Retzius sparing robotic assisted radical prostatectomy vs. conventional robotic assisted radical prostatectomy: a systematic review and meta-analysis.

CONTEXT: Retzius sparing robotic assisted radical prostatectomy appears to have better continence rates when compared to conventional robotic assisted radical prostatectomy, however, concern with high positive surgical margin rates exist. OBJECTIVE: To systematically evaluate evidence comparing functional and oncological outcomes of retzius sparing robotic assisted radical prostatectomy and conventional robotic assisted radical prostatectomy. EVIDENCE ACQUISITION: The systematic review was performed in accordance with the Cochrane guidelines and the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Bibliographic databases searched were PubMed/MEDLINE, Cochrane central register of controlled trials-CENTRAL (in The Cochrane library-issue 1, 2018). We used the GRADE approach to assess the quality of the evidence. EVIDENCE SYNTHESIS: The search retrieved 137 references through electronic searches of various databases. Six were included in the review. RS-RALP was associated with better early continence rates (≤ 1 month) (moderate quality evidence) (RR 1.72, 95% CI 1.27, 2.32, p 0.0005) and at 3 months (low quality evidence) (RR 1.39, 95% CI 1.03, 1.88, p 0.03). Time to continence recovery, number of pads used and pad weight are better with RS-RALP. Based on very low quality evidence, RS-RALP did not alter 6 and 12 months continence rates. Based on very low quality evidence, RS-RALP did not alter T2 positive margin rates (RR 1.67, 95% CI 0.91, 3.06, p 0.10) and T3 positive margin rates (RR 1.08, 95% CI 0.68, 1.70, p = 0.75). Short-term biochemical free survival appears to be similar between the two approaches. Based on low-quality evidence, RS-RALP did not alter overall and major complication rates. CONCLUSIONS: RS-RARP appears to have earlier continence recovery when compared to Con-RARP which does not come at a significant oncologic cost. Whilst there was a trend towards higher PSM rates with RS-RALP, this did not achieve statistical significance. Furthermore this trend appeared to be less pronounced with T3 disease, where the PSM rates are almost similar.

Magnetic resonance imaging-directed transperineal limited-mapping prostatic biopsies to diagnose prostate cancer: a Scottish experience.

BACKGROUND: Transperineal prostatic biopsy is firmly established as an important tool in the diagnosis of prostate cancer. The benefit of additional imaging (magnetic resonance imaging) to target biopsy remains to be fully addressed. METHODS: Using a cohort of consecutive patients undergoing transperineal template mapping biopsies, we studied positive biopsies in the context of magnetic resonance imaging findings and examined the accuracy of magnetic resonance imaging in predicting the location of transperineal template mapping biopsies-detected prostate cancer. RESULTS: Forty-four patients (mean age: 65 years, range 53-78) underwent transperineal template mapping biopsies. Thirty-four patients had 1-2 and 10 patients had ≥3 previous transrectal ultrasound scan-guided biopsies. The mean prostate-specific antigen was 15 ng/mL (range 2.5-79 ng/mL). High-grade prostatic intraepithelial neoplasia was found in 12 (27%) patients and prostate cancer with Gleason <7, 7 and >7 in 13, 10 and 8 patients, respectively. Suspicious lesions on magnetic resonance imaging scans were scored from 1 to 5. In 28 patients, magnetic resonance imaging detected lesions with score ≥3. Magnetic resonance imaging correctly localised transperineal template mapping biopsies-detected prostate cancer in a hemi-gland approach, particularly in a right to left manner (79% positive prediction rate), but not in a quadrant approach (33% positive prediction rate). CONCLUSION: Our findings support the notion of magnetic resonance imaging-based selection of patients for transperineal template mapping biopsies and that lesions revealed by magnetic resonance imaging are likely useful for targeted biopsies.

Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome.

PURPOSE: Peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in glucose and lipid metabolism is one of the candidate genes associated with polycystic ovary syndrome (PCOS). We investigated individual and combined associations of Pro12Ala and His447His polymorphisms of PPARγ with PCOS susceptibility and its related traits (hyperinsulinemia, hyperandrogenemia and lipid parameters) in Indian women. METHOD: Genotyping of PPARγ polymorphisms in this case-control study was performed in PCOS (n = 450) and age-matched controls (n = 300) by direct sequencing. Clinical, anthropometric, hormonal and metabolic parameters were estimated in 275 women with PCOS and 169 controls. Chi-square test was used to compare the categorical data while regression analysis was used to evaluate association of genotypes with PCOS as well as its related phenotypes. RESULTS: The frequencies of CC and CG + GG genotypes of Pro12Ala (χ² = 15.3, p < 0.0001) and CC and CT + TT genotypes of His447His (χ² = 12.7, p = 0.0004) polymorphisms were significantly different between PCOS and controls. Logistic regression analysis revealed a significant association of PCOS with Pro12Ala but not the His447His polymorphism. Carriers of variant genotypes at both PPARγ loci showed significantly reduced 2 h glucose levels while carriers of variant His447His genotype showed lower fasting insulin and HOMA-IR levels in PCOS women. CONCLUSIONS: Pro12Ala polymorphism of PPARγ showed significant association with decreased PCOS susceptibility. Both polymorphisms influenced insulin related traits (2 h glucose, fasting insulin and HOMA-IR) and improved glucose metabolism in these women. This is the first report to establish that variations in PPARγ gene influence the insulin resistance pathophysiology in Indian women with PCOS.

Perioperative, Functional, and Oncologic Outcomes of On-Clamp Versus Off-Clamp Partial Nephrectomy: An Updated Meta-analysis of 9027 Patients.

OBJECTIVE: The aim of this study was to determine the comparative efficacy and safety between on-clamp and off-clamp partial nephrectomy in patients with renal masses. MATERIALS AND METHODS: This systematic review was pre-registered on The International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022339127). PubMed, Scopus, and Web of Science were searched. A manual search was also conducted to avoid missing relevant studies. All observational and experimental studies reporting the comparative efficacy and/or safety of on-clamp versus off-clamp partial nephrectomy were included. Outcomes were divided into 3 categories: perioperative, functional, and oncologic outcomes. Risk of bias was assessed using the The Risk Of Bias In Nonrandomized Studies of Interventions (ROBINS-I) and revised Cochrane ROB-II tool for nonrandomized and randomized studies, respectively. Fixed- and random-effect models were implemented to pool the mean difference and log odds ratio of continuous and dichotomous outcomes, respectively. A leave-one-out sensitivity analysis was conducted to determine if the effect size was driven by a single study, and Egger's regression test was used to assess publication bias. RESULTS: Forty-two studies were meta-analyzed. The on-clamping method showed greater benefit when compared to the off-clamping technique in terms of perioperative (estimated blood loss and blood transfusion), functional (estimated glomerular filtration rate), and oncologic outcomes (tumor resection time). However, it is associated with higher risk for complications. Most studies were of moderate-to-serious risk of bias. CONCLUSION: On-clamping shows superiority in terms of estimated blood loss, blood transfusion, estimated glomerular filtration rate, and tumor resection time. However, it is associated with increased risk of complications. The selection of the technique should be tailored per individual case based on their comorbidities and preoperative risk profile.

Association of vascular endothelial growth factor, transforming growth factor beta, and interferon gamma gene polymorphisms with proliferative diabetic retinopathy in patients with type 2 diabetes.

PURPOSE: Chronic hyperglycemia and hypoxemia are believed to be causal factors in the development of proliferative diabetic retinopathy (PDR) among individuals with type 2 diabetes. It is hypothesized that formation of new blood vessels in the retina due to prolonged hypoxia is associated with increased expression of several growth factors and angiogenic cytokines. In the present study, we investigated the association of genetic polymorphisms in vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-ß), and interferon γ (IFN-γ) genes, which may be responsible for the hypoxia-induced VEGF-mediated neovascularization pathway for the pathogenesis of PDR. METHODS: Our case-control association study composed of 493 ethnically matched volunteers (253 with PDR [cases] and 240 diabetic controls [DC]). Gene polymorphisms were determined with Taqman-based real-time PCR and amplification refractory mutation analysis system PCR. RESULTS: The VEGF-460C (rs833061C; p=0.0043) and IFN-γ +874T (rs2430561T; p=0.0011) alleles were significantly associated with PDR. CONCLUSIONS: Genetic variations at VEGF-460C and IFN-γ +874T might accelerate the pathogenesis of retinal neovascularization in PDR.

Association of tumor necrosis factor α, interleukin 6, and interleukin 10 promoter polymorphism with proliferative diabetic retinopathy in type 2 diabetic subjects.

PURPOSE: New blood vessel formation in the retina because of prolonged hypoxia is believed to be directly associated with increased expression of several growth factors and angiogenic cytokines. In the present study, we made an attempt to investigate the possible association of the promoter polymorphisms of interleukin 6, tumor necrosis factor α, and interleukin 10 for the pathogenesis of proliferative diabetic retinopathy (PDR). METHODS: This case-control study comprised 493 volunteers (253 PDR cases and 240 diabetic controls). Cases and controls were ascertained such that age, sex, nutrition, and glycemic status were matched. Genotypes were determined by polymerase chain reaction-based methods. RESULTS: Interleukin 10-1082GG (P = 0.0037; odds ratio [OR] = 2.232), tumor necrosis factor α-238AA (P = 0.0001; OR = 5.791), and GA (P = 0.0015; OR = 1.909) genotypes were significantly associated with PDR occurrence. The interleukin 10-1082G allele (P = 0.0048, OR = 1.4442) and the tumor necrosis factor α-238A allele (P = 0.0001; OR = 2.2897) were significantly increased among PDR cases. CONCLUSION: From our study, it may be concluded that the genetic variation, that is, tumor necrosis factor α-238A and interleukin 10-1082G alleles are the potent risk factors for the pathogenesis of PDR.

Trans-peritoneal vs. retroperitoneal robotic assisted partial nephrectomy in posterior renal tumours: need for a risk-stratified patient individualised approach. A systematic review and meta-analysis.

To systematically review world literature and compare peri-operative outcome including operating time (OT), estimated blood loss (EBL), warm ischemia time (WIT), length of stay (LOS) and complications between retroperitoneal robotic assisted partial nephrectomy (RP-RAPN) and trans-peritoneal robotic assisted partial nephrectomy (TP-RAPN) for posteriorly located renal masses. All randomised trials and observational studies comparing RP-RAPN and TP-RAPN for posteriorly located renal masses were considered. The GRADE approach (Grading of Recommendations Assessment, Development and Evaluation, GRADE) was used to rate the quality of evidence. 82 potential publications were identified. 3 were included in the review. All three studies were observational comparative studies. 347 and 550 patients underwent RP-RAPN and TP-RAPN, respectively, for posteriorly located tumours. There was statistically significant difference in LOS between the 2 techniques, favouring the RP-RAPN cohort: risk ratio (M-H, random, 95% CI), - 0.42 [- 0.67, - 0.18], p < 0.0006. There was no statistically significant difference in overall complication rates between the two techniques: risk ratio (M-H, fixed, 95% CI), 0.80 [0.49, 1.30], p = 0.37. There was no statistically significant difference in ≥ Clavien 3a complication rates between the two t echniques: risk ratio (M-H, fixed, 95% CI), 1.17 [0.62, 2.19], p = 0.63. OT, EBL, WIT and positive margin rates were similar for both approaches. The quality of evidence for complications, LOS and remaining outcomes were 'moderate', 'low' and 'very low', respectively, on GRADE approach. The current review suggests that the LOS with RP-RAPN are significantly lesser than TP-RAPN for posterior tumours. The RP-RAPN does not appear to offer any advantage over TP-RAPN for other peri-operative outcomes such as WIT, OT and EBL. The surgical margin rates and morbidity between the two approaches appear to be similar.

The influence of reaction temperature on the oscillatory behaviour in the palladium-catalysed phenylacetylene oxidative carbonylation reaction.

This paper reports the influence of reaction temperature on the occurrence and characteristics of pH oscillations that are observed during the palladium-catalysed phenylacetylene oxidative carbonylation reaction in a catalytic system (PdI2, KI, air, NaOAc) in methanol. Isothermal experiments were performed over the temperature range 10-50 degrees C. The experiments demonstrate that oscillations occur in the range 10-40 degrees C and that a decrease in reaction temperature results in an increase in the period and amplitude of the pH oscillations. Furthermore, it is observed that during oscillations at any specific temperature, the time taken for pH to increase from a minimum to a maximum value varies with respect to reaction time. However, the time required for the pH to fall from maximum to new minimum is approximately constant with respect to the reaction time and is a function of the reaction temperature.

Evidence supporting a role for the calcium-sensing receptor in Alzheimer disease.

The calcium-sensing receptor (CASR) is a G-protein coupled, transmembrane receptor that responds to changes in Ca(2+) levels. We hypothesized that the CASR could have a role in Alzheimer disease (AD) given expression of the CASR in brain, knowledge that calcium dysregulation promotes susceptibility to neuronal cell damage, the important role that the CASR plays in calcium regulation, and the fact that systemic calcium homeostasis and G-protein signal transduction are altered in AD patients. To investigate the association of CASR variation in AD susceptibility, we genotyped a polymorphic dinucleotide repeat marker within intron 4, one SNP within the promoter region and three non-synonymous SNPs within exon 7 of the CASR gene and tested for association analysis, using a well-characterized cohort of AD cases (n = 692) and controls (n = 435). The dinucleotide repeat polymorphism was significantly associated with AD status (OR = 1.62; 95% CI: 1.27-2.07, P = 0.00037, Bonferroni corrected P = 0.0011) and the three non-synonymous SNP haplotype was boarderline associated with AD status (P = 0.032, Bonferroni corrected P = 0.096). Stratifying by APOE4 allele carrier status revealed that the significant association was only in non-APOE4 carriers (OR of 1.90; 95% CI: 1.37-2.62, P = 0.0001). We also investigated whether apoE or beta amyloid could activate the calcium-sensing receptor. The receptor activation assays revealed that apoE as well as beta amyloid activated the CASR and that the level of activation appeared to be isoform dependent for apoE. These data support our hypothesis that the CASR has a role in AD susceptibility, particularly in individuals without an APOE4 allele.

The role of robotic surgery in the management of renal tract calculi.

The role of robotic assisted surgery in contemporary urolithiasis management is in its infancy. The mainstay in the management of renal tract calculi remains ureterorenoscopy (URS), extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PCNL). However, in rare clinical circumstances, such as large impacted pelvic and ureteric calculi, endo-urological techniques may not be adequate. Furthermore, patient may have a synchronous pathology such as pelvi-ureteric obstruction which preferably should be concurrently treated with the renal calculi in a single sitting. Robotic assisted laparoscopic ureterolithotomy (RALU), robotic assisted laparoscopic pyelolithotomy (RPL) with or without concurrent pyeloplasty and Robotic assisted laparoscopic anatrophic nephrolithotomy have all been described for complex stones. Additionally, technical challenges with a flexible ureteroscopy (FURS) have led to the development of robotic assisted flexible ureteroscopes. In the article we summarize the role of robotic assisted surgery in complex renal tract calculi.

Two-dimensional simple proportional feedback control of a chaotic reaction system.

The simple proportional feedback (SPF) control algorithm may, in principle, be used to attain periodic oscillations in dynamic systems exhibiting low-dimensional chaos. However, if implemented within a discrete control framework with sampling frequency limitations, controller performance may deteriorate. This phenomenon is illustrated using simulations of a chaotic autocatalytic reaction system. A two-dimensional (2D) SPF controller that explicitly takes into account some of the problems caused by limited sampling rates is then derived by introducing suitable modifications to the original SPF method. Using simulations, the performance of the 2D-SPF controller is compared to that of a conventional SPF control law when implemented as a sampled data controller. Two versions of the 2D-SPF controller are described: linear (L2D-SPF) and quadratic (Q2D-SPF). The performance of both the L2D-SPF and Q2D-SPF controllers is shown to be superior to the SPF when controller sampling frequencies are decreased. Furthermore, it is demonstrated that the Q2D-SPF controller provides better fixed point stabilization compared to both the L2D-SPF and the conventional SPF when concentration measurements are corrupted by noise.

Fourth branchial pouch sinus: A report of 7 cases and review of the literature.

A fourth branchial pouch sinus often manifests quite late in life as a recurrent neck abscess, suppurative thyroiditis, or pseudothyroiditis. Demonstration of the sinus opening in the piriform fossa by hypopharyngoscopy in combination with ultrasonography of the neck provides adequate information to justify proceeding to surgery. The sinus tract usually courses through the thyroid cartilage. The most effective treatment is surgical excision of the tract up to the piriform fossa through the cartilage. This procedure is associated with very low complication and recurrence rates. A fourth branchial pouch sinus is an uncommon condition. Even so, it is still underdiagnosed as a result of poor awareness of its existence by medical practitioners, including otolaryngologists. Part of the reason is a lack of adequate coverage of this topic in otolaryngology and surgery textbooks. In this article, we add to the literature by describing our experience with 7 patients-4 males and 3 females, aged 5 to 45 years (mean: 25.6)-who were diagnosed with a fourth branchial pouch sinus over a 6-year period. The diagnosis was confirmed by identifying the sinus opening at the apex of the piriform sinus during hypopharyngoscopy. Definitive treatment consisted of surgical exploration of the neck and excision of the tract.

Prevalence and age-wise distribution of Human Papillomavirus type 16/18 infections among hospital screened women of a peri-urban area in West Bengal: Impact of socio-demographic factors.

BACKGROUND: We undertook the current study on cervical Human Papillomavirus (HPV) prevalence along with cytology in women visiting the Gynecology Out-patient Department of a hospital for common gynecological ailments, subsequent to our earlier population-based study on HPV prevalence from India. METHODS: We analyzed data on cervical-cytology (Pap smears) and PCR-based molecular detection of HPV infection along with socio-demographic variables (N = 696). RESULTS: We identified 36.84% HPV-positive women amongst whom, HPV16 and 18 together predominated (79.37%) over other HPV types (20.63%). Contrarily, only 6.4% women revealed abnormal cytological lesions, of which, 46.51% were HPV-positive and 95% of such women harbored HPV16/18, while 5% harbored other HPV types. Individuals with normal cytology portrayed 36.09% HPV infections, of which, 77.97% were HPV16/18-positive and 22.03% harbored other HPV types. Overall HPV prevalence decreased significantly (ptrend  = 0.047) with increase in age, but HPV16/18 infections were significantly over-represented compared to the other HPV types across all age-groups. Specifically, HPV16 prevalence increased (p trend < 0.01) with increase in severity of cervical lesions. HPV16 prevalence did not differ between the Hindus and Muslims but HPV18 was significantly higher among the cytologically normal Muslim women (24.14%, p = 0.02), compared to the Hindus (11.91%), specifically among those ≥ 30 years of age. There was a significant (p < 0.05) overrepresentation of HPV16 prevalence among women who were users of oral contraceptive-pills, irrespective of cytology. CONCLUSIONS: Our study highlights the need for HPV16/18-based screening of cervical cancers in India considering the immense socio-cultural and genetic diversity at the population level.

Cell-intrinsic regulation of peripheral memory-phenotype T cell frequencies.

Memory T and B lymphocyte numbers are thought to be regulated by recent and cumulative microbial exposures. We report here that memory-phenotype lymphocyte frequencies in B, CD4 and CD8 T-cells in 3-monthly serial bleeds from healthy young adult humans were relatively stable over a 1-year period, while Plasmablast frequencies were not, suggesting that recent environmental exposures affected steady state levels of recently activated but not of memory lymphocyte subsets. Frequencies of memory B and CD4 T cells were not correlated, suggesting that variation in them was unlikely to be determined by cumulative antigenic exposures. Immunophenotyping of adult siblings showed high concordance in memory, but not of recently activated lymphocyte subsets. To explore the possibility of cell-intrinsic regulation of T cell memory, we screened effector memory-phenotype T cell (TEM) frequencies in common independent inbred mice strains. Using two pairs from these strains that differed predominantly in either CD4 TEM and/or CD8 TEM frequencies, we constructed bi-parental bone marrow chimeras in F1 recipient mice, and found that memory T cell frequencies in recipient mice were determined by donor genotypes. Together, these data suggest cell-autonomous determination of memory T niche size, and suggest mechanisms maintaining immune variability.

Dissecting host factors that regulate the early stages of tuberculosis infection.

Incomplete understanding of mechanisms involved in the host-pathogen interactions constrains our efforts to eliminate tuberculosis. In many individuals, resulting from immune response to mycobacterial infection organised structures called granulomas are formed. To identify host responses that may control at least the early stages of infection, we employed an in vitro granuloma model. Here, human PBMCs were infected with live Mycobacterium tuberculosis in culture, and the appearance of granuloma-like structures was monitored over the next several days. Production of cytokines and chemokines in culture supernatants was monitored at various times, and the resulting temporal profiles were examined for possible correlations with either granuloma formation, or bacterial growth. While a positive association of TNF-α and IFN-γ secretion levels with extent of granuloma formation could clearly be identified, we were, however, unable to detect any statistically significant relationship between any cytokine/chemokine and bacterial growth. Examination of specific host cellular biochemical pathways revealed that either modulation of neutral lipid homeostasis through inhibition of the Gi-protein coupled receptor GPR109A, or regulation of host metabolic pathways through addition of vitamin D, provided a more effective means of controlling infection. A subsequent genotypic analysis for a select subset of genes belonging to pathways known to be significant for TB pathology revealed associations of polymorphisms with cytokine secretions and bacterial growth independently. Collectively therefore, the present study supports that key metabolic pathways of the host cell, rather than levels of relevant cytokines/chemokines might be more critical for regulating the intracellular mycobacterial load, in the context of granuloma formation.

Hedgehog signaling pathway is active in GBM with GLI1 mRNA expression showing a single continuous distribution rather than discrete high/low clusters.

Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression--as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution-unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the "high-Hh" cluster of MB but 5.6 fold higher than that of the "low-Hh" cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 µM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them.

Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM.

Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy response in GBM is predetermined in its neoplastic clones via a specific set of mutations that alter relevant pathways. We describe exome-wide enrichment of variant allele frequencies (VAFs) in neurospheres displaying contrasting phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ-effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ-effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh) pathways in reversible TMZ-effect cells. Next, we validated the likely involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as well as on GBM patients, by extracting RNA-sequencing-based gene expression data from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ non-responder neurosphere in vitro by treating them with the FDA-approved pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate that the Hh-pathway impedes sustained TMZ-response in GBM and could be a potential therapeutic target to enhance TMZ-response in this malignancy.

Dysphagia due to forestier disease: three cases and systematic literature review.

Forestier disease or diffuse idiopathic skeletal hyperostosis (DISH) is an uncommon cause of dysphagia. Due to rarity of this condition there is neither any demographic data nor any consensus about the investigation and treatment modalities. Here an effort is made in the present article to compile the information regarding the demographic and clinical features, investigation modalities and different methods of treatment from all the available case reports of dysphagia due to Forestier disease in the English literature till date. Three cases of the same condition are also reported in the present paper. Three cases of dysphagia due to Forestier disease treated in the ENT department of R.G. Kar Medical College and Hospital are reported herewith. A systematic review of literature is also done. All the case reports of dysphagia due to Forestier disease are obtained by World Wide Web search (WWWS) using 'Forestier Disease', 'DISH' and 'dysphagia' as the key words. Data regarding age, sex, duration of the symptom, associated symptoms, investigations done, level of vertebrae involved and different modalities of treatment with result are collected and analyzed systematically. We found total 73 cases of dysphagia due to Forestier disease. The condition commonly affects males (M:F 5.64:1) in older age group (94.52% cases are 60 years or above), often presented to the treatment facility after a long time of initiation of the symptom. Barium swallow X-rays and lateral neck X-ray were the most common investigations done to arrive at a diagnosis as per result of systematic review. Surgical removal of the causative osteophytes were the definitive treatment, but if surgery is contraindicated, conservative measures like switchover to liquid and semisolid food and proper swallow training also improve the condition to some extent. Dysphagia due to Forestier disease mostly affects older male, often has a chronic course. It can be diagnosed with simple investigations like neck X-ray or barium swallow X-rays. The definitive treatment is surgical, but if contraindicated the problem can be palliated with simple measures like swallow training and change of food.

Migration of a fish bone from the upper aerodigestive tract to the skin of the neck: a case report.

We describe an unusual case of a migratory foreign body (fish bone) in the neck of a 45-year-old woman. The 2.1-cm bone migrated from the esophagus and traversed through the entire soft tissue of the neck, and it almost extruded through the skin of the neck. With the patient under local anesthesia, the foreign body was easily extracted through an incision over the skin.