Anti-Androgen Therapy Overcomes the Time Delay in Initiation of Salvage Radiation Therapy and Rescues the Oncological Outcomes in Men with Recurrent Prostate Cancer After Radical Prostatectomy: A Post Hoc Analysis of the RTOG-9601 Trial Data.

BACKGROUND: It is unknown whether the addition of anti-androgen therapy (AAT) to late salvage radiation therapy (sRT) can lead to oncological outcomes equivalent to that of early sRT in men with recurrent prostate cancer (CaP) after surgery. METHODS: Data on 670 men who participated in the Radiation Therapy Oncology Group (RTOG)-9601 trial and who experienced biochemical recurrence were extracted using the National Clinical Trials Network (NCTN) data archive platform. Patients were stratified into four treatment groups: early sRT (pre-sRT prostate-specific antigen [PSA] < 0.7 ng/mL) and late sRT (pre-sRT PSA ≥ 0.7 ng/mL) with/without concomitant AAT, based on cut-offs reported in the original trial. Time-varying Cox proportional hazards and Fine-Gray competing-risk regression analyses assessed the adjusted hazards of overall mortality, CaP-specific mortality, and metastasis among the four treatment groups. RESULTS: At 15-years (median follow-up of 14.7 years), for patients treated with early sRT, early sRT with AAT, late sRT, and late sRT with AAT, the overall mortality, CaP-specific mortality, and metastasis rates were 22.9, 22.8, 40.1, and 22.9% (log-rank p = 0.0039), 12.1, 3.9, 22.7, and 8.0% (Gray's p = 0.0004), and 18.8, 14.6, 35.9, and 19.5% (Gray's p = 0.0004), respectively. Time-varying multivariable adjusted analysis demonstrated increased hazards of overall mortality in patients receiving delayed sRT versus early sRT (hazards ratio [HR] 1.49, 95% confidence interval [CI] 1.02-2.17); however, no difference remained after the addition of concomitant AAT to late sRT (HR 0.85, 95% CI 0.55-1.32, referent early sRT). Likewise, the hazards of cancer-specific mortality and metastatic progression were worse for late sRT when compared with early sRT, but were no different after the addition of AAT to late sRT. CONCLUSIONS: Poorer outcomes associated with late sRT in men with recurrent CaP may be rescued by delivery of concomitant AAT.

Sexually transmitted infections among incarcerated women: findings from a decade of screening in a Los Angeles County Jail, 2002-2012.

OBJECTIVES: We describe and report findings from a screening program to identify sexually transmitted infections (STIs) and HIV among female inmates in Los Angeles County Jail. METHODS: Chlamydia and gonorrhea screening was offered to entering female inmates. Women were eligible if they were (1) aged 30 years or younger, or (2) pregnant or possibly pregnant, or (3) booked on prostitution or sex-related charges. Voluntary syphilis and HIV testing was offered to all women between 2006 and 2009. This analysis reports on data collected from 2002 through 2012. RESULTS: A total of 76,207 women participated in the program. Chlamydia prevalence was 11.4% and gonorrhea was 3.1%. Early syphilis was identified in 1.4% (141 of 9733) and the overall prevalence of HIV was 1.1% (83 of 7448). Treatment levels for early syphilis and HIV were high (99% and 100%, respectively), but only 56% of chlamydia and 58% of gonorrhea cases were treated. CONCLUSIONS: Screening incarcerated women in Los Angeles County revealed a high prevalence of STIs and HIV. These inmates represent a unique opportunity for the identification of STIs and HIV, although strategies to improve chlamydia and gonorrhea treatment rates are needed.

Low Po2 conditions induce reactive oxygen species formation during contractions in single skeletal muscle fibers.

Contractions in whole skeletal muscle during hypoxia are known to generate reactive oxygen species (ROS); however, identification of real-time ROS formation within isolated single skeletal muscle fibers has been challenging. Consequently, there is no convincing evidence showing increased ROS production in intact contracting fibers under low Po2 conditions. Therefore, we hypothesized that intracellular ROS generation in single contracting skeletal myofibers increases during low Po2 compared with a value approximating normal resting Po2. Dihydrofluorescein was loaded into single frog (Xenopus) fibers, and fluorescence was used to monitor ROS using confocal microscopy. Myofibers were exposed to two maximal tetanic contractile periods (1 contraction/3 s for 2 min, separated by a 60-min rest period), each consisting of one of the following treatments: high Po2 (30 Torr), low Po2 (3-5 Torr), high Po2 with ebselen (antioxidant), or low Po2 with ebselen. Ebselen (10 µM) was administered before the designated contractile period. ROS formation during low Po2 treatment was greater than during high Po2 treatment, and ebselen decreased ROS generation in both low- and high-Po2 conditions (P < 0.05). ROS accumulated at a faster rate in low vs. high Po2. Force was reduced >30% for each condition except low Po2 with ebselen, which only decreased ~15%. We concluded that single myofibers under low Po2 conditions develop accelerated and more oxidative stress than at Po2 = 30 Torr (normal human resting Po2). Ebselen decreases ROS formation in both low and high Po2, but only mitigates skeletal muscle fatigue during reduced Po2 conditions.

Prevalence and factors associated with Trichomonas vaginalis infection among high-risk women in Los Angeles.

Remnant specimen from 1215 women screening for chlamydia/gonorrhea at 4 different venue types (sexually transmitted disease clinics, home-test kit users, juvenile and adult detention) in Los Angeles, California, were tested for Trichomonas vaginalis. Prevalence of T. vaginalis varied by screening population, and concurrent chlamydia or gonorrhea was independently associated with T. vaginalis.

Prevalence and correlates of rectal Chlamydia and gonorrhea among female clients at sexually transmitted disease clinics.

BACKGROUND: The prevalence and correlates of rectal sexually transmitted infections are well described among men who report receptive anal intercourse (AI); however, little is known about the epidemiology of rectal sexually transmitted infections among women. METHODS: We conducted a cross-sectional study of women attending public sexually transmitted disease clinics in Los Angeles County, California. Women were eligible for inclusion in this study if they reported AI in the previous 90 days, were tested for rectal chlamydia and gonorrhea, and were seen between January 2008 and December 2010. RESULTS: Among the 2084 clinic visits by women in this analysis, chlamydia and gonorrhea percent positivity by anatomic site was 12% (n = 144) for urogenital chlamydia, 14.6% (n = 171) for rectal chlamydia, 3.3% (n = 66) for urogenital gonorrhea, and 3.0% (n = 60) for rectal gonorrhea, with 25% of chlamydia cases and 19% of gonorrhea cases having rectal-only infections. Among women 25 years or younger, rectal infections were higher in visits in which women reported sex with an injection drug user (46.5% vs. 15.5%; P < 0.01) or sex with a HIV-positive partner (66.7% vs. 15.8%; P = 0.02). Among women older than 25 years, rectal infections were higher in visits where women reported substance use (10.6% vs. 5.8%; P ≤ 0.01). In multivariable models controlling for age and the presence of a urogenital infection, these associations remained. CONCLUSIONS: Chlamydia and gonorrhea positivity was high among women reporting AI, and a large proportion of these cases would be missed in the absence of rectal testing. The high-risk behaviors of women with rectal infections highlight the need for rectal screening recommendations.

Sexually transmitted infections and HIV prevalence among incarcerated men who have sex with men, 2000-2005.

OBJECTIVE: : Screening incarcerated populations, particularly men who have sex with men (MSM), for the identification, treatment, and prevention of sexually transmitted infections (STI) and HIV provides an effective way to access a hard-to-reach, high-risk population. GOAL: : To describe findings from a screening program designed to identify STIs and HIV among incarcerated MSM. STUDY DESIGN: : The Los Angeles County Sexually Transmitted Disease Program implemented a voluntary HIV and STI screening program in the segregated MSM unit of the Los Angeles County Men's Jail in March 2000. This analysis reports on data collected through December 2005. RESULTS: : Between March 2000 and December 2005, a total of 7004 inmates participated in the screening program. The overall positivity rate for chlamydia was 3.1% (127 of 4157) and 1.7% (69 of 4106) for gonorrhea. In addition, early syphilis was identified in 1.6% of inmates (95 of 6008) and the overall prevalence of HIV was 13.4% (625 of 4658). The level of repeat testing was relatively high with 15% (1048) of inmates repeatedly incarcerated and screened for STIs over the 5-year period. Although the seroprevalence of HIV was not significantly different between repeaters and nonrepeaters, 33 inmates were HIV seropositive after having tested negative at prior bookings, resulting in an HIV incidence of 1.9%. CONCLUSIONS: : Screening incarcerated MSM in Los Angeles revealed a high prevalence of STI and HIV infection. These inmates not only represent a high-risk group, but also a unique opportunity for the identification, treatment, and counseling of this hard-to-reach, high-risk population.

Strategies used in the detection of acute/early HIV infections. The NIMH Multisite Acute HIV Infection Study: I.

Acute/early HIV infection plays a critical role in onward HIV transmission. Detection of HIV infections during this period provides an important early opportunity to offer interventions which may prevent further transmission. In six US cities, persons with acute/early HIV infection were identified using either HIV RNA testing of pooled sera from persons screened HIV antibody negative or through clinical referral of persons with acute or early infections. Fifty-one cases were identified and 34 (68%) were enrolled into the study; 28 (82%) were acute infections and 6 (18%) were early infections. Of those enrolled, 13 (38%) were identified through HIV pooled testing of 7,633 HIV antibody negative sera and 21 (62%) through referral. Both strategies identified cases that would have been missed under current HIV testing and counseling protocols. Efforts to identify newly infected persons should target specific populations and geographic areas based on knowledge of the local epidemiology of incident infections.

PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ∼30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses.

"Optimal" cytoreduction for advanced epithelial ovarian cancer: a commentary.

OBJECTIVE: To derive the most appropriate threshold to classify primary cytoreductive operations as "optimal" and address the clinical significance of this issue. METHODS: Criteria used to classify primary cytoreductive outcomes are reviewed. Survival outcomes are analyzed to address relative influences of the completeness of cytoreduction and "biological aggressiveness", as manifested by the extent of intra-abdominal metastases. RESULTS: Most cohorts analyzing relative influences of metastatic tumor burden and the dimension of residual disease on survival report completeness of cytoreduction to influence the prognosis more significantly than tumor burden, with necessity to perform various procedures having minimal or no influence. Equivalent survival is reported for completely cytoreduced patients with stage III disease whether substages IIIa/b (smaller tumor burden) are excluded or included. However, some stage IIIc series report more favorable median and 5-year survivals for small fractions of completely cytoreduced patients than series with a large visibly disease-free fraction. Increasing fractions of complete cytoreduction are reported in recent cohorts, without increase in morbidity. CONCLUSIONS: Complete primary cytoreduction improves the prognosis for survival significantly more than a small dimension of residual disease. Although prospective randomized trials addressing surgical issues have not been undertaken and numerous variables may reflect "biological aggressiveness" by influencing the prognosis, available data justify elimination of macroscopic disease to be the most appropriate objective of primary cytoreductive surgery. Stratification of survival by dimensions of residual disease in an investigational setting should include a visibly disease-free subgroup and if used, the term "optimal" should be applied to patients undergoing complete cytoreduction.

Splenectomy in the context of primary cytoreductive operations for advanced epithelial ovarian cancer.

OBJECTIVE: To determine if the need to perform splenectomy due to metastatic disease in the context of complete primary cytoreduction for ovarian cancer diminishes the prognosis for survival. METHODS: Between 1990 and 2004, 356 stage IIIC epithelial ovarian cancer patients underwent resection of all visible disease before systemic platinum-based combination chemotherapy. Forty-nine (13.8%) required a splenectomy due to metastatic disease. Survival was analyzed (log rank) on the basis of whether splenectomy was necessary. The frequency of performing other procedures, operative time, blood loss, transfusion rate, and hospitalization, was compared (Chi-square test; discrete and binomial data, t test; continuous data) on the basis of whether a splenectomy was required. RESULTS: Survival was not influenced (log rank) by the requirement of splenectomy (required; median 56.4 months, estimated 5-year survival of 48% vs. not required; median 76.8 months, estimated 5-year survival of 58% P = 0.4). The splenectomy subgroup more commonly required en-bloc resection of reproductive organs with rectosigmoid (89.8% vs. 55.7%, P < 0.001), diaphragm stripping (63.3% vs. 33.6%, <0.001)), full-thickness diaphragm resection (28.6% vs. 9.4%, P < 0.001), and resection of grossly positive retroperitoneal nodes (67.3% vs. 46.3%, P = 0.006). The splenectomy group had a longer operative time (238 min vs. 192 min, P = 0.004), estimated blood loss (1663 ml vs. 1167 ml, P = 0.001), transfusion rate (5.3 units prbc vs. 3.2 units prbc, P = 0.002), and hospitalization (16.1 vs. 12.2 days P = 0.001). CONCLUSIONS: The need for splenectomy to achieve complete cytoreduction is a reflection of advanced disease but is not a manifestation of tumor biology precluding long-term survival.

Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients.

OBJECTIVE: To analyze prognostic factors influencing pancreatic cancer survival following curative resection, using prospectively collected, population-based data. SUMMARY BACKGROUND DATA: Several studies have analyzed the determinants of long-term survival in postresection pancreatic cancer patients, but the majority of these have been single-institutional chart reviews yielding inconsistent results. METHODS: This retrospective cohort study examined 396 Medicare-eligible patients over age 65 who were diagnosed with nonmetastatic pancreatic adenocarcinoma and who underwent surgical resection with curative intent while residing in one of the 11 Survival, Epidemiology, and End Results (SEER) registries between January 1991 and December 1996. Linked Medicare data provided information on treatment and comorbidity, while linked census tract data supplied sociodemographic characteristics. RESULTS: Median survival for the overall study population was 17.6 months, with 1- and 3-year survival rates of 60.1% and 34.3%, respectively. Survival appears to be gradually improving over time, concomitant with a rise in the proportion of patients undergoing surgery in teaching centers. Prognostic variables significantly diminishing survival on univariate analysis included African American race, treatment not in a teaching hospital, lack of adjuvant chemoradiation therapy, as well as histopathologic factors that included tumor size larger than 2 cm in diameter, moderate to poor histologic grade, and positive lymph node metastases. Higher socioeconomic status was associated both with an increased likelihood of receiving adjuvant therapy and improved overall survival. Multivariate analyses indicated the strongest predictors of survival were adjuvant combined chemoradiotherapy, small tumors (<2 cm in diameter), negative lymph nodes, well-differentiated histology, undergoing surgery in a teaching hospital, and high socioeconomic status. CONCLUSIONS: Although biologic characteristics remain important predictors of survival for patients with resected pancreatic cancer, the most powerful determinant is postoperative adjuvant chemoradiation therapy. An interesting finding that warrants further investigation is the effect of socioeconomic status on both the likelihood of receiving adjuvant treatment and subsequent survival, indicating a possible relationship between the quality of care delivered and outcomes.

Reduction of blood loss during extensive pelvic procedures by aortic clamping--a preliminary report.

OBJECTIVE: The aim was to determine the effect of intraoperative aortic clamping during extensive pelvic procedures on blood loss, operative time, and morbidity. METHODS AND MATERIALS: Thirteen women with ovarian cancer, 1 with cervical cancer, and 1 with an extensive pelvic sarcoma had their aortas completely occluded with a vascular clamp before the pelvic phases of their operations. Heparin and protamine reversal were used. RESULTS: Patients requiring en bloc excision of the internal reproductive organs, pelvic peritoneum, and recto-sigmoid colon in the context of a cytoreductive operation had a median estimated total blood loss of 650 ml (range 200 to 3500), a median of 2 units (range 0 to 8) of blood transfused, and a median total operative time of 155 min (range 90 to 280). There were no complications due to the aortic clamping. CONCLUSION: Most procedures were completed with a less than anticipated blood loss and operative time. Clamping of the aorta may potentially diminish blood loss, operative time, and the incidence of transfusion-related morbidity associated with extensive pelvic operations. Intraoperative aortic clamping merits further investigation.

Relative influences of tumor volume before surgery and the cytoreductive outcome on survival for patients with advanced ovarian cancer: a prospective study.

OBJECTIVE: The purpose of this study was to determine the relative influences of the extent of disease present before surgery and completeness of cytoreduction on survival for patients with advanced ovarian cancer. METHODS: Patients (408) with stage IIIC epithelial ovarian cancer had cytoreductive surgery before systemic platinum-based combination chemotherapy. A ranking system (0-3) was devised to prospectively quantify the extent of disease involving: (1) right upper quadrant (diaphragm/hepatic, and adjacent peritoneal surfaces), (2) left upper quadrant (omentum/gastro-colic ligament, spleen, stomach, transverse colon, splenic flexure of colon), (3) pelvis (reproductive organs, recto-sigmoid, pelvic peritoneum), (4) retroperitoneum (pelvic/aortic nodes), and (5) central abdomen (small bowel, ascending/descending colon, mesentery, anterior abdominal wall, pericolic gutters). Survival was analyzed (log rank and Cox regression) on the basis of the rankings at these anatomic regions, the sum of intraabdominal rankings, and the cytoreductive outcome. RESULTS: Overall median and estimated 5-year survivals were 58.2 months and 49%. On univariate analysis, the central abdominal (P = 0.008) and left upper quadrant (P = 0.03) rankings, the sum of rankings (P = 0.01), and the cytoreductive outcome (P 1 cm residual, RR 2.98; P = 0.001). CONCLUSIONS: Cytoreduction to a visibly disease-free outcome has a more significant influence on survival than the extent of metastatic disease present before surgery. Operative efforts should not be abbreviated on the hypothesis that extensive disease at specific anatomic regions precludes long-term survival.