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Background and Purpose: Although there is a strong biological rationale to electively treat the pelvic nodes during bladder preservation, its clinical benefit is uncertain. This may be explained by the incidental dose received by the nodal regions when treating the bladder alone. This study was conducted to investigate the doses received by the different pelvic nodal regions when the bladder alone is treated by standard conformal radiotherapy. Methods and Materials: The computed tomography data sets of 20 patients with node-negative muscle-invasive bladder cancer treated in a bladder preservation protocol were studied. Patients were originally treated with conformal radiotherapy to the bladder alone. Replanning was done with additional delineation of the pelvic nodal regions namely common iliac (upper and lower), presacral, internal iliac, obturator, and external iliac. Dose volume parameters such as Dmean, Dmax, D100%, D66%, D33%, V40, and V50 to each of the nodal regions were estimated for all patients. Results: The obturator nodes received the highest dose among all nodal regions. The mean dose received by obturator, external iliac, and internal iliac regions was 59, 45, and 36 Gy, respectively. The dose received by these 3 regions in the full bladder state was 63, 52, and 47 Gy, respectively. The dose received by all other pelvic nodal regions was low and not clinically relevant. Conclusion: The incidental dose received by obturator and external iliac nodes is clinically significant in bladder-only radiation, possibly enough to influence micrometastatic disease. This may be a reason for the lack of clear benefit seen with nodal irradiation in bladder cancer. Advances in Knowledge: This study highlights that the incidental dose received by obturator and external iliac nodes is clinically significant in bladder-only radiation. The obturator nodes received the highest dose among all nodal regions with mean dose of 59 Gy.

Introduction: Distress is commonly seen in head and neck cancer patients undergoing radiotherapy. Causal factors of distress are multifactorial; which encompasses physical, psychological, spiritual, and existential factors with complex interrelationship among the factors. Materials and Methods: Thirty patients undergoing head and neck radiotherapy were included in the study. Patients were screened for pain scores, distress scores, physical and psychological symptoms, and spiritual and emotional distress. Results: Significant increasing trend seen for pain score, distress score, and total number of symptoms during 2 nd week, 4 th week, and on completion of radiotherapy treatment (all P′s < 0.001) compared to pretreatment. Those who had chemotherapy (CT) along with radiation had significantly greater pain score (t = 5.54, P = 0.03) and distress score (t = 3.9, P = 0.05) at 2 weeks into radiotherapy compared to those who did not receive CT. There was significantly higher grade of skin toxicity in those with spiritual distress (Somers′ d = 0.36, P = 0.02) and higher grade of mucositis in those with existential distress (d = 0.34, P = 0.02) at 4 weeks into radiotherapy. Conclusion: Positive correlation between distress score and pain score and occurrence of physical symptoms. Increasing trend seen for pain score, distress score, and total number of symptoms during 2 nd week, 4 th week, and completion of radiotherapy treatment compared to pretreatment. Increase in distress score in those with existential and spiritual distress.

Purpose To estimate the difference in income generated if all women presenting in our institute over a 5-year period were treated with MRI-based image-guided brachytherapy (MR-IGBT) instead of conventional radiograph–based brachytherapy (CR-BT). Methods and Materials Outcome data from 463 patients (94 treated with MR-IGBT) treated in our institute was used to simulate cumulative women-days of work and cumulative income over 5 years for 5526 patients expected to be treated in this period. The average daily income for a woman was derived from the National Sample Survey Organization (NSSO) survey data. Outcomes from both unmatched and propensity score-matched data sets were simulated. Results The cumulative income in 5 years ranged between Rs 101–168 million if all patients presenting at our institute underwent MR-IGBT. The simulated excess income ranged from Rs 4–45 million after 5 years, which represented 6–66% of the expenditure incurred for acquiring the required equipment and manpower for practicing exclusive MR-IGBT. Conclusions Using outcome data from a prospective cohort of patients treated with MR-IGBT in our institute, we demonstrated that significant economic gains may be realized if MR-IGBT was used instead of CR-BT.

Objectives: Pelvic lymph nodal regions receive an incidental dose from conformal treatment of the prostate. This study was conducted to investigate the doses received by the different pelvic nodal regions with varying techniques used for prostate radiotherapy. Methods and Materials: Twenty patients of high-risk node-negative prostate cancer treated with intensity-modulated radiotherapy to the prostate alone were studied. Replanning was done for intensity-modulated radiotherapy, 3-dimensional conformal treatment, and 2-dimensional conventional radiotherapy with additional delineation of the pelvic nodal regions, namely, common iliac (upper and lower), presacral, internal iliac, obturator, and external iliac. Dose–volume parameters such as Dmean, D100%, D66%, D33%, V40, and V50 to each of the nodal regions were estimated for all patients. Results: The obturator nodes received the highest dose among all nodal regions. The mean dose received by obturator nodal region was 44, 29, and 22 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The mean dose was significantly higher when compared between 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment ( P < .001), 2-dimensional conventional radiotherapy and intensity-modulated radiotherapy ( P < .001), and 3-dimensional conformal treatment and intensity-modulated radiotherapy ( P < .001). The D33% of the obturator region was 64, 39, and 37 Gy from 2-dimensional conventional radiotherapy, 3-dimensional conformal treatment, and intensity-modulated radiotherapy, respectively. The dose received by all other pelvic nodal regions was low and not clinically relevant. Conclusion: The incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques as used in the trials studying elective pelvic nodal irradiation. However, with intensity-modulated radiotherapy, this dose is lower, making elective pelvic irradiation more relevant. Advances in Knowledge: This study highlights that incidental dose received by obturator regions is significant especially with 2-dimensional conventional radiotherapy and 3-dimensional conformal treatment techniques.

To evaluate the effect of the menstrual cycle in HIV-positive women on plasma and genital cytokine levels, interrelationships between vaginal and plasma cytokines, CD4 and CD8 T cell fluctuations, and genital and plasma viral loads.Plasma and cervicovaginal lavage specimens were collected from 55 HIV-positive women with CD4 cell counts350 cells/microl during phases of the menstrual cycle. Samples were assayed for IL-1beta, IL-6, IL-4, IL-8, IL-10, TGFbeta, TNFalpha, INFgamma, MIP1alpha, MIP1beta, RANTES, and TNFR-II using enzyme-linked immunosorbent assays. CD4 and CD8 T cell expression was evaluated by flow cytometry. Repeated measures regression models were used to assess the effect of the menstrual cycle on cytokines and viral load. Multivariate repeated regression models were used to assess the correlation among selected cytokines and between selected cytokines and HIV viral load.Vaginal IL-1beta, IL-4, IL-6, IL-8, IL-10, MIP1beta, RANTES, TGFbeta, and TNFR-II were significantly elevated during menses but were not altered during other phases. Plasma cytokine levels were not altered during the menstrual cycle. A positive Candida culture increased vaginal IL-8 during menses, whereas vaginal discharge was associated with a reduction in vaginal IL-4, IL-10, and RANTES. CD4 and CD8 cell numbers did not vary with the menstrual cycle. Vaginal cytokine levels correlated only with vaginal viral load, in a sampling method-dependent manner.We provide evidence of elevated vaginal cytokine levels during menses, which appear to regulate vaginal and not plasma HIV shedding, suggesting that a menstrual cycle pattern exists for cytokine production in HIV-positive women impacting vaginal shedding of HIV.

OBJECTIVE To assess the variation in HIV-1 over the menstrual cycle, including RNA levels in the female genital tract, plasma HIV-1-RNA levels, CD4 cell counts, and culturable virus. DESIGN A prospective analysis of 55 HIV-1-infected women. METHODS Blood and genital tract specimens were collected weekly over 8 weeks, spanning two complete menstrual cycles. Applying repeated-measures models that used menses as the reference level, the variation in viral RNA levels was compared in endocervical canal fluid and cells (collected by Sno-strips and cytobrush, respectively) and ectocervicovaginal lavage (CVL) fluid. Repeated-measures models were also used to assess the variation in plasma CD4 cell counts and viral load. RESULTS Shedding patterns differed among the three sampling methods, independent of genital tract co-infections. Genital tract HIV-1-RNA levels from CVL fluid and endocervical canal cytobrush specimens were highest during menses and lowest immediately thereafter (P = 0.001 and P = 0.04). The HIV-1-RNA level in endocervical canal fluid was highest in the week preceding menses (P = 0.003). The menstrual cycle had no effect on blood levels of RNA (P = 0.62), culturable virus (P = 0.34), or CD4 cell counts (P = 0.55). HIV-1-RNA levels were higher in endocervical canal fluid than in peripheral blood plasma during the late luteal phase (P = 0.03). CONCLUSION HIV-1-RNA levels vary with the menstrual cycle in the female genital tract but not the blood compartment. HIV-1-RNA levels are higher in endocervical canal fluid than in blood plasma. These findings may have important implications for sex-specific pathogenesis, heterosexual transmission, and contraceptive hormone interventions in HIV-1-infected women.

To understand the impact of the menstrual cycle on immunologic parameters, we measured the level of cytokines and chemokines from plasma, cervicovaginal lavage (CVL), and saliva samples of 6 premenopausal women during the follicular and luteal phases of the ovulatory cycle. We demonstrate that the level of plasma interleukin-8 (IL-8) was 4-fold higher during the follicular phase than the luteal phase (p = 0.004), whereas plasma IL-1beta, IL-4, IL-6, IL-10, interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), and TNF receptor II (TNFR II) were not altered during the ovulatory cycle. In the vaginal compartment, as measured from CVL samples, the levels of IL-6 and IL-1beta were both 5-fold higher in the follicular than the luteal phase (p = 0.0002 and 0.03, respectively). Salivary cytokine and chemokine samples were similar when measured during the luteal and the follicular phases. Additional analysis of lymphocyte subsets for phenotypic and functional markers indicated that they were not influenced by the ovulatory cycle. Collectively, these data suggest that IL-6, IL-8, and IL-1beta are differentially regulated during the ovulatory cycle.

BACKGROUND: Outcomes and survival of truly unresectable locally advanced pancreatic cancers (LAPC) is often reported along with borderline resectable pancreatic cancers especially from a real world cohort. METHODS: The audit of LAPC patients, diagnosed based on the NCCN criteria between February 2013 and January 2016 was used to identify patients starting and continuing treatment in our institution. Practice patterns, outcomes and prognostic factors for overall survival were evaluated. RESULTS: Of the 83 patients, 52 were available for inclusion in the analysis. Median age was 56 years (range 30- 77), with males constituting 75% of patients. Baseline comorbidities seen were diabetes mellitus, hypertension and cardiac dysfunction in 46.1%, 69.1% and 52% of patients respectively. 84.6% of patients had arterial vascular involvement as criteria for unresectable LAPC. 50% of patients received chemotherapy only, while the remainder received chemotherapy and concurrent chemoradiation. One patient was able to undergo curative R0 resection. FOLFIRINOX was the most commonly used chemotherapy regimen (53.8%). With a median follow up of 15.9 months, median progression free survival (mPFS) was 7.26 months (95% CI: 5.75-8.76) and median OS was 11.8 months (95% CI: 9.96 – 13.61). None of the potential prognostic factors evaluated, i.e., age, gender, nodal status, pre-treatment CA 19.9 levels, showed correlation with OS. CONCLUSION: This analysis shows outcomes in unresectable LAPC comparable to existing literature. Surgery in unresectable LAPC patients is less common than seen in previously published studies, more likely due to this cohort being truly 'unresectable' in terms of major arterial involvement.

The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antagonists with markedly improved biological and pharmacokinetic properties, which are suitable pharmacological tools to probe the in vivo effects of CXCR2 antagonism combined with the associated CCR2 activity.

e19509 Background: To evaluate the prognostic factors and treatment outcome of Indian patients with primary Diffuse Large B-Cell Lymphoma (DLBCL) of the stomach treated at a single institution. Met...

The short-term detection and variability of human immunodeficiency virus type 1 (HIV-1) RNA level was assessed in the blood plasma and genital tracts of 55 HIV-1-infected women. Specimens were collected weekly for 8 weeks from the endocervical canal with wicks and cytobrushes and from the ectocervix and vagina with cervicovaginal lavage. In all, 48 women (87.3%) had detectable genital tract HIV-1 RNA at > or =1 collection times. HIV-1 RNA levels varied least in specimens from endocervical canal wick and most in cervicovaginal lavage samples. The within-subject variation for genital-tract virus level was greater than that for blood. Overall, the odds for viral RNA detection in the genital tract approximately tripled for each 10-fold increase in plasma viral RNA concentration (P

Per the Patient Self-Determination Act of 1991, hospitals are required to ascertain whether patients have an advance directive (AD). At this point, factors prompting patients to issue ADs have not been studied. The purpose of this study was to describe patients' understanding of ADs as well as the process patients used to arrive at their decisions to implement an AD. A stratified random sample of 26 patients from two intensive care units, one general medical unit, one general cardiac unit, and one acquired immunodeficiency unit were selected for participation. Patients were asked a series of open-ended questions to determine their knowledge and understanding of ADs. The constant comparative method was used to review the transcripts. It was found that only 31 per cent of patients had issued an AD, and 20% had learned of ADs for the first time during their hospitalization. Response analysis showed four phases of AD decision making: evaluation of illness, establishment of priorities, consideration of implications of the directives, and selection or rejection of directives. In conclusion, patients continue to have limited understanding of ADs and their implications. Continued investigation will elucidate the best strategies to educate patients about this topic.

Although breast cancer cannot be prevented at this time, early detection is the single most important factor in recovery. Early detection is largely dependent on discovery of the breast cancer by women through self breast examinations. This study indicates that health professionals either neglect to teach breast self‐exam (BSE) or fail to document teaching it in the patient's record. One hundred eight records of hospitalized clients who had identified risk for breast cancer were reviewed for documentation of teaching of BSE by the health professional. Even though all clients had multiple risk factors, no documentation of teaching BSE was present. These findings indicate a need for some structure in the health care system to assure that health professionals are fulfilling their obligations to teach BSE and to document it in the patient's records. Including it as part of nursing history, a standard nursing care plan, or as a part of audit criteria would assure more consistency in the teaching of BSE.