Feasibility of abdominal fat quantification on MRI and impact on effectiveness of abdominal compression for radiotherapy motion management.

The impact of fat on abdominal compression effectiveness in abdominal cancers was determined using magnetic resonance imaging (MRI). Visceral and subcutaneous fat were delineated on T2W 3D MRI, and motion change with compression was measured on 2D cine MRI. Results from 16 participants showed no correlation between fat percentage, body mass index (BMI), and motion change. Median BMI was 28.7 (SD, 4.9). Mean motion reduction was 7.8 mm (IQR, 5.0; p = 0.001) with compression. While no direct link was found between fat, BMI, and compression effectiveness, abdominal compression remains crucial for motion management in radiotherapy planning, providing dosimetric benefits.

Co-enrichment of cancer-associated bacterial taxa is correlated with immune cell infiltrates in esophageal tumor tissue.

Esophageal carcinoma (ESCA) is a leading cause of cancer-related death worldwide, and certain oral and intestinal pathogens have been associated with cancer development and progression. We asked if esophageal microbiomes had shared alterations that could provide novel biomarkers for ESCA risk. We extracted DNA from tumor and non-tumor tissue of 212 patients in the NCI-MD case control study and sequenced the 16S rRNA gene (V3-4), with TCGA ESCA RNA-seq (n = 172) and WGS (n = 123) non-human reads used as validation. We identified four taxa, Campylobacter, Prevotella, Streptococcus, and Fusobacterium as highly enriched in esophageal cancer across all cohorts. Using SparCC, we discovered that Fusobacterium and Prevotella were also co-enriched across all cohorts. We then analyzed immune cell infiltration to determine if these dysbiotic taxa were associated with immune signatures. Using xCell to obtain predicted immune infiltrates, we identified a depletion of megakaryocyte-erythroid progenitor (MEP) cells in tumors with presence of any of the four taxa, along with enrichment of platelets in tumors with Campylobactor or Fusobacterium. Taken together, our results suggest that intratumoral presence of these co-occurring bacterial genera may confer tumor promoting immune alterations that allow disease progression in esophageal cancer.

Nutritional Management in Children and Adolescents with Severe Neurological Impairment-Who Cares? A Web-Based Survey Among Pediatric Specialists in Germany.

BACKGROUND: Nutritional management of children and adolescents with severe neurological impairment (SNI) is challenging. A web-based survey was distributed to identify the present situation and the knowledge of the involved medical professionals in Germany. METHODS: The survey was created with LimeSurvey, and access data were distributed by several medical societies. Eighty-three questions covered four topics: "general information," "gastro- and jejunostomy procedure," "handling of gastrostomies and feeding tubes," and "nutritional management and follow-up of children and adolescents with SNI." A descriptive analysis was performed with Microsoft Excel. RESULTS: A total of 156 participated (65 completed and 91 partially), 27% being pediatric gastroenterologists, 23% pediatric neurologists, and 10% pediatric surgeons. The most common indications for gastrostomy and tube feeding were oropharyngeal dysfunction and failure to thrive. Many patients were still underweight after some months of enteral feeding. The procedure of gastrostomy and handling recommendations varied broadly. Frequently, standard operating procedures (SOPs) and written local guidelines did not exist, and there was a considerable request for training. Only 53% of participants were aware of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition position paper published in 2017, even fewer (38%) followed the guidelines. The recommended measures to assess a nutritional status were often not respected. CONCLUSION: Nutritional management of children and adolescents with SNI in Germany is still strongly deficient. Despite the international guideline of 2017, few colleagues are aware of and adhere to the recommendations. This could be improved by interdisciplinary teaching and evaluation of the reasons for noncompliance. The procedure of gastrostomy and the patients' follow-up vary widely. Therefore, modified SOPs should be developed.

Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial.

AIMS: Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. MATERIALS AND METHODS: Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. RESULTS: Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. CONCLUSION: Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.

Outcome of percutaneous transhepatic biliary interventions in the management of biliary enteric anastomotic strictures with hepatolithiasis.

AIM: To evaluate percutaneous transhepatic biliary interventions (PTBI) using the ADDFREE (Access-Drain-Dilate-Flush-REpeat periodically-Evaluate and remove) technique and its outcomes in patients with biliary enteric anastomotic strictures (BEAS) and hepatolithiasis. MATERIAL AND METHODS: A retrospective review was undertaken of patients having hepatolithiasis with BEAS who underwent PTBI with a therapeutic intent (from January 2010 to January 2021) was performed. The technical and clinical successes of PTBI were analysed. Technical success was divided into duct access, crossing of BEAS, stricture resolution, and calculi clearance. Improvement of liver function tests, resolution of leucocytosis and presenting complaints were considered as clinical success. The patients were followed-up for a minimum duration of 6-months. RESULTS: Eighteen patients received PTBI in form of the ADDFREE technique. Hepatolithiasis was bilobar (44.4%), unilobar in multiple ducts (unilobar-m; 27.8%) and unilobar in a single duct (unilobar-s; 27.8%) along with anastomotic stricture. The average number of sessions of stone clearance for bilobar, unilobar-m, and unilobar-s was 4.4 (±1.6), 3.6 (±2.4), and 1.5 (±0.5), respectively. Clinical success was observed in 14 (77.8%), while one patient had recurrence of calculi and received repeat treatment. Bile culture was positive for bacterial organisms in 17 (94.4%) patients. No major complication were seen while minor complication were seen in five patients consisting of self-limiting haemobilia (n=1), per-catheter bile leak (n=2) and aggravation of cholangitis (n=2). CONCLUSION: PTBI, consisting of bile duct access, cholangioplasty, and calculi clearance, is a safe and effective technique for the treatment of patients having hepatolithiasis secondary to BEAS.

Particle trapped at the isotropic-nematic liquid crystal interface: Elastocapillary phenomena and drag forces.

We present numerical simulations of a particle trapped at the isotropic-nematic liquid crystal (Iso-N) interface. We use our recent model, based on a phase-field approach [see Qiu et al., Phys. Rev. E 103, 022706 (2021)10.1103/PhysRevE.103.022706], to couple the capillary forces acting on the interface with the elastic stresses in the nematic phase along with topological defects. A range of floating configurations are first investigated as a function of the contact angle and various anchoring conditions at the fluid interface. The results show that the response of the system is driven by the existence of an anchoring conflict at the contact line. Substantial particle displacements and/or interfacial deformations may occur in this case even for moderate anchoring strengths. These findings highlight the coupling between elastic and capillary forces. In a second part, we compute drag forces exerted on a particle that moves along the Iso-N interface for several contact angles and a moderate Ericksen number. Because of the coupling between the velocity and order parameter fields, topological defects are swept downstream of the particle by the flow and sometimes escape from the particle or merge with the interface. We also find linear force-velocity laws, with drag forces at the Iso-N interface being slightly greater than their isotropic counterparts due to director distortions. We discuss these results in light of past studies on the behavior of particles being dragged in the bulk of a liquid crystal matrix.

Effect of Race and Ethnicity on Risk of Radiotherapy Toxicity and Implications for Radiogenomics.

AIMS: Patient factors affect the risk of radiotherapy toxicity, but many are poorly defined. Studies have shown that race affects cancer incidence, survival, drug response, molecular pathways and epigenetics. Effects on radiosensitivity and radiotherapy toxicity are not well studied. The aim of the present study was to identify the effects of race and ethnicity on the risk of radiotherapy toxicity. MATERIALS AND METHODS: A systematic review was carried out of PubMed, Ovid Medline and Ovid Embase with no year limit. PRISMA 2020 guidelines were followed. Two independent assessors reviewed papers. RESULTS: Of 607 papers screened, 46 fulfilled the inclusion criteria. Papers were published between 1996 and 2021 and involved 30-28,354 individuals (median 433). Most involved patients with prostate (33%), breast (26%) and lung (9%) cancer. Both early and late toxicities were studied. Some studies reported a higher risk of toxicity in White men with prostate cancer compared with other races and ethnicities. For breast cancer patients, some reported an increased risk of toxicity in White women compared with other race and ethnic groups. In general, it was difficult to draw conclusions due to insufficient reporting and analysis of race and ethnicity in published literature. CONCLUSIONS: Reporting of race and ethnicity in radiotherapy studies must be harmonised and improved and frameworks are needed to improve the quality of reporting. Further research is needed to understand how ancestral heritage might affect radiosensitivity and risk of radiotherapy toxicity.

Using Real-world Data to Define a Validated Nomogram for Advanced Bladder Cancer Patients Who Respond to Immunotherapy.

AIMS: Immune checkpoint inhibitors (ICIs) are used in incurable urothelial cancers, both in chemo-naïve and platinum-refractory patients. Efficacy and toxicity data published outside controlled clinical trials are limited. We report overall survival, progression-free survival and toxicities of ICIs in locally advanced (LABC) or metastatic bladder cancer (MBC). We aimed to develop and validate a prognostic model for these patients. MATERIALS AND METHODS: A multicentre real-world individual patient-level data study (n = 272) evaluating ICIs in the first-line platinum-ineligible or platinum-refractory setting for LABC/MBC between March 2017 and February 2020 was undertaken. Cox regression analyses evaluated the association of prognostic factors with overall survival. Data were split to create a training (n = 208) and validation (n = 64) cohort. The backward elimination method with a P-value cut-off of 0.05 was used to develop a reduced prognostic model using the training data set. The concordance index and assessment of observed versus predicted survival probabilities were used to evaluate the final model. RESULTS: The median follow-up was 18.9 (15.8-21.5) months. The median overall survival and progression-free survival in the training cohort were 9.2 (95% confidence interval 7.4-10.5) and 4.5 months (3.5-5.7), respectively. The most common grade 1/2 adverse events recorded were fatigue (47.8%) and infection (19.9%). Five key prognostic factors found in the training set were low haemoglobin, high neutrophil count, choice of immunotherapy favouring pembrolizumab, presence of liver metastasis and steroid use within 30 days of treatment. The concordance index for the training and validation cohorts was 0.66 (standard error = 0.05) and 0.64 (standard error = 0.04), respectively, for the final model. A nomogram was developed to calculate the expected survival probabilities based on risk factors. CONCLUSIONS: Real-world data were used to produce a validated prognostic model for overall survival in LABC/MBC treated with ICIs. This model could assist in patient stratification, interpreting and framing future trials incorporating PD-1/PD-L1 inhibitors in LABC/MBC.

Translation of Prognostic and Pharmacodynamic Biomarkers from Trial to Non-trial Patients with Metastatic Castration-resistant Prostate Cancer Treated with Docetaxel.

AIMS: We conducted a pooled analysis of four randomised controlled trials and a non-trial retrospective dataset to study the changes in serum prostate-specific antigen (PSA) concentrations during treatment and its impact on survival in men treated with docetaxel for metastatic castration-resistant prostate cancer. We also compared the outcomes and pre-treatment prognostic factors between trial and non-trial patients. MATERIALS AND METHODS: Data were obtained from four randomised controlled trials and a non-trial cohort from a tertiary cancer centre. The PSA kinetics covariates chosen were absolute value (PSAT), best percentage change (BPCH) and tumour growth rate (K). The association between the covariates collected and overall survival was assessed within a Cox proportional hazards model. How well a covariate captured the difference between trial and non-trial patients was assessed by reporting on models with or without trial status as a covariate. RESULTS: We reviewed individual datasets of 2282 patients. The median overall survival for trial patients was 20.4 (95% confidence interval 19.6-22.2) months and for the non-trial cohort was 12.4 (10.7-14.7) months (P < 0.001). Of the pre-treatment factors, we found that only lactate dehydrogenase fully captured the difference in prognosis between the trial and non-trial cohorts. All PSA kinetic metrics appeared to be prognostic in both the trial and non-trial patients. However, the effect size was reduced in non-trial versus trial patients (interaction P < 0.001). Of the time-dependent covariates, we found that BPCH best captured the difference between trial and non-trial patient prognosis. CONCLUSIONS: The analysis presented here highlights how data from open-source trial databases can be combined with emerging clinical practice databases to assess differences between trial versus non-trial patients for particular treatments. These results highlight the importance of developing prognostic models using both pre-treatment and time-dependent biomarkers of new treatments.

Changes in Magnetic Resonance Imaging Radiomic Features in Response to Androgen Deprivation Therapy in Patients with Intermediate- and High-risk Prostate Cancer.

AIMS: The benefits of neoadjuvant androgen deprivation therapy (nADT) in the management of intermediate- and high-risk prostate cancer patients have been well-established. The aim of this study was to identify radiomic prognostic features derived from routine anatomic magnetic resonance imaging (MRI) sequences that can predict the response of the prostate cancer to nADT. MATERIALS AND METHODS: Patients with intermediate- and high-risk prostate cancer (with one of clinical stage ≥ T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) who received 3 months of ADT prior to radical external beam radiotherapy were enrolled into this study. The relative blood volume and the relative blood flow were used as dynamic MRI kinetic parameters to quantify vascular changes as responses to nADT. For all pre- and post-nADT data sets, a combination of T2-weighted and contrast-enhanced T1-weighted anatomic images were used to define regions of interest (ROI) as the dominant malignant nodules (DMNs) and the benign prostate (the entire prostate with the summed DMNs being subtracted). MRI textural radiomic features associated with prostate cancer response in the literature of energy and homogeneity were selected. Pyradiomics was used to extract textural features of the ROIs. A Wilcoxon signed-rank test was carried out to investigate if there were statistically significant differences in values of radiomic features between: (i) benign prostate ROI and DMN pre-nADT; (ii) pre- and post-nADT of benign prostate ROI; (iii) pre- and post-nADT of DMN. Changes in radiomic features and dynamic MRI kinetic parameters were correlated using the Spearman correlation test. RESULTS: Twenty prostate cancer patients were recruited into the study. The median time between the first baseline scan and the first on-treatment scan was 91.5 days (range 82-105). One patient had no discernible tumour visible, leaving 19 patients with evaluable data for the analysis. Baseline homogeneity and energy values differed significantly between benign and malignant tissue (P < 0.01). In response to nADT, homogeneity and energy showed reciprocal changes, significantly increased in benign prostate while decreasing in the DMN. The reduction in tumour homogeneity and energy feature values showed a positive association with the decline in tumour blood flow and tumour blood volume induced by androgen deprivation as derived from dynamic MRI parameters. CONCLUSION: Energy and homogeneity radiomic features derived from MRI of benign and malignant prostate showed significant reciprocal changes in response to nADT. This study confirms the potential of these radiomic features to act as surrogate markers of tumour androgen sensitivity due to their strong association with ADT-induced physiological effects in prostate tumours.

Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study.

AIM: To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS: After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION: cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.

Outcomes of ketorolac versus depomedrol infiltrations for subacromial impingement syndrome: a randomized controlled trial.

PURPOSE: Local subacromial infiltration with steroids is a common method of treatment of subacromial impingement syndrome. However, the use of steroids has concerns like tendon rupture, articular cartilage changes and infections. Local NSAIDs infiltration has recently been tried in literature. This study compares the effect of subacromial injections of ketorolac with steroids. METHODS: A randomized controlled study was planned with 35 patients in each group. Patients in group-1 were infiltrated with subacromial ketorolac (60 mg with 2% lignocaine) and in group-2 with a steroid (methylprednisolone-40 mg with 2% lignocaine). A similar rehabilitation protocol was followed, and clinical outcomes were analyzed using visual analog scale (VAS) for pain and shoulder pain and disability score (SPADI) and range of motion at one-month and three-months follow-up. RESULTS: Total data of 67 patients were analyzed, as three patients were lost to follow-up. In group 1, mean VAS improved from 7.9 [Formula: see text] 0.95 to 3.19 [Formula: see text] 0.81 (p < 0.001) and SPADI improved from 61.41 [Formula: see text] 11.86 to 28.91 [Formula: see text] 9.06 (p < 0.001) at three months, respectively. In group 2, mean VAS improved from 8.05 [Formula: see text] 0.94 to 2.9 [Formula: see text] 0.64 (p < 0.001) and SPADI improved from 63.45 [Formula: see text] 9.64 to 25.32 [Formula: see text] 6.87 (p < 0.001) at three months, respectively. However, there were no differences in functional outcomes between the groups (p = 0.21 for VAS, p = 0.16 for SPADI). CONCLUSION: Subacromial ketorolac infiltration has an equivalent outcome as that of steroid infiltration. Ketorolac could be considered as a reasonable alternative to steroids in cases where it is contraindicated.

Can honey improve the quality of cryopreserved cross bred ram semen added to tris egg yolk extender?

BACKGROUND: Honey can improve the quality of cryopreserved ram semen because of its multinutrient and cryoprotective nature added to standard tris egg yolk extender. OBJECTIVE: Different concentrations of honey were added to the standard tris egg yolk extender to improve the post-thaw quality of crossbred ram semen. METHOD: Thirty six (36) ejaculates from eight healthy cross bred rams were pooled and divided into four aliquots. Standard tris egg yolk extender without any alteration acted as Control (C) and was supplemented with different concentrations of honey, viz. T1 (honey 1.5%), T2 (2.5%), and T3 (3.5%). RESULTS: The percent (mean ± S.E.M) sperm motility at pre-freeze was significantly (P < 0.05) higher in Group T2 and at post-thaw in Group T3 in comparison to T1 and C treatment groups. The percent (mean ± S.E.M) HOST reacted spermatozoa at post-thaw was significantly (P < 0.05) higher in Group C and at pre-freeze the value was significantly (P < 0.05) higher in the same treatment group than Group T1. The mean MDA level (mean ± S.E.M) at post thaw was significantly (P < 0.05) lower in Group T3 than the treatment groups C and Group T1. CONCLUSION: From this study it is concluded that the addition of 3.5% honey to the standard tris egg yolk extender provides better protection to ram semen than the addition of 1.5% honey (i.e., Control). doi.org/10.54680/fr22610110212.

Systematic Review of Genomic Associations with Blood Pressure and Hypertension in Populations with African-Ancestry.

Background: Despite hypertension being highly prevalent in individuals with African-ancestry, they are under-represented in large genome-wide association studies. Inclusion of African participants is essential to better understand genetic associations with blood pressure-related traits in Africans. This systematic review critically evaluates existing studies with African-ancestry participants and identifies knowledge gaps. Methods: We followed the PRISMA protocol, HuGE Review handbook to identify literature on original research, in English, on genetic association studies for blood pressure-related traits (systolic and diastolic blood pressure, pulse and mean-arterial pressure, and hypertension) in populations with African-ancestry (January 2007 to April 2020). A narrative synthesis of the evidence was conducted. Results: Twelve studies with African-ancestry participants met the eligibility criteria, within which 10 studies met the additional genetic association data criteria (i.e., reporting only on African-ancestry participants). Across the five blood pressure-related traits, 26 genome-wide significantly associated SNPs were identified, with six SNPs linked to more than one trait, illustrating pleiotropic effects. Among the SNP associations, 12 had not previously been described in non-African studies. Discussion: The limited number of relevant studies highlights the dearth of genomic association studies on participants with African-ancestry, especially those located within Africa. Variations in study methodology, participant inclusion, adjustment for covariates (e.g., antihypertensive medication) and relatively small sample sizes make comparisons challenging, and have resulted in fewer significant associations, compared to large European studies. Regional variation in the prevalence and associated risk factors of hypertension across Africa makes a compelling argument to develop African cohorts to facilitate large genomic studies, using African-centric arrays. Data harmonisation and comparable study designs, such as described in the H3Africa CHAIR initiative, provide a good example toward achieving this goal. Other relevant information: SS and J-TB were funded by the South African National Research Foundation. MR is a South African Research Chair in Genomics and Bioinformatics of African populations hosted by the University of the Witwatersrand, funded by the Department of Science and Innovation, and administered by the NRF. This review was registered at PROSPERO (registration number: CRD42020179221) and OSF (registration DOI: 10.17605/OSF.IO/QT2HA).

The Role of Urinary LH and FSH in the Diagnosis of Pubertal Disorders.

BACKGROUND: Various hormonal parameters used to differentiate between different causes of pubertal disorders are invasive, cumbersome, and has variable sensitivity and specificity. Thus, the use of a noninvasive test like urinary gonadotropin for the diagnosis of pubertal disorders will offer a significant advantage. OBJECTIVE: To study the role of urinary gonadotropins (uLH, uFSH) for the diagnosis of various pubertal disorders and in the monitoring of Gonadotrophin releasing hormone, Hypothalamic-pituitary-gonadal (GnRHa) therapy in patients with central precocious puberty (CPP). MATERIALS AND METHODS: We evaluated 35 healthy children and 96 patients with disorders of puberty out of which 31 cases had early puberty and 65 cases had delayed puberty. We used Spearman's correlation coefficient to evaluate the correlation between the serum and urinary gonadotropins. We used Mann-Whitney U test (for 2 groups) and Kruskal-Wallis test (for > 2 groups) to compare the median urinary and serum gonadotropins of different groups. RESULTS: The urinary gonadotropins correlated strongly with serum gonadotropins in both healthy controls and individuals with pubertal disorders. The uLH level of ≥0.76 IU/L had 100% sensitivity and specificity to differentiate CPP from peripheral precocious puberty, whereas uLH level of ≥1.07 IU/L had 100% sensitivity and specificity for differentiating CPP from PT. In patients with delayed puberty, uFSH of ≥20.51 IU/L had 94.7% sensitivity and 91.3% specificity for the diagnosis of Hyper-Hypo cases and uLH level of ≥0.5 IU/L had sensitivity of 96.2% and specificity of 85% to differentiate constitutional delay in growth and puberty from hypogonadotropic-hypogonadism. In CPP patients on GnRHa therapy, the uLH level of ≥0.13 IU/L had 100% sensitivity and 86.7% specificity to identify those who had nonsuppressed serum LH levels. CONCLUSION: The urinary gonadotropins can be used as a reliable noninvasive test for the diagnosis of various pubertal disorders and also for monitoring of CPP patients on GnRHa therapy.

Curative-Intent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck in Sri Lanka: The Impact of Radiotherapy Technique on Survival.

AIMS: We conducted a retrospective analysis of patients with squamous cell carcinoma of the head and neck (SCCHN) treated with curative-intent radiotherapy at the National Cancer Institute of Sri Lanka to determine the impact of the treatment technique on disease-free survival (DFS). MATERIALS AND METHODS: SCCHN patients treated with radical radiotherapy or adjuvant postoperative radiotherapy from 2016 to 2017 were included in the study. Data on the following variables were collected by reviewing clinical and radiotherapy treatment records: age, gender, tumour site, stage, time to delivery of radiotherapy, use of neoadjuvant chemotherapy, use of concurrent radiosensitising chemotherapy and treatment technique. DFS, defined as the time to death, tumour recurrence or loss to follow-up, was the primary end point and outcomes were compared between patients treated with intensity-modulated radiotherapy (IMRT) in linear accelerators and those treated with conventional radiotherapy in cobalt teletherapy units. Univariate and multivariate analyses were carried out on known prognostic variables. RESULTS: In total, 408 patients were included in the study, with 138 (34%) being treated with IMRT in the linear accelerator. More than 75% of patients were of stage III or IV at diagnosis. The 2-year DFS of the whole cohort was 25% (95% confidence interval 21-30%). Patients treated with IMRT in the linear accelerator had a superior DFS in comparison with those treated with conventional radiotherapy in the cobalt teletherapy units (P < 0.001, hazard ratio 0.64, 95% confidence interval 0.5-0.82). Higher stage, cobalt treatment and use of neoadjuvant chemotherapy were adversely associated with DFS on multivariate analysis. CONCLUSION: A large proportion of patients with SCCHN treated with curative-intent radiotherapy in Sri Lanka had locally advanced disease and DFS was superior in patients treated with IMRT in the linear accelerator.

A practical approach to bladder preservation with hypofractionated radiotherapy for localised muscle-invasive bladder cancer.

Bladder preservation with trimodality treatment (TMT) is an alternative strategy to radical cystectomy (RC) for the management of localised muscle invasive bladder cancer (MIBC). TMT comprises of transurethral resection of the bladder tumour (TURBT) followed by radiotherapy with concurrent radiosensitisation. TMT studies have shown neo-adjuvant chemotherapy with cisplatin-based regimens is often given to further improve survival outcomes. A hypofractionated radiotherapy regimen is preferable due to its non-inferiority in local control and late toxicities. Radiosensitisation can comprise concurrent chemotherapy (with gemcitabine, cisplatin or combination fluorouracil and mitomycin), CON (carbogen and nicotinomide) or hyperthermic treatment. Radiotherapy techniques are continuously improving and becoming more personalised. As the bladder is a mobile structure subject to volumetric changes from filling, an adaptive approach can optimise bladder coverage and reduce dose to normal tissue. Adaptive radiotherapy (ART) is an evolving field that aims to overcome this. Improved knowledge of tumour biology and advances in imaging techniques aims to further optimise and personalise treatment.

Evaluation of Surgical Correction of Adolescent Idiopathic Scoliosis by Transpedicular Screws and Rods.

Transpedicular screw fixation is a challenging procedure for the correction of deformity of Adolescent Idiopathic Scoliosis (AIS) in the dorso-lumbar spine. The inadvertently misplaced screws have a high risk of complications. The exactness of the pedicle screws is normally distinct as the screws axis being fully enclosed within the cortices of the pedicle. Evaluation of the surgical correction of adolescent idiopathic scoliosis by transpedicular screws and rods was done in single posterior dynamic approach. This prospective observational study was conducted in the National Institute of Traumatology and Orthopedic Rehabilitation, Dhaka and different Hospitals in Dhaka, Bangladesh from July 2015 to March 2017. Ten patients at the age >9 years and <19 years who were admitted with a diagnosis of AIS during the period of study. The pedicle is a power nucleus of the vertebra and offers a secure grip of all 3 columns. Pedicle screw instrumentation has advantages of rigid fixation with improved 3D correction and it has been accepted as a reliable method with a high margin of safety. Accurate placement of the pedicle screws is important to reduce possible irreversible complication. So, all cases were corrected by transpedicular screws and rods in single posterior approach. In every case fusion was done in selected segments. In this study out of 10 patients 7(70.0%) were 10 to 14 years of age and 3(30.0%) were 15 to 18 years. Mean age 9.51±2.13 years. Minimum 10 years and maximum 18 years. Majority 7(70.0%) of the patients were female and the rest 3(30.0%) male. Five (50.0%) presented with level of involvement, 3(30.0%) patients thoracic and 2(20.0%) patients had lumbar. Maximum 7(70.0%) presented right sided involvement and rest 3(30.0%) left sided involvement. Before surgical intervention 100% patients had rib hump and positive Adams forward bending test, 70.0% patients had asymmetry of shoulder and uneven hip and also 50% patients had pain. After surgical treatment with transpedicular screws and rods through posterior approach, 70% of patients improved in terms of deformity. The average major curve deformity as defined by Cobb angle measurements was measured to be 54.9°±9.9° (40°-68°) in pre-surgery. After surgery this deformity corrected to 16.0°±4.9° (10°-24°) on average as measured in erect posture posterior anterior and lateral view. This represents significant improvement average of 71.4±4.3% (64.6-75.09) (p<0.001). This correction was maintained at 24 months after surgery. Functional results assessed by Modified Macnab criteria, significant number of 7(70.0%) patients had excellent outcome, 2(20.0%) patients had good outcome, 1(10.0%) patients had fair outcome and no poor outcome. Ninety percent (90%) patients had satisfactory results. No patient deteriorates neurologically after surgery. It is concluded that satisfactory curve correction and maintenance thereof is possible in adolescent idiopathic scoliosis, with posterior instrumentation by transpedicular screw and rods with effective reduction of cost and associated risks.