A Monte Carlo simulation-based decision support system for radiation oncologists in the treatment of glioblastoma multiforme.

In the present research, we have developed a model-based crisp logic function statistical classifier decision support system supplemented with treatment planning systems for radiation oncologists in the treatment of glioblastoma multiforme (GBM). This system is based on Monte Carlo radiation transport simulation and it recreates visualization of treatment environments on mathematical anthropomorphic brain (MAB) phantoms. Energy deposition within tumour tissue and normal tissues are graded by quality audit factors which ensure planned dose delivery to tumour site thereby minimising damages to healthy tissues. The proposed novel methodology predicts tumour growth response to radiation therapy from a patient-specific medicine quality audit perspective. Validation of the study was achieved by recreating thirty-eight patient-specific mathematical anthropomorphic brain phantoms of treatment environments by taking into consideration density variation and composition of brain tissues. Dose computations accomplished through water phantom, tissue-equivalent head phantoms are neither cost-effective, nor patient-specific customized and is often less accurate. The above-highlighted drawbacks can be overcome by using open-source Electron Gamma Shower (EGSnrc) software and clinical case reports for MAB phantom synthesis which would result in accurate dosimetry with due consideration to the time factors. Considerable dose deviations occur at the tumour site for environments with intraventricular glioblastoma, haematoma, abscess, trapped air and cranial flaps leading to quality factors with a lower logic value of 0. Logic value of 1 depicts higher dose deposition within healthy tissues and also leptomeninges for majority of the environments which results in radiation-induced laceration.

Accelerated hypofractionated chemoradiation for locally advanced head and neck cancer during COVID 19 pandemic: A tertiary care experience.

PURPOSE: To assess the role of Accelerated Hypofractionated Chemoradiation for Locally Advanced Head & Neck squamous cell cancer (HNSCC) during COVID 19 pandemic. MATERIALS AND METHODS: Previously untreated 20 patients with locally advanced HNSCC (Oral cavity/oropharynx/larynx/hypopharynx) were treated with definitive hypofractionated radiotherapy of 60Gy in 25 fractions with concurrent cisplatin @35 mg/m2 once weekly for 5 weeks from March 2020 to November 2021. The patients were treated on 6MV LINAC with Volumetric modulated arc therapy (VMAT) by the Sequential boost technique and concurrent chemotherapy @35 mg/m2. All the patients received 48Gy in 20 fractions to low-risk volume (CTV LR) in Phase I followed by 12Gy in 5 fractions boost to High-risk volume (CTV HR) in Phase II. The organs at risk (OARs) were contoured and appropriate constraints were given considering the hypofractionated regimen. RESULTS: Out of 20 patients, most of the patients were Stage IV (15;75%) & stage III 20%, out of which (55%) 11 were of the oral cavity, (40%) 8 were of the oropharynx, and (5%) 1 of larynx. All patients were treated with 60Gy/25#/5 weeks with the majority of the patients (17;85%) completing their treatment in less than 45 days. The Median follow-up was of 214 days. The locoregional control at 6 Months was 55%. Maximum acute toxicity was grade 3 mucositis which was observed in 18 (90%) patients. Ryle's tube feeding was needed in 11 (55%) patient. Out of 20 patients, 5 patients did not receive concurrent chemotherapy, and 8 (40%) patients received all 5 cycles of chemotherapy. 7, 35% of the patients could not complete all 5 cycles of concurrent chemotherapy due to grade 3 mucositis. CONCLUSION: During a pandemic crisis with limited manpower & technical resources accelerated hypofractionated radiotherapy with concurrent chemotherapy can be considered a feasible therapeutic option for HNSCC which can significantly reduce the overall Treatment Time (OTT) with comparable local control and manageable toxicities.

Dose at posterior-inferior border of symphysis point: A predictor for vaginal stricture in cervical cancer.

PURPOSE: To study the effect of various dose-volume parameters on the severity of vaginal stricture (VS) and the correlation of the latter with the posterior-inferior border of symphysis (PIBS) points in locally advanced cervical cancer patients treated with concurrent chemoradiation and brachytherapy. METHODS AND MATERIALS: A prospective study was done on 45 histologically proven locally advanced cervical cancer patients between January 2020 and March 2021. All of them were treated with concurrent chemoradiation with 6 MV photon linear accelerator to a dose of 45 Gy/25 fractions in 5 weeks. Twenty-three patients were treated with intracavitary brachytherapy with a dose of 7 Gy/fraction/week for three fractions. Twenty-two patients were treated with interstitial brachytherapy, with 6 Gy/fraction for four fractions, each fraction 6 h apart. Grading of VS was done as per Common Terminology Criteria for Adverse Events version 5. RESULTS: The median followup was 21.5 months. About 37.8% of patients had VS with a median duration of 8.0 months (4.0-12 months). About 22.2% had Grade 1, 6.7% had Grade 2, and 8.9% had Grade 3 toxicity. Doses at PIBS and PIBS-2 points had no correlation with vaginal toxicity, however, the dose at PIBS+2 was significantly associated with VS (p = 0.004). The treated length of the vagina at the time of brachytherapy (p = 0.001), initial tumor volume (p = 0.009), and vaginal involvement after completion of external beam radiotherapy (EBRT) (p = 0.01) were also statistically significant with the development of VS of Grade 2 or more. CONCLUSIONS: Dose at PIBS + 2, treated length of the vagina with brachytherapy, initial tumor volume, and post-EBRT vaginal involvement are strong predictors for the severity of VS.

Effect of Laparoscopic Sleeve Gastrectomy on Quality of Life.

PURPOSE: The clinical benefits of bariatric surgery are well-established, but the impact of bariatric surgery on psychosocial outcomes such as health-related quality of life (HRQL) is less clear. The aim of this study is to assess the Quality of life (QOL) as a whole and in separate domains in post-bariatric surgery patients. METHODOLOGY: A single unit cross-sectional analysis of a prospective study is done on QOL in 51 patients undergoing laparoscopic sleeve gastrectomy at tertiary hospital. QOL was assessed by WHOQOL-BREF (World Health Organisation Quality of Life questionnaire -Brief version) questionnaire and Global Quality of Life Scale in each patient. Scores were calculated on a 0-100 scale and results compared. RESULTS: The median scores given by patients before surgery were 14, 21, 42, 40 and 12.5 for each of the parameters physical, psychological, social, environmental and overall well-being respectively. The median scores for after surgery were 86, 87, 91, 88 and 87.5 respectively. The difference was significant (p value 0.001). Global QOL after surgery, calculated year wise, showed QOL scores of 90, 100, 95 and 80 in patients with 1 year, 2 years, 3 years and 4 years of follow-up without any significant difference (p value 0.502). CONCLUSION: Through this study, we emphasize the need for the selection of a standardised scale by international organisations to compare the different studies. By proving the significant differences in the QOL of patients who underwent LSG [laparoscopic sleeve gastrectomy], we suggest to consider the Quality of Life as one of the criteria to consider a patient for bariatric surgery.

A prospective randomized comparison of simultaneous integrated boost with sequential boost intensity-modulated radiotherapy in locally advanced head and neck cancer.

Purpose: A comparison of simultaneous integrated boost (SIB) with sequential boost (SEQ) using intensity-modulated radiotherapy along with concurrent cisplatin in locally advanced head and neck cancer (HNC) was made with regard to their survival outcomes and toxicity profile. Materials and Methods: A total of 34 patients were enrolled between October 2016 and March 2019. They were randomized into two arms, SIB and SEQB. All patients were treated with 6 MV photon beam on Linear Accelerator with weekly concurrent cisplatin at 35 mg/m2. Overall survival (OS) and disease-free survival (DFS) were the primary end points and acute and late toxicities were the secondary end points. Results: The median follow-up period was 40.6 and 37.3 months for SIB and SEQB, respectively. At the end of 5 years, the median OS was 40.6 and 37.3 months (P = 0.947) and the median DFS was 35.1 and 37.3 months in the SIB and SEQB arms, respectively (P = 0.991). Complete response at 3 months was 64.7% and 76.5% and partial response was 23.5% and 17.6%, whereas progressive disease was 11.8% and 5.9% in SIB and SEQB arms, respectively. Acute dermatitis, mucositis, dysphagia, and salivary gland toxicities were higher in the SIB arm compared to the SEQB arm. Conclusion: SIB and SEQ arms were comparable in terms of OS and DFS. However, the acute toxicities were higher in the SIB arm, although the difference was not significant, compared to the SEQB arm.

A mathematical model to predict the different isodose volumes using TRAK value in HDR intracavitary brachytherapy for revised Manchester and ICRU-89 based Point A plans using computer tomography images.

Purpose: To find out the simple relationship between Total Reference Air Kerma (TRAK) and various isodose volumes. Calculated isodose volumes were compared with experimental data for revised Manchester and International Commission on Radiation Units and measurements (ICRU)-89 Point A-based treatment plans. The accuracy of the formula was compared with the results of other relationships available in the literature. Materials and Methods: Dosimetric data from 62 intracavitary brachytherapy (ICBT) treatment plans of 31 patients with cervical cancer were studied. Each patient had treatment plans normalized to revised Manchester and ICRU-89 Points A (Aflange and Aicru89). For each treatment plan, TRAK values, V350, V700, V1050, and V1400 were obtained. The modeling curve was plotted between Isodose volume (Vd) and the ratio of d/TRAK obtained from Aflange plans to get a mathematical relation. The results of this formula were compared with the experimental data and outcomes of other formulas available in the literature. A paired-sample t-test was performed to assess the statistical significance. Results: In the case of revised Manchester-based Aflange normalization plans, the mean isodose volume of V350, V700, V1050, and V1400 were 285.98 ± 32.3 cm3, 101.96 ± 10.63 cm3, 52.71 ± 4.72 cm3, and 31.44 ± 2.33 cm3 respectively. Likewise, for ICRU-89 based Aicru89 normalization plans, the mean isodose volumes of V350, V700, V1050, and V1400 were 304.11 ± 26.17 cm3, 108.88 ± 8.29 cm3, 56.62 ± 3.69 cm3 and 34 ± 2.23 cm3 respectively. The mean difference was significant. The Mathematical relationship developed was [INLINE:1]. No correlation was found between TRAK and D0.1cm3,D2cm3 for organs at risk. Conclusions: The developed formula calculated isodose volumes within the accuracy of ± 3% in ICBT plans.

Feasibility of using polytetrafluoroethylene flexible implant tube for interstitial brachytherapy patients.

PURPOSE: To design the different Polytetrafluoroethylene (PTFE) based flexible implant tubes using an in-house developed device and to evaluate them for High dose rate (HDR) interstitial brachytherapy using computer tomography images. METHODS AND MATERIALS: PTFE hollow tube having a 2 mm (6 French) outer diameter (OD) and 1.4 mm inner diameter (ID) was used to design in-house single and/or double leader flexible catheters for interstitial brachytherapy implant. An in-house Plastic Wire Drawing Plate (PWDP) machine was developed. Customization of PTFE hollow flexible implant tube (FIT) was done through PWDP. Different percentages of BaSO4 (5%, 10%, & 15%) were added to Nylon 6 to make radiopaque button. Various quality assurance tests were performed with the PTFE tubes implanted in the brinjal (phantom) before using them on the patients. That is, coupling of brachytherapy machine transfer tube with flexible PTFE Tubes, CT scan artifacts, tube kinks, breast template, and free-hand compatibility. RESULTS: With the help of the PWDP machine, plastic wires of different lengths were made for single leader and double leader tubes. The different plastic leader ends of 1 cm to 50 cm lengths having 1 mm diameter were created. The radiopaque button of Nylon 6 in circular shape having 1 cm diameter and 0.5 cm thick was created. Developed radiopaque buttons were visible on CT scan images as well as on radiograph images. CONCLUSIONS: PTFE tubes of the desired length can be made depending upon the size of the brachytherapy implant and are inexpensive than commercially available flexible implant tubes.

Influence of adjuvant therapy on pattern of failure and survival in curatively resected gallbladder carcinoma.

PURPOSE: The study was done to evaluate the role of adjuvant therapy in curatively resected Stage II and III gallbladder carcinoma (GBC). MATERIALS AND METHODS: This was a retrospective analysis of patients of GBC registered between 2008 and 2017 in outpatient department of a tertiary cancer hospital in India. Patients who had any of the following adjuvant treatment after radical surgery: (a) external beam radiotherapy (RT) alone, (b) chemotherapy (CT) alone, and (c) RT with CT (CRT) were considered for the study. RESULTS: A total of fifty patients could meet the selection criteria. It was seen that seven patients were treated with RT, 20 with CT, and 23 with CRT. Median follow-up for patients who were alive was 26.7 months. Nineteen patients had locoregional failure while eight had distant failure. Patients treated with CRT had a significantly better mean overall survival compared to those treated with RT or CT (44.0 months, 12.5 months, and 15.1 months, respectively; P = 0.003). Similarly, mean disease-free survival was superior in CRT arm compared to RT and CT arms (43.6 months, 9.6 months, and 12.4 months, respectively; P = 0.002). CONCLUSIONS: Adjuvant CRT had better survival outcome compared to patients treated with either RT or CT with Stage II and III disease after curative cholecystectomy.

Dose optimization comparison study of inverse planning simulated annealing [IPSA] and hybrid inverse planning optimization [HIPO] in interstitial brachytherapy of head and neck cancer.

PURPOSE: This study was a retrospective dose optimization comparison of two commercially available inverse planning algorithms, the inverse planning simulated annealing (IPSA) and hybrid inverse planning optimization (HIPO) for head and neck cancer interstitial brachytherapy. MATERIALS AND METHODS: Seven patients with head and neck cancer were selected (4 with tongue cancer, 2 with buccal mucosa cancer and 1 with carcinoma lip) who were previously treated with interstitial brachytherapy using a flexible nylon tube catheter and graphical optimization/geometric optimization technique. All seven patients were retrospectively re-planned using both IPSA as well as HIPO algorithms available in the Oncentra Brachytherapy Treatment Planning System (TPS) version V4.5.3.30. The dosimetric parameters [PTV-V100, V150, V200, D90; mandible-D2cc, parotid-D2cc, conformity index (CI), dose homogeneity index (HI), overdose volume index (ODI)] were chosen for evaluation in compliance with the objective function and organ at risk dose constraints. RESULTS: Using the paired sample T test in chosen parameters (PTV-V100, V150, V200, D90; mandible-D2cc, CI, HI, ODI both the inverse planning algorithms), it was found that IPSA and HIPO were comparable. CONCLUSIONS: Even though both IPSA and HIPO are largely comparable in most of the dosimetric parameters for inverse planning in brachytherapy of head and neck cancers, differences in the algorithms can be exploited to improve certain parameters in specific situations such as D2cc parotid.

An assessment of serum oxidative stress and antioxidant parameters in patients undergoing treatment for cervical cancer.

OBJECTIVES: Oxidative stress and antioxidants are involved in all aspects of cervical cancer. The present study evaluated serum levels of oxidative stress and antioxidant biomarkers in cervical cancer patients and healthy controls. Moreover, the effect of Concurrent chemoradiotherapy (CCRT) on these biomarkers and their association with treatment outcome was investigated. DESIGN: This study included ninety-seven cervical cancer patients and thirty controls. Three oxidative stress parameters (8-hydroxy-2-deoxyguanosine, Protein Carbonyl, and Malondialdehyde) and four antioxidant parameters (Superoxide Dismutase, Catalase, Glutathione Peroxidase, and Total Antioxidant Status) were measured. The analysis was conducted using repeated measures ANOVA for comparing among the phases (before, during, and follow-up) of treatment. The control group was compared using the Dunnet test. Logistic regression analysis was also conducted between oxidative stress and antioxidant parameters to study their association. RESULTS: Significant rises in oxidative damage markers were observed in cervical cancer patients of all stages, compared to controls. There was a further increase in oxidative stress markers during CCRT among complete responders. However, among non-responders, the oxidative stress biomarkers like Protein Carbonyl and Malondialdehyde were unaltered during CCRT. Simultaneously, there was a significant decrease in antioxidant parameters in cervical cancer patients of all stages compared to controls. During CCRT, antioxidant levels continuously depleted among complete responders. Nevertheless, in non-responders, antioxidant parameters like Superoxide Dismutase and Total Antioxidant Status were consistent. The oxidative stress markers and antioxidant parameters normalized among complete responders at six months follow up. While in non-responders, the normalization of these parameters was not observed. CONCLUSION: Our results indicate that increased oxidative stress and diminished antioxidants among patients were associated with carcinoma cervix. Induced oxidative stress and decreased antioxidant parameters during CCRT among the complete responders show the treatment's efficacy. Oxidant-antioxidant profile merits investigation as markers of diagnosis, treatment response, survival, and recurrence in extensive prospective studies.

Diagnostic and prognostic application of Raman spectroscopy in carcinoma cervix: A biomolecular approach.

Blood serum samples from 63 cervical cancer patients and 30 controls were collected at three different phases of the treatment (i.e. before, during, and at follow up). The spectra of serum samples from control as well as patients were classified into different groups using principal component analysis (PCA) and linear discriminant analysis (LDA) based on different phases of treatment using R software. The spectra of blood serum samples have shown the distinct changes and differences compared with each other in the profile of various biochemical parameters. The sensitivity (92.5%) and specificity (85%) were observed maximum between control and cervical cancer patients (before treatment). Between different phases of treatment, the sensitivity and specificity were less but, all accuracies of detection and classification reached above 50%. This method can be considered as a screening method for detection and treatment monitoring.

Evolution of Brachytherapy Applicators for the Treatment of Cervical Cancer.

Brachytherapy applicators have come a long way since Danlos developed early intracavitary applicators to treat cervical cancer patients. Therefore, this review will help in the neoteric designs of intracavitary applicators. A detailed literature survey of the gynecological brachytherapy applicators from the era of preloading to conceptual intensity-modulated brachytherapy applicators has been carried out. Depending on the extent of the disease and patient anatomy, the selection of brachytherapy applicators plays a pivotal role in the treatment of cervical cancer. Furthermore, the selection of the applicators is also based on the imaging modalities to be used for applicator reconstruction and treatment planning. Dose acceleration in the target and reduction in nearby organs at risk can be optimized using an applicator having the capabilities of intensity-modulated brachytherapy. Now, three-dimensional printed applicators are used for patient-specific tailor-made treatment and they are fast replacing the old conventional applicators. Newer advancements in technology have greatly influenced the neoteric designs of intracavitary brachytherapy applicators.

A comparison between revised Manchester Point A and ICRU-89-recommended Point A definition absorbed-dose reporting using CT images in intracavitary brachytherapy for patients with cervical carcinoma.

PURPOSE: This study is a comparison between revised Manchester Point A and International Commission on Radiation Units and measurements (ICRU) 89 report-recommended Point A absorbed-dose reporting in intracavitary brachytherapy for patients with cervical carcinoma. METHODS AND MATERIALS: The retrospective dosimetric study is based on the data of 32 patients with cervical carcinoma treated with high-dose-rate brachytherapy. Patients received 21 Gy in three fractions (7.0 Gy X three fractions) to Point A (Aflange, revised Manchester definition). All the patients were replanned with a new Point A (Aicru89) defined on CT images as per the American Brachytherapy Society/ICRU-89. The data collected were compared with the data obtained from Point A (Aflange). RESULTS: When using the Aflange plan normalization method, the mean dose of 0.1 cc, 1 cc, and 2 cc bladder volumes was 820.79 ± 207.47 cGy, 654.66 ± 152.69 cGy, and 588.91 ± 136.35 cGy, respectively. Likewise, when using the ICRU-89 Point Aicru89 normalization method, the mean dose of 0.1 cc, 1 cc, and 2 cc bladder volumes was 869.30 ± 224.67 cGy, 693.24 ± 166.20 cGy, and 616.61 ± 150.32 cGy, respectively. For the rectum, Point Aflange normalization plans, the mean dose of 0.1 cc, 1 cc, and 2 cc volumes was 589.37 ± 163.26 cGy, 487.51 ± 126.03 cGy, and 442.70 ± 111.43 cGy, respectively. Likewise, using the Aicru89 plan, the mean 0.1 cc, 1 cc, and 2 cc rectum volume was 625.07 ± 171.31 cGy, 517.50 ± 131.05 cGy, 464.94 ± 121.81 cGy, respectively. The statistical mean difference of Total Reference Air Kerma rate, V100 (cc), bladder, rectum and sigmoid, was found significant. CONCLUSIONS: It has been found that the position of revised Manchester (Aflange) and ICRU-89 Point A does not match on CT images/radiograph, which resulted in variation in doses to the tumor, V100 (cc), organ at risk, and Total Reference Air Kerma.

Comparison of two hypofractionated radiotherapy schedules in locally advanced postmastectomy breast cancer patients.

INTRODUCTION: The role of hypofractionated radiotherapy (HFRT) in postmastectomy breast cancer patients is not well established. This study was done to establish the role of two different HFRT schedules in the treatment of chest wall and regional lymph nodes after mastectomy. MATERIALS AND METHODS: Between 2012 and 2016, consecutively registered patients of locally advanced breast cancer patients having undergone mastectomy and adjuvant radiotherapy (RT) at a tertiary cancer center were analyzed. Locoregional recurrence (LRR) was the primary endpoint, whereas overall survival (OS), disease-free survival (DFS), and both acute and late adverse events were secondary endpoints. RESULTS: A total of 34 patients who were treated with 39 Gy in 13 fractions over 2½ weeks and 35 patients who were treated with 40 Gy in 15 fractions over 3 weeks were identified. The median follow-up period was 47 months and 63.5 months in the 39 Gy and 40 Gy arms, respectively. LRR was seen in 11.8% and 8.6% of patients in the 39 Gy and 40 Gy arms, respectively. OS at 4 years was 66% and 71.5% in the 39 Gy and 40 Gy arms, respectively. The mean DFS for 39 Gy and 40 Gy arms was 43.6 months and 66.4 months, respectively (P = 0.822). Acute skin toxicity was similar in the two groups. Arm edema was significantly more in the 40 Gy arm. CONCLUSION: The two HFRT schedules are equivalent to each other in terms of survival outcomes. Arm edema is higher with 40 Gy arm as compared to 39 Gy arm.

Design and development of novel p-aminobenzoic acid derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer's disease.

Based on the quantitative structure-activity relationship (QSAR), some novel p-aminobenzoic acid derivatives as promising cholinesterase enzyme inhibitors were designed, synthesized, characterized and evaluated to enhance learning and memory. The in vitro enzyme kinetic study of the synthesized compounds revealed the type of inhibition on the respective acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vivo studies of the synthesized compounds exhibited significant reversal of cognitive deficits in the animal models of amnesia as compared to standard drug donepezil. Further, the ex vivo studies in the specific brain regions like the hippocampus, hypothalamus, and prefrontal cortex regions also exhibited AChE inhibition comparable to standard donepezil. The in silico molecular docking and dynamics simulations studies of the most potent compound 22 revealed the consensual interactions at the active site pocket of the AChE.

A comparison of six fractions per week chemoradiation versus five fractions per week of conventional chemoradiation in carcinoma cervix: A prospective controlled study.

AIMS: The standard of care for carcinoma cervix stage IB2-IVA is five fractions per week of radiotherapy (RT) with concurrent cisplatin. We compared the standard treatment with six fractions per week of RT with concurrent Cisplatin to see whether the later had improved survival outcomes with comparable toxicities. SETTINGS AND DESIGN: 46 patients of carcinoma cervix with stage IB2-IVAwere randomized into two arms. MATERIALS AND METHODS: Study arm: 46 Gy/23 fractions/26 days, 6 fractions/week with injection CDDP 40 mg/m2 and Control arm: 46 Gy/23 fractions/31 days, 5 fractions/week with injection Cisplatin 40mg/m2. Patients in both the arms received LDR brachytherapy to a dose of 29 Gy at point A. STATISTICAL ANALYSIS USED: The primary end points were disease-free survival (DFS) and overall survival (OS). Compliance to treatment and treatment toxicities were the secondary end points. P value ≤0.05 were considered significant. RESULTS: The study was carried out during June, 2014-April, 2015. Statistical analysis was done in May, 2019. Of 46 patients, 39 patients completed the treatment. The study and control arms had 17 and 22 patients, respectively. Median follow-up period is 45 months (range: 1-54 months). 3-year DFS rates and OS was 69.5% vs. 72.7% (P = 0.73) and 63% vs. 68% (P = 0.45) in study and in control arm, respectively. There was no significant difference in acute and late radiation toxicities between two arms. CONCLUSION: Chemoradiotherapy with six fractions per week seems feasible and equally efficacious in terms of survival outcomes and toxicity profile. Further prospective randomized controlled study is required to prove the merit of altered fractionation with concurrent cisplatin.

Radiation dosimetry and repair kinetics of DNA damage foci in mouse pachytene spermatocyte and round spermatid stages.

Accurate quantification of DNA double strand breaks (DSB) in testicular germ cells is difficult because of cellular heterogeneity and the presence of endogenous γH2AX. Here, we used confocal microscopy to quantify DNA damage and repair kinetics following γ-irradiation (0.5-4 Gy) in three major mouse male germ cell stages, early and late pachytene spermatocytes and round spermatids (RSs), following a defined post irradiation time course. Dose-response curves showing linear best fit validated γH2AX focus as a rapid biodosimetric tool in these substages in response to whole body in vivo exposure. Stage specific foci yield/dose and repair kinetics demonstrated differential radiosensitivity and repair efficiency: early pachytenes (EP) repaired most rapidly and completely followed by late pachytene (LP) and RSs. Repair kinetics for all three stages followed 'exponential decay' in response to each radiation dose. In pachytenes immediate colocalisation of γH2AX and 53BP1, which participates in non-homologous end-joining repair pathway, was followed by dissociation from the major focal area of γH2AX by 4 h demonstrating ongoing DSB repair. These results confirm the differential radiosensitivity and repair kinetics of DSBs in male germ cells at different stages. Taken together, our results provide a simple and accurate method for assessing DNA damage and repair kinetics during spermatogenesis.

Short Bowel Syndrome: An Uncommon Clinical Entity and a Therapeutic Challenge-Our Experience and Review of Literature.

Short bowel syndrome (SBS), one of the commonest types of intestinal failure, usually secondary to extensive bowel resection, traditionally has been associated with a high mortality rate and hence a big challenge for the treating surgeons. It requires comprehensive clinical care to minimise the morbidities and mortality associated with the condition. We report a retrospective review of a series of seven patients with SBS, who presented at our surgical emergency within a period of 1 year and their outcome so as to encourage others in managing such a challenge with more positive mindsets. A retrospective analysis of seven patients with SBS admitted from January 2014 to January 2015 with a follow-up of 1 year has been done in terms of their demographic characteristics, underlying pathology and clinical outcome. A rising incidence of SBS in the younger age group (71.4%) has been observed in this analysis. Majority of patients (57.1%) had mesenteric ischemia as the underlying cause followed by each case of small bowel volvulus, internal herniation and blunt trauma abdomen. A discharge rate of 71.4% and mortality rate of 28.5% were observed. With this analysis, we believe that SBS is no more an uncommon condition. A structured clinical approach, timely surgical intervention and multidisciplinary postoperative management are essential for managing such frail patients to achieve best possible results. This will encourage others in managing such a critically challenged condition with a more positive approach and thus beneficial for both the patients and the treating surgeon.