A FACS-based novel isolation technique identifies heterogeneous CTCs in oral squamous cell carcinoma.

Purpose: Isolating circulating tumour cells (CTCs) from the blood is challenging due to their low abundance and heterogeneity. Limitations of conventional CTC detection methods highlight the need for improved strategies to detect and isolate CTCs. Currently, the Food and Drug Administration (FDA)-approved CellSearch™ and other RUO techniques are not available in India. Therefore, we wanted to develop a flexible CTC detection/isolation technique that addresses the limitation(s) of currently available techniques and is suitable for various downstream applications. Methods: We developed a novel, efficient, user-friendly CTC isolation strategy combining density gradient centrifugation and immuno-magnetic hematogenous cell depletion with fluorescence-activated cell sorting (FACS)-based positive selection using multiple CTC-specific cell-surface markers. For FACS, a stringent gating strategy was optimised to exclude debris and doublets by side scatter/forward scatter (SSC/FSC) discriminator, remove dead cells by 4',6-diamidino-2-phenylindole (DAPI) staining, and eliminate non-specific fluorescence using a "dump" channel. APC-labelled anti-CD45mAB was used to gate remaining hematogenous cells, while multiple epithelial markers (EpCAM, EGFR, and Pan-Cytokeratin) and an epithelial-mesenchymal transition (EMT) marker (Vimentin) labelled with fluorescein isothiocyanate (FITC) were used to sort cancer cells. The technique was initially developed by spiking Cal 27 cancer cells into the blood of healthy donors and then validated in 95 biopsy-proven oral squamous cell carcinoma (OSCC) patients. CTCs isolated from patients were reconfirmed by Giemsa staining, immuno-staining, and whole transcriptome amplification (WTA), followed by qRT-PCR. In vitro culture and RNA sequencing (RNA-Seq) were also performed to confirm their suitability for various downstream applications. Results: The mean detection efficiency for the Cal 27 tongue cancer cells spiked in the whole blood of healthy donors was 32.82% ± 12.71%. While ~75% of our patients (71/95) had detectable CTCs, the CTC positivity was independent of the TNM staging. The isolated potential cancer cells from OSCC patients were heterogeneous in size. They expressed different CTC-specific markers in various combinations as identified by qRT-PCR after WTA in different patients. Isolated CTCs were also found to be suitable for downstream applications like short-term CTC culture and RNA-Seq. Conclusion: We developed a sensitive, specific, flexible, and affordable CTC detection/isolation technique, which is scalable to larger patient cohorts, provides a snapshot of CTC heterogeneity, isolates live CTCs ready for downstream molecular analysis, and, most importantly, is suitable for developing countries.

Upper limit of radiation treatment portals in rectal cancer: is it wise to keep using bony landmarks in the present era of 3D conformal treatment?

Background: This study aimed to compare the levels of L5-S1 interspace and the bifurcation of common iliac vessels on simulation images of rectal cancer patients to evaluate the adequacy of superior borders in conventional 2D planning for covering internal iliac vessels. Materials and methods: Simulation images of 236 rectal cancer patients who received neoadjuvant chemoradiation and surgery were analyzed. The images were retrieved from the radiation treatment database and included delineations of L5-S1 interspace and common iliac vessel bifurcation. Distances between these landmarks were measured. Results: Among the 236 patients, the majority had the common iliac artery bifurcation positioned above the L5-S1 interspace. Specifically, 78.3% of patients had the right common iliac bifurcation above L5-S1 interspace, with an average distance of 2.02 cm. For the left common iliac artery, 77.11% of patients had the bifurcation above L5-S1 interspace, with an average distance of 1.99 cm. Notably, there were cases where the bifurcations were not at the same level. Conclusion: Using the L5-S1 junction as the upper border of the treatment portal may result in missing proximal nodes at risk of metastases. However, further research is needed to determine the significance of failures above the L5-S1 interspace for justifying the inclusion of the common iliac artery bifurcation in the treatment portal.

Diabetic Foot Ulcer in India: Aetiological Trends and Bacterial Diversity.

Diabetes is one of the most prevalent epidemic metabolic disorders, responsible for a significant amount of physical, psychological and economic loss in human society. Diabetic foot ulcer (DFU) is one of the extreme pathophysiological consequences of diabetes. Bacterial infection is the most important cause of chronic DFU. Bacterial species or their biofilms show multidrug resistance, which complicates DFU and consequently leads to amputation of the infected part. Since the Indian population comprises diverse ethnic and cultural groups, this could influence the aetiology of diabetic foot infections and bacterial diversity. We reviewed 56 articles published from 2005 to 2022 on the microbiology of DFU and extracted the data on study location, number of patients analysed in the study, pathophysiological complications, age of the patients, sex of the patient, type of bacteria, type of infection (mono or polymicrobial), predominant bacteria (Gram-positive or Gram-negative), predominant isolates and multiple drug resistance (tested or not). We analysed data and described aetiological trends in diabetic foot infections and bacterial diversity. The study revealed that Gram-negative bacteria are predominant as compared to Gram-positive bacteria in individuals with diabetes with DFU in India. Escherichia coli, Pseudomonas aeruginosa, Klebsiella sp. and Proteus sp. were the most predominant Gram-negative bacteria, while Staphylococcus aureus and Enterococcus sp. were the major Gram-positive bacteria in DFU. We discuss bacterial infections in DFU in the context of bacterial diversity, sampling methods, demography and aetiology.

Efficacy of adjuvant radiation in early-stage cancers of buccal mucosa: an institutional experience.

PURPOSE: The purpose of this study is to determine if depth of infiltration is the only risk factor that will determine the outcomes in early-stage buccal mucosa patients or do the other minor risk factors have an impact too. METHODS: It is a retrospective analysis of 226 patients with early-stage buccal mucosa cancer who were treated with curative intent from 2010 to 2020. These patients were grouped in two arms, surgery alone (n = 111) and surgery followed by adjuvant radiotherapy (n = 115). Patients were followed up and local and regional recurrences and distant metastasis were recorded. RESULTS: Our results show that addition of radiation to the standard surgery arm improves overall survival and disease-free survival, though the improvement in overall survival was not statistically significant. This improvement was more pronounced in the depth of infiltration > 5 mm and in 5 mm or less depth of infiltration this benefit was not statistically significant. Other factors like perineural invasion, lymphovascular invasion, tumour size, node positive, margin positive were considered for univariate analysis. Although there was a trend towards improvement of OS and DFS, it was not statistically significant as far as these factors are concerned. CONCLUSION: The role of adjuvant radiation in early-stage cancers of buccal mucosa is a crucial tool with definitive DFS benefit and requires more prospective trials to answer the OS benefit.

Case study of rainfall and temperature assessment through trend and homogeneity analyses in Vadodara and Chhotaudepur district of Gujarat State, India.

This study aims to assess the climate change impact on the rainfall and temperature data of the Vadodara-Chhotaudepur district of India and to focus on the environmental challenges related to the rainfall and temperature in the present state of development, land use, industrialization, and urbanization. The study utilized nine trend analysis methods, namely linear regression (LR), Sen's robust slope estimator (SS), Mann-Kendall test (MK), Spearman's rank correlation (SRC), the trend-free pre-whitening (TFPW), variance correction approach by Hamed and Rao (1998) with MK test (MK-CF1), variance correction approach by Yue and Wang (2004) with MK test (MK-CF2), block bootstrap with MK test (BBS-MK), and graphical method as innovative trend analysis (ITA), applied on monthly, annual, and seasonal scales. Additionally, the study also employed four homogeneity analysis methods, including Pettitt's test, standard normal homogeneity test (SNHT), Buishand's test, and Von Neumann Ratio test (VNRTs). The IMD (Indian meteorological department) gridded long-term rainfall data from 1901 to 2019 and temperature data from 1951 to 2019 are used in the present study to assess the homogeneity and trends of the data series. Results showed a warming trend of maximum temperature (MaxT) and minimum temperature (MinT) at the monthly, annual, and seasonal time scale and significant (at 5%) warming trend in annual MinT in the entire study area. Annual rainfall showed negative trend in the study area with significant (at 5%) negative trend in eastern deforested area western industrial and area adjacent to thermal power station. The change point is detected in annual rainfall time series in eastern forest area in 1959 and western area in 1983, i.e., after development of the industries and commissioning of thermal power station in the western study area. The trend rate of MaxT and MinT has been recognized as 0.004 °C/year and 0.019 °C/year, respectively, for the data period of 1951 to 2019. The annual rainfall trend rate has been observed as -0.743 mm/year for the data range 1901 to 2019. All trend analysis methods revealed consistent results except MK-CF2 method, which portraits greater number of significant trends in trend analysis methods.

An experience with simultaneous integrated boost-volumetric-modulated arc therapy in the definitive treatment of head and neck cancer: An Indian data.

Background: There are very few prospective studies comparing simultaneous integrated boost versus sequential boost in the setting of definitive treatment modality of head and neck squamous cell cancer (HNSCC), especially in the Indian scenario. Materials and Methods: We prospectively randomized 50 patients with biopsy-proven squamous cell carcinoma of the oropharynx, hypopharynx, and larynx malignancies, stage T1-3, enlarged node measuring ≤3 cm that are planned for definitive radiotherapy with chemotherapy into either hypo-fractionated simultaneous integrated (Hypo-SIB VMAT) boost arm or conventional (Conv-VMAT) boost arm. Results: Most of the patients were men and aged less than 50 years. Patients with nodal involvement were 76% in Hypo-SIB VMAT and 80% in Conv-VMAT arm. The overall stage group distribution of II, III, and IVA were 16%, 44%, 40%, and 12%, 56%, and 32%, respectively, in both arms. All patients completed the intended treatment in both arms. Overall survival at the end of 2 years was 84% in Hypo-SIB VMAT arm and 80% in the Conv-VMAT arm (P = 0.25); disease-free survival (DFS) was 88% and 72%, respectively (P = 0.12); and locoregional recurrence-free survival (LRFS) was 92% and 84%, respectively (P = 0.38). All the acute and chronic toxicities in both the arms were comparable with no significant difference in any of the toxicities. The average overall treatment time (OTT) in Hypo-SIB VMAT arm is 39.4 days and in Conv-VMAT arm is 50.2 days (P = 0.00001) which is statistically significant. Conclusions: Accelerated Hypo-SIB VMAT has similar response and toxicities as compared to Conv-VMAT in the setting of definitive concurrent chemoradiation of HNSCC patients with the advantage of less OTT, faster treatment delivery, and patient compliance.

Genomic instability detected from the saliva of Head and Neck Squamous Cell Carcinoma patients: Association with clinical implications.

OBJECTIVES: Genomic instability in cancers is often associated with poor disease outcomes. In Head and Neck Squamous Cell Carcinoma (HNSCC), saliva being the contact fluid contains cancers cells shed from the primary tumour. This study detected genomic instability from cancer cells shed in saliva and correlated the same with clinical implications. DESIGN: Genomic instability in HNSCC patients (n = 81) was analysed and compared with control subjects (n = 30). Alu sequences were amplified from the DNA of the cells shed in saliva and from the blood (Germline DNA) using Alu-PCR. Band variations between amplified products of salivary cells' DNA and germline DNA were compared. 'Instability Score' was calculated by counting the band variation(s). The 'Instability Score' was further used as a measure of genomic instability. RESULTS: Higher instability was detected in patients as compared to the controls (p < 0.0001). After treatment, there was a significant decrease (p < 0.0001) in the Instability score and patients with higher instability scores responded better to radiotherapy. The patient group consuming both tobacco and alcohol had a higher instability score in comparison to the tobacco group (p = 0.0056). Also, Instability scores are inversely correlated with nodal metastasis (p = 0.0075). A high Instability score before treatment resulted in a better prognosis in HNSCC patients (HR: 1.8, 95%CI: 1.024-3.164, p = 0.0306). CONCLUSION: Our data suggest that genomic instability estimated from the tumour cells shed in the saliva of HNSCC patients by amplifying Alu sequence (Alu-PCR) is associated with radiotherapy response.

Peripheral Nerve Blocks Outperform General Anesthesia for Pain Control in Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-analysis.

PURPOSE: The purpose of this review is to compare the effectiveness of different peripheral nerve blocks and general anesthesia (GA) in controlling postoperative pain after arthroscopic rotator cuff repair (ARCR). METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review was conducted for the period of January 1, 2005, to February 16, 2021, by searching the following databases: PubMed, Cochrane, Embase, and Arthroscopyjournal.org. The primary outcomes of interest included 1-hour, 24-hour, and 48-hour pain scores on a numeric rating scale or visual analog scale (VAS). Inclusion criteria were English language studies reporting on adults (≥18 years) undergoing ARCR with peripheral nerve blockade. To synthesize subjective pain score data at each evaluation time point across studies, we performed random-effects network meta-regression analyses accounting for baseline pain score as a covariate. RESULTS: A total of 14 randomized controlled trials with 851 patients were included in the meta-analysis. Data from six different nerve block interventions, single-shot interscalene brachial plexus nerve block (s-ISB; 37.8% [322/851]), single-shot suprascapular nerve block (s-SSNB; 9.9% [84/851]), continuous ISB (c-ISB; 17.5% [149/851]), continuous SSNB (c-SSNB; 6.9% [59/851]), s-ISB combined with SSNB (s-ISB+SSNB; 5.8% [49/851]), s-SSNB combined with axillary nerve block (s-SSNB+ANB; 4.8% [41/851]), as well as GA (17.3% [147/851]) were included. Our meta-analysis demonstrated that c-ISB block had a significant reduction in pain score relative to GA at 1-hour postoperation (mean difference [MD]: -1.8; 95% credible interval [CrI] = -3.4, -.08). There were no significant differences in VAS pain scores relative to GA at 24 and 48 hours postoperatively. However, s-ISB+SSNB had a significant reduction in 48-hour pain score compared to s-ISB (MD = -1.07; 95% CrI = -1.92, -.22). CONCLUSIONS: It remains unclear which peripheral nerve block strategy is optimal for ARCR. However, peripheral nerve blocks are highly effective at attenuating postoperative ARCR pain and should be more widely considered as an alternative over general anesthesia alone. LEVEL OF EVIDENCE: Level II Systematic review and meta-analysis of Level I and II studies.

Corrigendum: Formulation and development of transferrin targeted solid lipid nanoparticles for breast cancer therapy.

[This corrects the article DOI: 10.3389/fphar.2020.614290.].

Impact of nodal boost irradiation and MR-based brachytherapy on oncologic outcomes in node-positive cervical cancer.

This study aimed to prospectively evaluate the impact of dose-escalated irradiation of nodal metastases on clinical outcomes compared to no boost in patients with node-positive, bulky, locally advanced cervical cancer (LACC) undergoing standard chemoradiation and MRI-based brachytherapy. METHODS: This comparative study included 161 patients with node-positive LACC treated with definitive chemoradiation and MRI-based brachytherapy. The prospective Boost arm accrued 71 patients to receive nodal boost either sequentially or simultaneously to an equivalent dose of 60 Gy. The control arm comprised 90 patients treated before this protocol period with no additional nodal boost. RESULT: Baseline patient and tumor characteristics were similar in both groups. All patients had at least one tumor dimension >5 cm at presentation, and 31% had para-aortic node involvement. With a median follow-up of 36 months (IQR:19-50.5), the overall 3-year Local control rate was 88.8%. The 3-year Regional control (93% vs. 80%, p = 0.035) was statistically better in the Boost arm. No nodal failure was observed in nodes <3 cc and < 2 cm, even in the No-boost arm. There was no significant difference in Disease-free survival (67.6% vs. 58.9%,p = 0.454) and Overall Survival (78.9% vs. 74.4%,p = 0.87) between the two arms. Incidence of acute or late toxicities did not differ significantly with nodal boost or the boost delivery technique. CONCLUSION: The addition of external radiation nodal boost to standard treatment of high-volume cervical cancer has improved pelvic control with an acceptable rate of toxicities. However, high systemic failures continue to pose a challenge in improving survival outcomes.

Comparison of treatment response in cervical carcinoma patients infected with human papillomavirus 16 and human papillomavirus 18 who are treated with chemoradiation.

OBJECTIVES: The primary objective of this study was to compare the treatment response of cervical carcinoma patients infected with human papillomavirus (HPV) 16 and HPV 18 who are treated with chemoradiation. MATERIALS AND METHODS: Ninety-six biopsy-proven cervical cancer patients, suitable for curative treatment with definitive radio-chemotherapy with International Federation of Gynecology and Obstetrics Stage IB2-IIIB, were included in this prospective study. HPV testing was done using TRUPCR® HPV 16 and 18 real-time polymerase chain reaction kit. All the patients received a dose of 83-90 Gy total equieffective dose to the high risk clinical target volume(HRCTV) using tele- and brachytherapy. RESULTS: Of the 96 patients, 79 (82.3%) patients were positive for HPV DNA. Seventy-three patients showed HPV genotype 16 positivity and six patients were positive for genotype 18. The response was correlated with HPV genotype. There was a statistically significant increase in complete radiological response in HPV 16 compared to HPV 18 and negative groups at 3 months, 80.8%, 50%, and 52.9%, respectively (χ2 = 36.5, P < 0.001). There was also a statistically significant increase in clinical response at 3 months in HPV 16 group compared to HPV 18 and negative groups, 87.5%, 50%, and 50%, respectively (χ2 = 29.9, P < 0.001). The age, volume of the disease, overall treatment time, average hemoglobin level, and the number of blood transfusions did not have any correlation. CONCLUSION: HPV genotype 16 positivity shows higher complete response in cervical carcinoma patients treated with definitive chemoradiation compared to HPV 18 genotype. Further HPV genotyping could potentially help stratify cervical cancer patients for more effective therapeutic regimens.

Cognitive deficits among patients surviving aneurysmal subarachnoid hemorrhage. A contemporary systematic review.

BACKGROUND: Subarachnoid hemorrhage (SAH) is associated with high rates of morbidity, including neurological and cognitive deficits that may be difficult to identify and quantify. This review provides an update on the cognitive deficits that may result from spontaneous aneurysmal SAH (aSAH) and identifies factors that may help predict and manage these deficits at discharge and thereafter. MATERIALS AND METHODS: We conducted a systematic review of PubMed and Google Scholar to identify studies published between 2010 and 2019 that assessed cognitive deficits at discharge and during follow-up in patients with aSAH. Full-text articles were assessed for information regarding cognitive testing and factors that may be associated with functional outcomes in this population. RESULTS: We reviewed 65 studies published since 2010 that described the cognitive deficits associated with non-traumatic aSAH. Such deficits may impact functional outcomes, quality of life, and return to work and may result in cognitive impairments, such as memory difficulties, speech problems, and psychiatric disorders. CONCLUSIONS: Patients with aSAH, even those that appear normal at the time of hospital discharge, may harbor cognitive deficits that are difficult to detect, yet can interfere with daily functioning. Further research is needed to provide additional information and to identify stronger correlations to be used in the identification, treatment, and amelioration of long-term cognitive deficits in aSAH patients, including those who are discharged with good clinical outcomes scores.

Evaluation and evolution of apparent diffusion coefficient (ADC) in image-guided adaptive brachytherapy (IGABT) for cervical cancer.

PURPOSE: Image-guided adaptive brachytherapy (IGABT) recently has shown excellent clinical outcomes with superior local control and less toxicity. For IGABT, T2W (T2-weighted) MRI is the gold standard. However, studies have shown that target delineation with the same results in uncertainties, poor interobserver variabilities, and low conformity indices for high-risk clinical target volume contours. In this study, we investigate the role of diffusion-weighted imaging-derived apparent diffusion coefficient (ADC) maps to aid in IGABT. We also evaluated ADC from the baseline to brachytherapy. METHODS AND MATERIALS: Thirty selected patients were enrolled for this study, and two MRIs were taken at diagnosis and before brachytherapy. Patients were divided into two groups, Group 1 being patients with parametrial involvement before external beam radiotherapy and no parametrial involvement before brachytherapy. Group 2 included patients with parametrial involvement before external beam radiotherapy and persistent parametrial involvement before brachytherapy. ADC was measured at the center, edge, and 1 cm from the edge. RESULTS: The measured ADC increased from diagnosis to brachytherapy, and this increase was more for the patients in Group 1 than in Group 2. The mean TDadc (diagnosis ADC, center), TEadc (tumor edge ADC diagnosis), and T1cmDadc (1 cm from edge at diagnosis) were 0.884, 1.45, and 1.9 × 10-3 mm2/s, respectively. The TBadc (ADC at brachytherapy, center), TEBadc (tumor edge ADC at brachytherapy), and TE1cmBadc (1 cm from edge brachytherapy) were 1.2, 1.8, and 2.3 × 10-3 mm2/s, respectively, p-value <0.00001. No abnormal ADC was present outside the high-risk clinical target volume contours. CONCLUSION: MRI-based IGABT using T2W imaging essentially covers all functionally abnormal zones at brachytherapy. Diffusion-weighted imaging, along with ADC maps, should only be used as a supplement for target delineation.

A comparative study evaluating the dose volume parameters in 3D conformal radiation of left sided whole breast irradiation including regional lymphnodes - a need of resource constrained countries.

BACKGROUND: The purpose of this study was to compare four 3D conformal radiation techniques in treatment of left breast cancer patients. MATERIALS AND METHODS: Radiation was planned for 20 patients to the left breast and regional lymph nodes using four techniques: partially wide tangents, photon-photon mix, photon-electron mix and 30/70 photon-electron mix. All plans were evaluated for internal mammary nodes (IMN) coverage, hotspot and normal tissue constraints. RESULT: The 85% of planning target volume (PTV) coverage was lesser for upper IMN than the lower IMN (below the lower border of the clavicular head) for all four techniques. The lower IMN coverage was better for partially wide tangent (80.46%) and photon-photon mix (88.88%). The lowest value of hotspot was seen in the partially wide tangent technique (112.69% ± 1.92). Hotspot is unacceptably high in both photon-electron mix and 30/70 photon-electron mix (> 120%). Left lung mean dose for all techniques on a pair-wise comparison showed no statistical difference. Left lung V20 values for partially wide tangent was 37.56% ± 8.17 and for photon-photon mix it was 40.49% ± 3.36. The mean heart dose with partially wide tangent was 9.43 ± 3.15 Gy and with photon-photon mix it was 10.10 ± 2.70 Gy. The mean heart dose for photon-electron mix was 7.56 ± 1.95 Gy and for 30/70 photon-electron mix it was 7.98 ± 2.16 Gy. CONCLUSION: No single technique satisfies all the criteria. The decision should be made on a case-by-case basis, considering the anatomy of the patient, availability of electron facilities and setup accuracy and reproducibility.

Formulation and Development of Transferrin Targeted Solid Lipid Nanoparticles for Breast Cancer Therapy.

Breast cancer is conventionally treated by surgery, chemotherapy and radiation therapy followed by post operational hormonal therapy. Tamoxifen citrate is a best option to treat breast cancer because its selective estrogen receptor modulation activity. Owing to its antiestrogenic action on breast as well as uterine cells, Tamoxifen citrate shows uterine toxicity. The dose 20 mg per day of Tamoxifen citrate required to show therapeutic effect causes side effects and toxicity to vital organs such as liver, kidney and uterus. In the present study, transferrin-conjugated solid lipid nanoparticles (SLNs) were successfully prepared to enhance the active targeting of tamoxifen citrate in breast cancer. Developed formulations were evaluated for particle size, surface charge, surface morphology and in vitro dissolution studies. Developed formulations exhibited more cytotoxicity as compared to pure Tamoxifen citrate solution in time as well as concentration dependent manner on human breast cancer MCF-7 cells. Further, cell uptake and flow cytometry studies confirmed the qualitative uptake of developed D-SLN and SMD-SLN by human breast cancer MCF-7 cells. Overall, proposed study highlights that transferrin engineered nanocarriers could enhance the therapeutic response of nanomedicines for breast cancer treatment.

A prospective comparative dosimetric study between diffusion weighted MRI (DWI) & T2-weighted MRI (T2W) for target delineation and planning in cervical cancer brachytherapy.

AIM: To evaluate the difference between GTVBT (Gross Tumor Volume at Brachytherapy) and HR CTV (High Risk Clinical Tumor Volume) delineated with DWI and T2W MRI. To evaluate doses to organs at risk and targets from plans generated using T2W and DWI. BACKGROUND: Functional imaging with DWI can improve cervical tumor distinction as it is more sensitive than T2W MRI even in detecting parametrial invasion. This study does a dosimetric comparison between a T2W and DWI based plan. METHODS: Fifty carcinoma cervix patients were subjected to MRI based brachytherapy. T2W and a diffusion weighted sequence were acquired. Target delineation and brachytherapy planning was done on both T2W and DWI. Standard DVH parameters were recorded and the treatment was given using the plan generated from T2W images. RESULTS: GTVBT and HRCTV contours on DWI were different when compared with T2W. Mean GTVBT volume on T2W and DWI was 5.25 and 5.23, respectively (p value 0.8). Mean HRCTV on T2W and DWI was 28.3 and 27 cc, respectively (p value 0.003). Planning on the above volumes resulted in a superior coverage in terms of HRCTV D90 and D100 for DWI based plan, HRCTV D90 - 735.1 and 741 cGy for T2W and DWI, respectively (p value 0.006), HRCTV D100 - 441.05 and 444.5 for T2W and DWI plans, respectively (p value = 0.006). Doses to the OAR were not significantly increased. CONCLUSION: GEC ESTRO based contouring guidelines cover all the functionally abnormal areas on DWI. DWI should only be used as a supplement to T2W for contouring target volumes.

Superficial temporal artery to middle cerebral artery (STA-MCA) bypass via retrograde arterial anastomosis in a patient with common carotid artery occlusion: a case report.

The standard superficial temporal artery to middle cerebral artery (STA-MCA) bypass depends on adequate antegrade flow in the STA. In the setting of occlusion of the common or external carotid arteries, revascularization requires modification of the standard bypass procedure. A patient with prior history of irradiation for head and neck carcinoma presented with an ischemic injury and fluctuating neurologic deficit not responsive to medical therapy. His left common carotid artery was occluded, but angiographic evaluation demonstrated retrograde filling of his left STA. Reverse STA-MCA bypass was performed, taking advantage of spontaneous collateralization which allowed for retrograde filling of the STA.

Long-term effectiveness and safety of image-based, transperineal combined intracavitary and interstitial brachytherapy in treatment of locally advanced cervical cancer.

PURPOSE: The aim of the study was to evaluate the impact of image-based combined intracavitary-interstitial brachytherapy (IC-ISBT) using a transperineal template in locally advanced cervical cancer treatment. METHODS AND MATERIALS: A total of 94 patients of cervical cancer stage IIB-IVA underwent image-based transperineal interstitial brachytherapy without tandem (ISBT) or with tandem (IC-ISBT) between June 2008 and June 2018 at our institution. After pelvic chemoradiation, 42 patients underwent ISBT and 52 IC-ISBT. Dosimetric data, clinical response, and toxicity records of these patients were reviewed. RESULTS: Clinical stage distribution was as follows: IIB: 22.4% (21), IIIA: 10.6% (10), IIIB: 56.4% (53), and IVA: 10.6% (10). Mean high-risk clinical target volume was 75.72 cc, and mean cumulative equivalent of 2 Gy per fraction for high-risk clinical target volume was 81 Gy. The median followup was 35.5 months. Overall 3- and 5-year local control, disease-free survival (DFS), and overall survival (OS) were 84% and 84%, 69.1% and 62.9%, and 80.9% and 71.5%, respectively. Local control (90.4% vs. 76.2%; p = 0.048) and DFS (78.8% vs. 57.1%; p = 0.04) were significantly better in the patients of IC-ISBT arm. IC-ISBT (hazard ratio: 0.763; 95% confidence interval 0.217, 1.38; p = 0.046) and D90 dose >85 Gy (hazard ratio: 0.957; 95% confidence interval 0.927, 1.07; p = 0.037) were predictors of better DFS on univariate analysis. Overall survival was not affected significantly by any of the factors. Grade 3 and 4 late complications were recorded in 3.2% (3) of patients and were similar in both arms (p = 0.86). However, the mean rectum 2 cc dose was significantly lower in the IC-ISBT arm (p = 0.038). CONCLUSIONS: Combined IC-ISBT is a safe and effective approach to treat ICBT unsuitable cases. It integrates the benefits of ICBT to the adaptability of ISBT around various targets and should be practiced whenever feasible to provide superior outcomes in locally advanced cervical cancer.

Change of telomerase activity in peripheral blood of patients with head and neck squamous cell carcinoma pre and post curative treatment.

BACKGROUND: There is no clinically applicable tumor marker for head and neck cancers. Telomerase is detected in approximately 90% of all malignant tumors, it may predict poor or favorable outcomes, thus being both a highly attractive biomarker and a target for the development of molecular-based cancer diagnostics, prognostics, and therapeutics. AIM: Primary aim was to detect a change of telomerase activity before and after curative treatment. MATERIALS AND METHODS: Patients with biopsy proven head and neck squamous cell carcinoma, stage I-IVB treated with a curative intent, performance status 0-2 and malignancy at one primary site were included in the study. Telomerase levels were tested in tissue biopsy. Plasma telomerase levels were tested at baseline, 5 days and at 3 months after treatment using ELISA. RESULTS: Raised plasma telomerase activity was seen in all the patients with cancer at baseline. The mean plasma telomerase level at baseline was 861.4522 ng/ml, at 5 days after completion of curative treatment was 928.92 ng/ml and at 3 months of follow up was 898.87 ng/ml. The mean tissue biopsy telomerase level was 19768.53 ng/mg. There was a significant increase in baseline telomerase levels in cancer patients compared to normals (volunteers) (t = -3.52, p = 0.001).There was a significant increase in plasma levels of telomerase at 3 months compared to baseline values (z = -1.98, p = 0.04). The increase in telomerase level did not correlate with the response of the treatment. CONCLUSION: In patients with head and neck squamous cell carcinomas treated with a curative intent, the change in levels of telomerase correlates neither with the disease status nor with prognostic factors.

Cross-sectional study of psychiatric morbidity in patients with melasma.

CONTEXT: Patients with dermatological problems have higher prevalence of psychiatric illnesses than the general population. Melasma, hyperpigmentation of skin over sun-exposed areas, has bidirectional cause-effect relationship with depression and stress through psycho-neuro-endocrine pathways. AIMS: The aim of this study is to study the psychiatric morbidity and perceived stress in patients with melasma and statistically compare objective study parameters with those without melasma. SETTINGS AND DESIGN: This cross-sectional descriptive study was carried out in Tertiary hospital in urban setting, jointly by psychiatrist and dermatologist. METHODS AND MATERIALS: The study involved 50 consecutive patients with melasma and 30 relatives of patients coming to dermatology clinic not having any skin disorder. Cases were assessed by psychiatrist as per the International Classification of Diseases-10 Diagnostic Criteria for Research, Cohen's 4 item perceived stress scale, Disability Assessment Scale 2.0 by WHO and Hospital Anxiety Depression Scale (HADS) and Dermatologist calculated melasma area severity index score (MASI). RESULTS: Majority patients were females (88%) in the reproductive age group. The most common psychiatric morbidity seen in 42% cases was major depressive disorder. Adjustment disorder (26%) was the second most common diagnosis. Nonparametric analysis using Mann-Whitney U test revealed significantly more perceived stress (P = 0.001), more disability (P = 0.000) and anxiety-depression on HADS (P = 0.0 16) in cases than in their relatives. LIMITATIONS: This was a hospital-based study and thus melasma patients in the community are not represented. Small sample size, less number of controls, lack of structured diagnostic interview are other limitations of this study. CONCLUSIONS: There is high psychiatric comorbidity (76%) of depressive and stress disorders, higher functional disability and perceived stress in patients with melasma compared to controls.