Efficient termination of cardiac arrhythmias using optogenetic resonant feedback pacing.

Malignant cardiac tachyarrhythmias are associated with complex spatiotemporal excitation of the heart. The termination of these life-threatening arrhythmias requires high-energy electrical shocks that have significant side effects, including tissue damage, excruciating pain, and worsening prognosis. This significant medical need has motivated the search for alternative approaches that mitigate the side effects, based on a comprehensive understanding of the nonlinear dynamics of the heart. Cardiac optogenetics enables the manipulation of cellular function using light, enhancing our understanding of nonlinear cardiac function and control. Here, we investigate the efficacy of optically resonant feedback pacing (ORFP) to terminate ventricular tachyarrhythmias using numerical simulations and experiments in transgenic Langendorff-perfused mouse hearts. We show that ORFP outperforms the termination efficacy of the optical single-pulse (OSP) approach. When using ORFP, the total energy required for arrhythmia termination, i.e., the energy summed over all pulses in the sequence, is 1 mJ. With a success rate of 50%, the energy per pulse is 40 times lower than with OSP with a pulse duration of 10 ms. We demonstrate that even at light intensities below the excitation threshold, ORFP enables the termination of arrhythmias by spatiotemporal modulation of excitability inducing spiral wave drift.

New High Pressure Phases of Energetic Material TEX: Evidence from Raman Spectroscopy, X-ray Diffraction, and First-Principles Calculations.

Samples of energetic material TEX (C6H6N4O8) are studied using Raman spectroscopy and X-ray diffraction (XRD) up to 27 GPa pressure. There are clear changes in the Raman spectra and XRD patterns around 2 GPa related to a conformational change in the TEX molecule, and a phase transformation above 11 GPa. The molecular structures and vibrational frequencies of TEX are calculated by density functional theory based Gaussian 09W and CASTEP programs. The computed frequencies compare well with Raman spectroscopic results. Mode assignments are carried out using the vibrational energy distribution analysis program and are also visualized in the Materials Studio package. Raman spectra of the high pressure phases indicate that the sensitivity of these phases is more than that of the ambient phase.

Isolation and characterization of pathogenic Vibrio alginolyticus from sea cage cultured cobia (Rachycentron canadum (Linnaeus 1766)) in India.

Mass mortalities of cobia, Rachycentron canadum, sub-adults occurred during August 2013 in cage culture in the Gulf of Mannar, Mandapam Tamil Nadu, India. The epizootic of disease was started with typical classical clinical signs followed by acute mortality. Grossly, severe haemorrhage and congestion were observed in the gastric mucosa. The abdomen was distended with peritoneal fluid. The heart revealed haemopericardium and fibrinous pericardium. Histologically, the gastric mucosa showed severe erosion and necrosis. Haemorrhagic pericarditis and an increased size of the melano macrophage centre (MMC) in the tail kidney were other histopathological changes. Vibrio sp. was isolated from the gastric lesions and heart blood swab of moribund fishes and it was found to be virulent to the cobia fingerlings. After the challenge, the same bacterium could be re-isolated from moribund fingerlings. The 16S ribosomal RNA of the isolate was amplified and blast analysis of the sequence confirmed that the pathogen was Vibrio alginolyticus. The confirmation was also correlated with its cultural, biochemical and pathomorphological changes. This is the second report and the first incidence of epizootics with severe pathological lesions in cultured cobia in India. The study throws light on the pathology of vibriosis. By practising cage farm management measures, occurrences of infection may be prevented. SIGNIFICANCE AND IMPACT OF THE STUDY: The epizootics of vibriosis caused serious economic losses to farmers. Natural blooms of the pathogen can be prevented by sea cage management measures such as, changing the inner net of the cages, changing the location of the cages to relatively clean water (about 50 m apart) from the affected site and providing shade over the cages while the water temperature rises. Supplementation of the feed with immunostimulants and mineral mixture may be practised to improve the immune response against infection. Early diagnosis and sea cage management measures may prevent occurrences of the infection.

The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population.

BACKGROUND: Sexually transmitted infection with the human papillomavirus (hpv) is responsible for a significant burden of human cancers involving the cervix, anogenital tract, and oropharynx. Studies in the United States and Europe have demonstrated an alarming increase in the frequency of hpv-positive oropharyngeal cancer, but the same direct evidence does not exist in Canada. METHODS: Using the London Health Sciences Centre pathology database, we identified tonsillar cancers diagnosed between 1993 and 2011. Real-time polymerase chain reaction was then used on pre-treatment primary-site biopsy samples to test for dna from the high-risk hpv types 16 and 18. The study cohort was divided into three time periods: 1993-1999, 2000-2005, and 2006-2011. RESULTS: Of 160 tumour samples identified, 91 (57%) were positive for hpv 16. The total number of tonsillar cancers significantly increased from 1993-1999 to 2006-2011 (32 vs. 68), and the proportion of cases that were hpv-positive substantially increased (25% vs. 62%, p < 0.002). Those changes were associated with a marked improvement in 5-year overall survival (39% in 1993-1999 vs. 84% in 2006-2011, p < 0.001). When all factors were included in a multivariable model, only hpv status predicted treatment outcome. INTERPRETATION: The present study is the first to provide direct evidence that hpv-related oropharyngeal cancer is increasing in incidence in a Canadian population. Given the long lag time between hpv infection and clinically apparent malignancy, oropharyngeal cancer will be a significant clinical problem for the foreseeable future despite vaccination efforts.

Reduction of vibration and noise pollution from agricultural tractor engine using novel pine oil and soapnut oil methyl ester as fuel.

The exhaust emissions from automotive diesel engines are successfully controlled over the years by adopting different combustion strategies and after treatment devices, whereas the combustion induced vibration and noise are the major pollutant in off-road vehicle engines and yet to be optimized. In the present study, a twin cylinder, Simpson's S-217 tractor diesel engine was used to evaluate the performance, combustion, vibration, and noise characteristics, using biofuel blends. For this study, the blends of pine oil - soapnut oil biodiesel (P75SNB25), diesel - soapnut oil biodiesel (SNB20) and diesel were used as fuel. The pine oil used in this research was purchased and used in its neat form. The soapnut oil was extracted from the soapnut seeds by cold pressing method and trans-esterified in two stages by using methanol and catalysts. The experimental results revealed that the performance and combustion characteristics of the blend P75SNB25 was superior to diesel and the blend SNB20 was slightly inferior to diesel. For the blend P75SNB25, the amplitude of acceleration with respect to time was reduced by 19.48% and 11.58% at no load and full load conditions respectively, whereas for the blend SNB20, the amplitude of acceleration showed a reduction of 14.27% and 9.46% at no load and full load conditions respectively in comparison with diesel operation. But both the blends P75SNB25 and SNB20 showed a maximum reduction of noise by 2.34% at different engine loads compared to diesel operation.

FTIR spectroscopy as a convenient tool for detection and identification of airborne Cr(VI) compounds arising from arc welding fumes.

Given the significant presence of the carcinogenic Cr(VI) in arc welding fumes from stainless steels, it is also important, in addition to estimating the Cr(VI) levels, to identify Cr(VI) compounds, as it throws light on the mechanistic pathways towards fume formation. FTIR data is presented in this paper for arc welding fumes collected from Manual Metal Arc Welding (MMA), Flux Cored Arc Welding (FCAW) and Solid Wire Welding (Metal Inert/ Active Gas Welding [MIG/ MAG]). For MMA and FCAW samples, clear spectra corresponding to Na, K, dichromates was observed at wave number of around 725-740 cm-1 and at 890-900 cm-1. Chromate species were also observed at around 850-855 cm-1, as was evidence of CrO3 (chromium trioxide) too (950-970 cm-1). The identification of these compounds was done by carefully identifying the Cr-O-Cr anti-symmetric vibrations, the symmetric stretching of the CrO4 tetrahedra, and the stretching vibrations of the planar CrO3 structure for the chromium trioxide. All the above compounds were volatile, and present as nanoparticles in welding fumes, thereby potentially causing significant harm to the welders. Additionally, crystalline phases (Fe-Mn spinels) were also observed through powder XRD, and the data was compared with ion chromatography estimates for Cr(VI) and found to be consistent.

Effect of positioning from supine and left lateral positions to left lateral tilt on maternal blood flow velocities and waveforms in full-term parturients.

Positioning the parturient from supine to the left lateral tilt position (supine-to-tilt) may not effectively displace the gravid uterus, but turning from the left lateral position to the left lateral tilt position (left lateral-to-tilt) may keep the gravid uterus displaced and prevent aortocaval compression. Fifty-one full-term parturients were randomly placed in the left lateral position, supine-to-tilt and left lateral-to-tilt positions using a Crawford wedge. Femoral vein area, femoral vein velocity, femoral artery area, pulsatility index, resistance index and right arm mean arterial blood pressure and heart rate were recorded. Our results showed a lower mean (SD) femoral vein area (82.2 (14.9) vs 96.2 (16.4) mm(2)), a lower pulsatility index (3.83 (1.3) vs 5.8 (2.2)), a lower resistance index (0.93 (0.06) vs 0.98 (0.57)), a higher femoral artery area (33.3 (3.8) vs 30.9 (4.4) mm(2)) and a higher femoral vein velocity (7.9 (1.2) vs 6.1 (1.6) cm.s(-1)) with left lateral-to-tilt when compared with supine-to-tilt (all p < 0.001). Our results suggest that moving a full-term parturient from the full left lateral to the lateral tilt position may prevent aortocaval compression in full-term parturients more efficiently than when positioning the parturient from a supine to left lateral tilt position.

Physiotherapy interventions for head and trunk control in children with developmental disabilities: A scoping review protocol.

Background: Head and trunk control is prerequisite skill that maximizes engagement and participation in one's environment by integrating vision, oromotor skill, arm control and respiration. Various physiotherapy and technology-based interventions have been utilized to facilitate head and trunk control in children with developmental disabilities. This scoping review is planned to map and summarize existing studies from the scientific literature on physiotherapy and technology-based interventions for head and trunk control in children with developmental disabilities. Methods: The scoping review will utilize the Joanna Briggs Institute scoping review methodology. The review will cover studies including children and adolescents aged between six months and 17 years 11 months 29 days, with developmental disabilities where in child finds difficulty in lifting its head and aligning head and trunk. We will include randomized controlled trial (RCT), non-RCT, quasi-experimental trial, and systematic reviews that have employed physiotherapy and technology-based interventions. Database-specific search strategy will be used to search records in Medline (PubMed and Web of Science), Embase, Scopus, CINAHL, PEDro, and Cochrane Library. Additionally, various grey literatures and clinical-trial registries will be searched. Two reviewers, independently, will screen and extract the data. Tables and visual representations will be utilized to present the extracted data. Registration details: The protocol has been registered in Open Science Framework, DOI:  10.17605/OSF.IO/B3RSU (22 nd August 2022).

Comparison of adipocyte-specific gene expression from WNIN/Ob mutant obese rats, lean control, and parental control.

Adipose tissue development is a highly regulated phenomenon orchestrated by several check points (recruitment of mesenchymal stem cells and their lineage commitment) to form mature adipocytes. Once committed to obesity, expansion of adipose tissue occurs either by hypertrophy or hyperplasia or by both resulting in an altered physiological status. This precipitates as inflammatory responses, leading to endoplasmic reticulum and oxidative stress altering the gene expression of adipose tissue in a depot-specific manner. However, such studies reporting a phased gene expression profile in conditions of rodent obesity are not reported so far. WNIN/Ob mutant obese rat, developed at our institute is an excellent model to study the pathophysiological changes underlying obesity. Here, we report the gene expression profile of this mutant rat (obese and lean), compared with the parental control, with reference to markers of embryonic stem cells, adipogenesis, inflammation, and senescence in both subcutaneous (SCAT) and retroperitoneal (RPAT) adipose depots representing abdominal fat. We demonstrate an upregulation of genes such as Sox-2, Pref-1, PPARγ2, LPL, IRS-1, GLUT-4, IL-6, TNFα, and telomerase in SCAT and RPAT depots of the obese rat compared to its lean counterpart indicating no difference in fat depots at different locations. This is suggestive of a similar phenotypic expression of mutant gene. Data form the phased gene expression changes of adipogenesis (embryonic/adipogenic/inflammatory) in the present obese rat model system advocate for inflammatory mediated response(s) associated with obesity-a condition often seen in humans.

Delay in diagnosis of patients with head-and-neck cancer in Canada: impact of patient and provider delay.

Background: Head-and-neck cancers (hncs) often present at an advanced stage, leading to poor outcomes. Late presentation might be attributable to patient delays (reluctance to seek treatment, for instance) or provider delays (misdiagnosis, prolonged wait time for consultation, for example). The objective of the present study was to examine the length and cause of such delays in a Canadian universal health care setting. Methods: Patients presenting for the first time to the hnc multidisciplinary team (mdt) with a biopsy-proven hnc were recruited to this study. Patients completed a survey querying initial symptom presentation, their previous medical appointments, and length of time between appointments. Clinical and demographic data were collected for all patients. Results: The average time for patients to have their first appointment at the mdt clinic was 15.1 months, consisting of 3.9 months for patients to see a health care provider (hcp) for the first time since symptom onset and 10.7 months from first hcp appointment to the mdt clinic. Patients saw an average of 3 hcps before the mdt clinic visit (range: 1-7). No significant differences in time to presentation were found based on stage at presentation or anatomic site. Conclusions: At our tertiary care cancer centre, a patient's clinical pathway to being seen at the mdt clinic shows significant delays, particularly in the time from the first hcp visit to mdt referral. Possible methods to mitigate delay include education about hnc for patients and providers alike, and a more streamlined referral system.

A study to explore the factors related to treatment seeking delay among adults diagnosed with acute myocardial infarction at KMCH, Coimbatore.

OBJECTIVE: The main aim of the study was to explore the factors causing delay in seeking treatment among adult patients diagnosed with CAAs acute myocardial infarction (AMI) and compare the factors between timely and late treatment seeking groups. METHOD: A total of 93 subjects were included in the study diagnosed with AMI interviewed within 48h of hospitalization. Data were collected from onset of symptoms to arrival at hospital on demography, clinical profile, clinical factors, cognitive factors and social support factors. Subjects were categorized in two study groups i.e. timely treatment seeking group (<120min from onset of symptoms) and delayed treatment seeking group (>120min from onset of symptoms). RESULTS: The minimum and maximum time took by subjects to seek treatment was 10 and 5450min, respectively. The mean pain score of subjects who sought delayed treatment (2.2619) is less than those who sought timely treatment (3.3725). The mean knowledge score (12.2754), mean symptom perception (3.6667), mean perceived seriousness (4.7647) is more in subjects who sought timely treatment than those who sought delayed treatment (5.7381), (1.3095), (1.8333) respectively. The mean family support score (57.4492), mean non-family support score (24.902), mean social support score (48.3002) is more in timely treatment group than in delayed treatment seeking group (42.6829), (4.7619), (29.2138) respectively. CONCLUSION: Decreased pain, knowledge about AMI, symptom perception, perceived seriousness respectively and inadequate family & non-family support i.e. social support were the factors related to treatment seeking delay among adults diagnosed with AMI.

Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: Radiation Therapy Oncology Group Trial 92-02.

PURPOSE: The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT) -treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. PATIENTS AND METHODS: There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. RESULTS: Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P =.08), BF (P =.0445), DM (P <.0001), CSD (P <.0001), and OD (P =.0094). When categoric variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The 7.1% cut point was related to BF (P =.09), DM (P =.0008), and CSD (P =.017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. CONCLUSION: Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.

The significance of circulating tumor cells in prostate cancer patients undergoing adjuvant or salvage radiation therapy.

BACKGROUND: Following radical prostatectomy, success of adjuvant and salvage radiation therapy (RT) is dependent on the absence of micrometastatic disease. However, reliable prognostic/predictive factors for determining this are lacking. Therefore, novel biomarkers are needed to assist with clinical decision-making in this setting. Enumeration of circulating tumor cells (CTCs) using the regulatory-approved CellSearch System (CSS) is prognostic in metastatic prostate cancer. We hypothesize that CTCs may also be prognostic in the post-prostatectomy setting. METHODS: Patient blood samples (n=55) were processed on the CSS to enumerate CTCs at 0, 6, 12 and 24 months after completion of RT. CTC values were correlated with predictive/prognostic factors and progression-free survival. RESULTS: CTC status (presence/absence) correlated significantly with positive margins (increased likelihood of CTC(neg) disease; P=0.032), and trended toward significance with the presence of seminal vesicle invasion (CTC(pos); P=0.113) and extracapsular extension (CTC(neg); P=0.116). Although there was a trend toward a decreased time to biochemical failure (BCF) in baseline CTC-positive patients (n=9), this trend was not significant (hazard ratio (HR)=0.3505; P=0.166). However, CTC-positive status at any point (n=16) predicted for time to BCF (HR=0.2868; P=0.0437). CONCLUSIONS: One caveat of this study is the small sample size utilized (n=55) and the low number of patients with CTC-positive disease (n=16). However, our results suggest that CTCs may be indicative of disseminated disease and assessment of CTCs during RT may be helpful in clinical decision-making to determine, which patients may benefit from RT versus those who may benefit more from systemic treatments.

A Phase 1/2 Trial of Brief Androgen Suppression and Stereotactic Radiation Therapy (FASTR) for High-Risk Prostate Cancer.

PURPOSE: To initiate a phase 1/2 trial to examine the tolerability of a condensed combined-modality protocol for high-risk prostate cancer. METHODS AND MATERIALS: Men scoring ≥3 on the Vulnerable Elderly Scale (VES) or refusing conventionally fractionated treatment for high-risk prostate cancer were eligible to participate. Androgen suppression was delivered for 12 months, and radiation therapy was delivered using 25 Gy to pelvic nodes delivered synchronously with 40 Gy to the prostate given as 1 fraction per week over 5 weeks. The phase 1 component included predetermined stopping rules based on 6-month treatment-related toxicity, with trial suspension specified if there were ≥6 of 15 patients (40%) or ≥3 of 15 (20%) who experienced grade ≥2 or ≥3 gastrointestinal (GI) or genitourinary (GU) toxicity, respectively. RESULTS: Sixteen men were enrolled, with 7 men meeting the criteria of VES ≥3 and 9 men having a VES <3 but choosing the condensed treatment. One man was not treated owing to discovery of a synchronous primary rectal cancer. Four patients (26%) experienced grade ≥2 toxicity at 6 weeks after treatment. There were 9 of 15 (60%) who experienced grade ≥2 GI or GU toxicity and 4 of 15 (26%) grade ≥3 GI or GU toxicity at 6 months, and 5 of 15 (30%) grade ≥2 GI and GU toxicity at 6 months. A review of the 15 cases did not identify any remedial changes, thus the phase 1 criteria were not met. CONCLUSION: This novel condensed treatment had higher than anticipated late toxicities and was terminated before phase 2 accrual. Treatment factors, such as inclusion of pelvic lymph node radiation therapy, planning constraints, and treatment margins, or patient factors related to the specific frail elderly population may be contributing.

Method of localization and implantation of the lumpectomy site for high dose rate brachytherapy after conservative surgery for T1 and T2 breast cancer.

PURPOSE: This article describes our technique of localization and implantation of the lumpectomy site of patients with T1 and T2 breast cancer. Our method was developed as part of our Phase I/II pilot study of high dose rate (HDR) brachytherapy alone after conservative surgery for early breast cancer. METHODS AND MATERIALS: In March 1992, we started a pilot study of HDR brachytherapy to the lumpectomy site as the sole radiotherapy after conservative surgery for clinical T1 or T2 invasive breast cancer. Initially, the protocol required intraoperative placement of the interstitial needles at the time of definitive surgery to the breast. The protocol was then generalized to allow the implantation of the lumpectomy site after definitive surgery to the breast, either at the time of subsequent axillary nodal dissection or postoperatively. To date, five patients have been implanted intraoperatively at the time of definitive breast surgery. Twelve patients were implanted after definitive breast surgery, with 7 patients being done at the time of axillary nodal dissection and 5 patients postoperatively. We devised a method of accurately localizing and implanting the lumpectomy site after definitive breast surgery. The method relies on the previous placement of surgical clips by the referring surgeon to mark the lumpectomy site. For each patient, a breast mold is made with radio-opaque angiocatheters taped onto the mold in the supero-inferior direction. A planning CT scan is then obtained through the lumpectomy site. The volume of the lumpectomy site, the number of implant planes necessary, and the orientation of the implants are then determined from the CT scan. The angiocatheters provide a reference grid on the CT films to locate the entry and exit points of the interstitial needles on the plastic mold. The entry and exit points for reference needles are then transferred onto the patient's skin enabling implantation of the lumpectomy site. Needle positions with respect to the lumpectomy site are then verified using simulator radiographs. RESULTS: Eight double plane implants and four single plane implants have been done using this method. Five implants were done using direct visualization. It has not been necessary to reorient the implant in any of the patients. If not for the presence of surgical clips, the size of the lumpectomy site cannot be separated from the surrounding normal breast tissue. CONCLUSION: This technique is an accurate way to localize the lumpectomy site for HDR brachytherapy.

Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant systemic therapy alone: patterns of recurrence.

PURPOSE: Prognostic factors for locoregional failure have been poorly documented. The purpose of this retrospective review is to examine the patterns of failure of 320 patients with Stage II or III axillary node-positive breast cancer who received adjuvant chemotherapy without locoregional radiation. METHODS AND MATERIALS: The records of 735 patients who were referred to the London Regional Cancer Centre between 1980 and 1989 with a diagnosis of Stage II or III breast cancer were reviewed. Three hundred and twenty patients were identified who underwent segmental mastectomy with axillary dissection or modified radical mastectomy and adjuvant chemotherapy without adjuvant locoregional radiation. Seventy-one percent of these patients had undergone a modified radical mastectomy, 40% had T1 tumors, 49% T2, and 11% T3. Resection margins were positive in 13 patients. The median number of axillary nodes removed was 11. Fifty-four percent had one to three positive axillary nodes, 27% had four to seven positive nodes, and 19% had in excess of seven positive nodes. RESULTS: Median follow-up for the 320 patients was 77 months. One hundred and fourteen patients developed a locoregional recurrence as the site of first relapse (31 in the intact breast, 29 on the chest wall, 21 in the axilla, 22 in the supraclavicular fossa, 1 in the internal mammary chain, and 10 in multiple sites). Thirty-three percent of segmental mastectomy patients and 13% of modified radical mastectomy patients developed local recurrence. Seven percent of patients recurred in axillary or supraclavicular nodes each. Factors with regard to locoregional recurrence which on univariate analysis were significant included type of mastectomy (i.e., segmental vs. modified radical), size of primary tumor, positive resection margins, and percentage of ideal chemotherapy dose intensity (< 66% vs. > or = 66%). After multivariate analysis, only type of mastectomy, size of primary tumor, and percentage of ideal chemotherapy dose intensity retained significance. The number of positive axillary nodes was not a significant factor. Number of positive axillary nodes plus the above four clinical factors were analyzed in terms of regional recurrence specifically. By univariate and multivariate analysis, only size of primary tumor retained significance. Again, the number of positive axillary nodes was not a relevant factor. CONCLUSION: Patients receiving adjuvant chemotherapy who are at high risk of locoregional recurrence include those who undergo segmental mastectomy and those with larger tumors (> 5 cm in diameter). Breast or chest wall radiation is recommended for these groups. Supraclavicular radiation is recommended for patients with tumors larger than 5 cm in diameter. Axillary recurrences were relatively infrequent in patients who had undergone an adequate Level I and II axillary dissection, and therefore, axillary radiation was not recommended.

Extracapsular axillary node extension in patients receiving adjuvant systemic therapy: an indication for radiotherapy?

PURPOSE: This is a retrospective review into the patterns of failure of 82 patients with Stage II or III breast cancer who had extracapsular extension (ECE) of axillary nodal metastases and who received systemic chemotherapy or hormonal therapy without loco-regional radiation. METHODS AND MATERIALS: The clinical records of patients with axillary node positive (T1-T3, N1, 2) Stage II or III breast cancer seen at the London Regional Cancer Centre between 1980-1989 were reviewed. Patients were identified who underwent segmental mastectomy with axillary node dissection or modified radical mastectomy and received adjuvant chemotherapy or tamoxifen but did not undergo loco-regional radiation. Eighty-two patients within this group had pathologic evidence of extracapsular axillary node extension (ECE). For 45 of these patients the extension was extensive, and for the remaining 37 it was microscopic. This ECE-positive group was compared to a subgroup of 172 patients who did not have pathologic evidence of extracapsular axillary node extension but had metastatic carcinoma confined within the nodal capsule. RESULTS: Median age of the 82 ECE-positive patients was 56 years. Twenty-five patients had had a segmental mastectomy, the remainder a modified radical mastectomy. Median actuarial survival was 60 months, with a median disease-free and loco-regional failure-free survival of 38 months. Seventy-eight percent of these patients developed a recurrence, which was loco-regional in 60% (21% local, 21% regional, 2% local and regional, and 16% loco-regional and metastatic). There was a 36% recurrence rate in intact breast, 14% the chest wall following modified radical mastectomy, 7% relapsed in the axilla, 12% in supraclavicular nodes, and 1% in the internal mammary nodes. A comparison of the 82 ECE-positive patients with a group of 172 ECE-negative patients determined that there was a statistically significant difference between the two groups in terms of survival (overall and disease-free) and loco-regional recurrence. Univariate analysis of the entire 254 node-positive patient group revealed extracapsular nodal extension (ECE) to be a prognostically significant factor for actuarial and disease-free survival as well as for loco-regional failure, but ECE did not remain an independently prognostic factor after multivariate analysis. Segmental mastectomy, positive resection margins, and ER negative status increased the risk of loco-regional recurrence within the ECE-positive group. CONCLUSIONS: Extracapsular axillary node extension is a prognostically significant factor for actuarial survival, disease-free survival, and loco-regional failure but not independent of other adverse prognostic factors. It is a marker for increased loco-regional recurrence associated with doubling of breast, chest wall, and supraclavicular recurrence rates. The risk of axillary relapse in patients who have had an adequate level I and II axillary dissection but demonstrate extracapsular extension is low (7%). We recommend breast/chest wall and supraclavicular radiation for all patients with pathologic evidence of such extranodal extension who have had a level I and II axillary dissection regardless of the number of positive axillary nodes. Axillary irradiation should be considered for patients who have had only an axillary sampling or level I axillary dissection.

Postoperative radiotherapy for Stage I/II seminoma: results for 212 patients.

PURPOSE: A retrospective review of patients with Stage I and II seminoma treated at a regional cancer center was performed to assess the long term efficacy and toxicity associated with post operative radiotherapy. METHODS AND MATERIALS: Between 1950 and 1995, 212 patients seen at the London Regional Cancer Centre received adjuvant radiotherapy following orchiectomy for Stage I (169) and II (43) seminoma. Median follow-up for the group was 7.5 years. RESULTS: Progression free, cause specific, and overall survival were 95%, 98%, and 95% at 5 years, and 94%, 98%, and 94% at 10 years respectively. An increased risk of failure was noted among patients with bulky Stage II disease. No other prognostic factors for relapse were identified. Late toxicity was uncommon with only 12/212 (6%) developing any late GI toxicity potentially attributable to radiotherapy. The incidence of second malignancies (excluding second testicular tumors) was 6/212 (actuarial:1%, 1%, 6% at 5,10,15 years respectively). There was a trend toward increased acute complications for patients treated with larger volumes of radiation. No prognostic factors associated with increased risk of late toxicity or second malignancy were identified, likely a consequence of the small number of these events. CONCLUSION: Survival and toxicity were comparable to that reported in the literature. Post-operative radiotherapy remains a safe and efficacious adjuvant treatment for Stage I and early Stage II seminoma.

Prostate inhibin peptide (PIP) in prostate cancer: a comparative immunohistochemical study with prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP).

Prostate inhibin peptide (PIP) is a polypeptide synthesized by the prostate gland that is involved in prostatic growth and differentiation. The objective of this study was to evaluate PIP as an immunocytochemical marker for prostatic adenocarcinoma (PCA) by comparing it with PSA and PAP. A total of 71 cases of primary PCA and 5 cases of metastatic PCA were studied. Primary tumors were specially selected to include a disproportionate number of high-grade tumors. The distribution of cases by Gleason score was 2-5, 14 cases; 6-7, 24 cases; and 8-10, 33 cases. Four metastases were to bone (decalcified tissue) and one to soft tissue. All 71 cases of primary PCA stained positively for the three antibodies tested, with none demonstrating obvious superiority, although individual case variability was seen. In one bone metastasis, staining for PSA was negative, with both PAP and PIP giving positive results. All non-prostatic carcinomas tested were negative. These results indicate that PIP is as sensitive and specific an immunohistochemical marker as PSA and PAP in untreated prostate adenocarcinomas. Further, the androgen-independent nature of PIP may give it an advantage over PSA/PAP in tumors exposed to androgen ablating agents.

Vocal function following radiation for non-laryngeal versus laryngeal tumors of the head and neck.

OBJECTIVE: The larynx may receive high doses of radiation even in the absence of disease. Preliminary investigation has provided evidence that significant voice alterations exist in patients who received radiotherapy (RT) for non-laryngeal tumors of the head and neck. This study evaluates subjective and objective parameters of vocal function in this patient population compared with a control group of patients irradiated for early glottic tumors. STUDY DESIGN: Retrospective cohort study. METHODS: Vocal function in patients irradiated for non-laryngeal and early glottic tumors was assessed in a comprehensive manner and compared. Microanalytical and macroanalytical acoustic analyses, aerodynamic measurements, and videostroboscopy were performed on vowel production data. The Voice Handicap Index was administered for self-assessment of voice quality. All subjects were male, smokers, and greater than 12 months post-RT. RESULTS: Seventeen patients with non-laryngeal tumors and 13 patients with early glottic tumors were evaluated. Microanalytical acoustic parameters were worse for 75% (6 of 8) of the acoustic measures of vowel production in the non-laryngeal group. These include jitter, relative amplitude perturbation, amplitude perturbation quotient, normalized noise energy, pitch amplitude, and spectral flatness ratio. Macroanalytical acoustic analyses revealed no difference in fundamental frequency but numerically smaller phonational frequency range in the non-laryngeal group. All aerodynamic measures, including mean phonation time, mean airflow, and vocal fold diadochokinetic rate, were decreased in the non-laryngeal group. Videostroboscopy demonstrated increased supraglottic activity in the non-laryngeal group. Voice handicap was significantly greater in the non-laryngeal group. CONCLUSIONS: When compared with patients receiving RT for early glottic tumors, there is objective and subjective evidence of vocal dysfunction in patients treated with wide-field RT for non-laryngeal tumors.