive subtype of lung cancer in its clinical behavior, with a 5-year overall survival as low as 5%. Despite years of research in the field, molecular determinants of SCLC behavior are still poorly understood, and this deficiency has translated into an absence of specific diagnostics and targeted therapeutics. We hypothesized that tumor DNA copy number alterations would allow the identification of molecular pathways involved in SCLC progression. Array comparative genomic hybridization was performed on DNA extracted from 46 formalin-fixed paraffin-embedded SCLC tissue specimens. Genomic profiling of tumor and sex-matched control DNA allowed the identification of 70 regions of copy number gain and 55 regions of copy number loss. Using molecular pathway analysis, we found a strong enrichment in these regions of copy number alterations for 11 genes associated with the focal adhesion pathway. We verified these findings at the genomic, gene expression and protein level. Focal Adhesion Kinase (FAK), one of the central genes represented in this pathway, was commonly expressed in SCLC tumors and constitutively phosphorylated in SCLC cell lines. Those were poorly adherent to most substrates but not to laminin-322. Inhibition of FAK phosphorylation at Tyr(397) by a small-molecule inhibitor, PF-573,228, induced a dose-dependent decrease of adhesion and an increase of spreading in SCLC cell lines on laminin-322. Cells that tended to spread also showed a decrease in focal adhesions, as demonstrated by a decreased vinculin expression. These results support the concept that pathway analysis of genes in regions of copy number alterations may uncover molecular mechanisms of disease progression and demonstrate a new role of FAK and associated adhesion pathways in SCLC. Further investigations of FAK at the functional level may lead to a better understanding of SCLC progression and may have therapeutic implications.

Clinical significance of Hürthle cells in fine needle aspiration biopsy for multinodular goitre.

OBJECTIVE: So far, the significance of Hürthle cell predominance in fine needle aspiration biopsy (FNAB) in multinodular goitre (MNG) appears not definitely clarified. The aim of this study was to determine if there are any clinical factors that can be used to distinguish either malignant or benign disease with the aid of FNAB specimen that contains a predominance of Hürthle cells in multinodular goitre patients. METHODS: Among 623 patients who were evaluated for multinodular goitre between July 2004 and March 2009, 411 had a FNAB specimen. In 37 (9% of them) the FNAB specimen was interpreted as consistent with a Hürthle cell lesion. These patients comprised the study population and were reviewed retrospectively and their demographical and clinical factors were investigated to determine if there is any predictor of malignancy. RESULTS: Among 37 patients with Hürthle cell predominance in FNAB, 29 had benign diseases and 8 had malignant diseases resulting in 21.6% prevalence of malignancy. There were no differences in age, sex, functional status of the thyroid gland, and nodule size between patients with benign versus malignant disease. CONCLUSION: Total thyroidectomy should be recommended for all multinodular goitre patients with Hürthle cell predominance in FNAB, since there is no preoperative predictor of malignancy in these cases.

High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

Comparison of placental traits and their relation to litter size and parity weight in sheep.

The relationships between genotype and placental traits, parity and litter weight (LW), and factors affecting these characteristics were investigated in this study. In total, 112 ewes (Romanov crossbred and local breeds) were utilized. One-way ANOVA was used for statistical comparison, and a Pearson correlation was used to determine the relationships between the variables. Significant differences in parity weight within genotype and breed have been determined. A negative correlation was revealed between placental weight (PW) and placental efficiency (r = -0.743, P < 0.01; and r = -0.732, P < 0.01). There was no relationship between litter sex and placental traits. Birth type had a significant effect on PW (P < 0.05), and significant differences within sex-birth type interactions occurred (P < 0.05). The results of the present study have shown a positive correlation between cotyledon density and placental efficiency among all genotypes and breeds that were used in the study. In conclusion, it has been determined that placental traits were affected by LW and Romanov crossbreed ewes had greater PW than local breeds. Further studies are required to investigate the relationship between parity and placental traits in sheep.

Community-acquired urinary tract infections in Southern Turkey: etiology and antimicrobial resistance.

In this study, we compared the distribution and antibiotic susceptibility patterns of bacterial strains isolated from patients with community-acquired urinary tract infections in Southern Turkey, Hatay, during 2004 and 2005. The majority (82.3%) of the isolates were from women while the remaining (17.7%) were from men. Of all samples tested, 49% were culture-positive with a bacterial pathogen. The most frequently isolated bacterial species were Escherichia coli (45.1%), coagulase-negative Staphylococcus (CNS) (15.5%) and Klebsiella spp. (10.9%). E. coli was more prevalent in women (p < 0.05) while Klebsiella spp., Proteus spp. and Pseudomonas spp. were found more prevalent in men (p < 0.05). Increasing resistance to gentamicin, amikacin and cefazolin, and decreased resistance to ciprofloxacin, ofloxacin, levofloxacin and cotrimoxazole were observed in E. coli isolates over the 2 years. While the lowest resistance rates for E. coli occurred in 2004 (26.0%) and 2005 (20.5%) for cefuroxime, the highest resistance rates occurred in 2004 (81.3 and 47.9%) and 2005 (61.3 and 49.6%) for ampicillin and amoxicillin-clavulanate, respectively. The results of this study stress that antibiotic usage policies, especially empirical therapies, should be based on antimicrobial resistance surveillance studies.

Pulmonary arterial hypertension in a patient with stage II sarcoidosis and Hashitoxicosis.

Although pulmonary arterial hypertension is usually associated with advanced stages of sarcoidosis, its occurrence in early stage disease is rare. Herein, a case of associated pulmonary arterial hypertension in the setting of Hashitoxicosis and stage II pulmonary sarcoidosis is reported. The case of associated pulmonary arterial hypertension occurred in a young female without clinically significant medical history and who completely recovered after receiving oral corticotherapy only. Furthermore, this case report suggests the presence of an interaction between pulmonary arterial hypertension, sarcoidosis and Hashitoxicosis.

Dissection of the abdominal aorta in a child with Takayasu's arteritis.

Takayasu's arteritis is a chronic inflammatory disease that primarily involves the aorta and its main branches. Varying degrees of narrowing, occlusion, or dilatation develop in the involved vessel segments. However, dissection of the aorta is quite rare in this disease, and it may develop particularly after angioplasty. We report a very rare case of Takayasu's arteritis with dissection of the abdominal aorta just distal to the origin of the inferior mesenteric artery in a 9-year-old girl. She was treated conservatively with close follow-up. At the end of 1 year's follow-up, the dissection of the aorta did not show progression, and new lesions were not identified. To our knowledge, this patient is the youngest child presented with arterial dissection as the initial manifestation of the disease.