Validation of the inverse water volumetry method: a new gold standard for arm volume measurements

Background No consensus exists with respect to a commonly accepted and standardized method for measuring arm volumes in patients with lymphedema. Knowing the exact volume in (potential) lymphedemic arms and comparing this volume with healthy arms is important to detect the first signs of lymphedema and to study the effects of treatment.Methods A new apparatus, based upon the principle of measuring shortness of water, was developed to measure arm volumes. This measuring-method, inverse water volumetry, was prospectively validated in patients, suffering from lymphedema after complete or partial mastectomy for primary breast cancer. Healthy and lymphedemic arm were measured 3 times: twice by nurse A (A1 and A2) and once by nurse B (B). Subsequently, these differences in volumes were compared with differences in volumes obtained by the Herpertz method, which is based upon circumferential measurement.Results In every patient at every occasion volume of the lymphedemic arm was bigger than the corresponding volume of the control arm. Mean volumes of healthy arms were 3958(A1), 3966(A2) and 3961(B) ml respectively. Mean volumes of lymphedemic arms were 4721(A1), 4752(A2) and 4773(B) ml respectively, volume B being significantly different from volume A1. Volume difference of edemic arms minus control arms was not significant between measurements (A1 vs. A2 and A1 vs. B, respectively), while this difference was significant (A1 vs. B) using the Herpertz method.Conclusion Inverse water volumetry is an easy measuring device with a high inter- and intra-observer agreement. The small but significant volume increase of lymphedemic arms in time compared to the constant volumes of control arms is as well indicative for the accuracy of the method as for the volume of lymphedemic arms to increase when no therapeutic garment is carried.     

Right and left breast volume and volume distribution comparisons in normal and tumor-containing breasts

A measurement technique involving the use of close-range stereophotogrammetry has been developed for the study of breast volume and volume distribution (shape) comparison. This biostereometric method has been shown to be able to measure volume to within 0.63% of that determined by water displacement. This study describes the rapid and non-invasive data acquisition methodology as well as the mathematical algorithms used to determine breast volume. Additionally, the paper discusses the application of this process to documenting the presence or absence of total volume and volume distribution differences existing in normal breasts and those containing benign and malignant tumors.     

The Addition of Manual Lymph Drainage to Compression Therapy For Breast Cancer Related Lymphedema: a Randomized Controlled Trial

PURPOSE: The purpose of this investigation was to compare the reduction in arm lymphedema volume achieved from manual lymph drainage massage (MLD) in combination with multi-layered compression bandaging (CB) to that achieved by CB alone. METHODS AND MATERIALS: Fifty women with lymphedema (mean age of 59 years +/- 13 years) were randomly assigned to 4 weeks of combined MLD/CB or CB alone. The primary study endpoint was the reduction in arm lymphedema volume, which was determined by water displacement volumetry and measurement of circumference. Independent assessors, blinded to subject treatment assignment, performed the outcome measurements. RESULTS: Arm lymphedema volume decreased significantly after 4 weeks irrespective of treatment assignment (p < 0.001). Individuals with mild lymphedema receiving combined MLD/CB had a significantly larger percentage reduction in volume compared to individuals with mild lymphedema receiving CB alone, and compared to individuals with moderate or severe lymphedema receiving either treatment. CONCLUSION: These findings indicate that CB, with or without MLD, is an effective intervention in reducing arm lymphedema volume. The findings suggest that CB on its own should be considered as a primary treatment option in reducing arm lymphedema volume. There may be an additional benefit from the application of MLD for women with mild lymphedema; however, this finding will need to be further examined in the research setting.     

Assessment of morphometric measurements of prostate carcinoma volume

BACKGROUND: The authors have shown that the primary determinants of prostate carcinoma progression are tumor volume and the percent of the tumor comprised of Gleason Grade 4/5 cells. In the current study the authors evaluated six different techniques for the morphometric measurements of prostate carcinoma volume. METHODS: A computer-assisted image analysis (NIH Image, developed and maintained by the National Institutes of Health, Bethesda, MD) was used to analyze all 108 step-sectioned prostate specimens obtained between January 1 and December 31, 1997. The authors used the Stanford technique of 0.3-cm step-sections, measuring the volume of the tumor at both 0.3-cm and 0.6-cm intervals. The other 4 methods included the authors' previous method based on an earlier image program, the ellipsoidal method (pi / 6 x width x height x length), an estimation of the square area of the largest tumor, and the maximum tumor dimension (MTD). RESULTS: The authors first checked the accuracy of NIH Image analysis by measuring 24 circles of widely different sizes. The mean coefficient of variation was 1.7% and the correlation between the mean circle areas measured by the NIH Image software and true circle area essentially was perfect (correlation coefficient [r] = 1 and r(2) = 0.999; P < 0.0001). In comparison with the authors' original computer image program using 0.3-cm step-sections measured by a different observer, r(2) with the NIH Image analysis was 0.93. Using NIH Image only, the 0.6-cm step-section method missed measurable cancers in 16.7% of 108 radical prostatectomies in comparison with the 0.3-cm step-method. The mean tumor volume with the 0.6-cm section method (P < 0.0001) and the ellipsoidal method (P < 0.05) were significantly higher than with the 0.3-cm section method. r(2) from linear regressions using the 0.3-cm step section method as the standard versus the ellipsoidal method was 0.594, and was 0.89 versus the 0.6-cm step-section method, 0.652 versus the square area estimation, and 0. 527 versus the MTD method. CONCLUSIONS: The results of the current study support NIH Image as a powerful software program for the morphometric measurement of prostate carcinoma volume. Pathologic processing with 0.3-cm section slices was found to be more accurate for tumor volume than the 0.6-cm section slices. The ellipsoidal method, the square area of the largest tumor, and the MTD all were found to be inferior to computer-assisted image analysis measurements. In certain clinical situations in which only estimates of tumor volume are required, the square area of the largest tumor appears to be the best choice (r(2) 0.652).     

Effect of upper extremity exercise on secondary lymphedema in breast cancer patients: a pilot study.

PURPOSE: To examine the effect of a progressive upper-body exercise program on lymphedema secondary to breast cancer treatment. METHODS: Fourteen breast cancer survivors with unilateral upper extremity lymphedema were randomly assigned to an exercise (n = 7) or control group (n = 7). The exercise group followed a progressive, 8-week upper-body exercise program consisting of resistance training plus aerobic exercise using a Monark Rehab Trainer arm ergometer. Lymphedema was assessed by arm circumference and measurement of arm volume by water displacement. Patients were evaluated on five occasions over the experimental period. The Medical Outcomes Trust Short-Form 36 Survey was used to measure quality of life before and after the intervention. Significance was set at alpha < or = 0.01. RESULTS: No changes were found in arm circumference or arm volume as a result of the exercise program. Three of the quality-of-life domains showed trends toward increases in the exercise group: physical functioning (P =.050), general health (P =.048), and vitality (P =.023). Mental health increased, although not significantly, for all subjects (P =.019). Arm volume measured by water displacement was correlated with calculated arm volume (r =.973, P <.001), although the exercise and control group means were significantly different (P <.001). CONCLUSIONS: Participation in an upper-body exercise program caused no changes in arm circumference or arm volume in women with lymphedema after breast cancer, and they may have experienced an increase in quality of life. Additional studies should be done in this area to determine the optimum training program.     

Factors associated with increased breast cancer-related lymphedema volume

BACKGROUND: Upper limb lymphedema occurs in approximately 15-20% of women after breast cancer treatment. We analysed the factors associated with lymphedema volume. METHOD: Cross-sectional study of 807 patients with secondary arm lymphedema was performed in a single lymphology unit. Data collected included patient characteristics, characteristics of breast cancer treatment, past history of cellulitis, Body Mass Index, delay from cancer to onset of lymphedema and duration of lymphedema. Lymphedema volume was calculated for each 5-cm segment by utilizing the formula for a truncated cone. Univariate and multivariate regression models were fitted to study the factors associated with increased lymphedema volume. RESULTS: In univariate analysis, factors associated with lymphedema volume were duration of lymphedema, Body Mass Index, mastectomy, and past history of cellulitis. Treatment with anti-estrogen drugs was negatively associated with lymphedema volume (p = 0.02). In multivariate analysis, factors associated with lymphedema volume were duration of lymphedema (p < 0.001), Body Mass Index (p < 0.001), delay from cancer to onset of lymphedema (p = 0.002), mastectomy (p = 0.02) and past history of cellulitis (p = 0.011). CONCLUSION: Early diagnosis and management of lymphedema, weight control and advices to avoid cellulitis are the main controllable parameters in women to prevent severity of breast cancer-related lymphedema.     

Liposuction gives complete reduction of chronic large arm lymphedema after breast cancer

About one-third of all women treated for breast cancer develop arm lymphedema. In addition to the worry of the cancer itself, the swollen and heavy arm is both a physical and a psychosocial handicap for the patients. Previous surgical and conservative treatments have not always given satisfactory and permanent results, conceivably because lymphedema causes hypertrophy of the subcutaneous adipose tissue. From this point of view, liposuction (LS) combined with Controlled Compression Therapy (CCT) is an interesting approach, as the hypertrophied adipose tissue is effectively removed and the outcome sustained by wearing a compression garment. Pre- and postoperative arm edema volumes were measured using the water displacement technique. Skin blood flow was recorded using Laser Doppler imaging. Lymph transport in the arm was assessed by indirect lymphoscintigraphy. LS + CCT reduced the arm edema volume completely, compared with a 50% decrease following CCT alone. The use of a compression garment after liposuction is necessary in order to maintain the normalized arm volume. LS + CCT did not affect the already impaired lymph transport; it merely increased skin microcirculation. A reduced incidence of cellulitis was noted.     

Preoperative anaplastic glioma tumor volume effects on patient survival

BACKGROUND AND OBJECTIVES: The relationship between preoperative tumor volume and patient survival has long been studied, but the results have been inconsistent. Since geometric measurement of tumor volume was used in these studies, the aim of this study was to ascertain whether the inconsistency of the study results is due to less accurate geometric measurement. METHODS: Prognostic tumor volume effects were compared between the planimetry method and the geometric method using survival analysis, performed for 99 patients diagnosed with anaplastic glioma tumor. RESULTS: A significant correlation was found between planimetry tumor volume and patient survival, but there was no correlation between geometric tumor volume and patient survival. The larger planimetry tumor volume was significantly associated with shorter survival. CONCLUSIONS: The study indicated that in brain tumor research the preoperative tumor volume measured by the geometric method may not be prognostically important. The more accurate measurement, i.e., the planimetry method (based on either computed tomography or magnetic resonance imaging), is needed in brain tumor clinical research and prognostic diagnosis.     

Decongestive lymphatic therapy for patients with breast carcinoma-associated lymphedema. A randomized,prospective study of a role for adjunctive intermittent pneumatic compression

BACKGROUND: Disruption of the lymphatic circulation through breast carcinoma-associated axillary lymph node dissection, with or without radiation therapy, reportedly is the most common cause of lymphedema in developed countries. There is no cure for breast carcinoma-associated lymphedema. Although intermittent pneumatic compression (IPC) has been acknowledged as a potential component of the multidisciplinary therapeutic strategy in the treatment of patients with breast carcinoma-associated lymphedema, prospective study of its adjunctive safety and efficacy is required. METHODS: IPC was assessed as a component of the initial therapeutic regimen for newly treated patients with breast carcinoma-associated lymphedema. Twenty-three patients who had not previously been treated for lymphedema were randomized to receive either decongestive lymphatic therapy (DLT) alone or DLT with daily adjunctive IPC. Patients with stable, treated, breast carcinoma-associated lymphedema also were assessed in the maintenance phase of therapy. Twenty-seven patients were randomized either to DLT alone or to DLT coupled with daily IPC. In both studies, objective assessment included serial measurement of volume by water displacement, tissue tonometry to assess elasticity of the skin, and goniometry to measure joint mobility. RESULTS: During initial treatment, the addition of IPC to standard DLT yielded an additional mean volume reduction (45.3% vs. 26%; P < 0.05). During maintenance DLT alone, there was a mean increase in volume (32.7 +/- 115.2 mL); with DLT and IPC, there was a mean volume reduction (89.5 +/- 195.5 mL; P < 0.05). In both studies, IPC was tolerated well without detectable adverse effects on skin elasticity or joint range of motion. CONCLUSIONS: When IPC is used adjunctively with other, established elements of DLT, it provides an enhancement of the therapeutic response. IPC is well tolerated and remarkably free of complications.     

Prospective trial of intensive decongestive physiotherapy for upper extremity lymphedema

BACKGROUND: The aim of this study was to evaluate the effects of kinesiophobia, quality of life, and home exercise programs on women with upper extremity lymphedema. METHODS: A total of 62 women with lymphedema after breast cancer treatments were provided a protocol of complete decongestive therapy (CDT). This protocol involved manual lymphatic drainage (MLD), compression garments, skin care, and remedial exercises. The women were taken to a 12-week therapy program once per day, 3 days per week. A home program, consisting of compression bandage exercises, skin care and walking was recommended. Absolute volume and percentage of volume of the lymphedema were compared before and after treatment. The kinesiophobia, quality of life, and home-based program were assessed before and after physiotherapy. RESULTS: Strong correlations were found between the severity of edema and fear of movement. There was a significant negative relationship among the fear of movement, quality of life, and home-based exercises program. Mean initial lymphedema volume was 925 ml, and the percentage of lymphedema was 47.1%. After decongestive physiotherapy, the lymphedema volume and percentage were 510 ml and 21.3% (P < 0.05), respectively. There was also a trend toward improvement in general well-being (P < 0.05). CONCLUSION: In upper extremity lymphedema, the use of complex physiotherapy programs (CDP) can decrease edema and fear of activity, and increase the quality of life.     

Relation Between Early Disturbance of lymphatic transport Visualized With Lymphofluoroscopy and Other Clinical Assessment Methods in Patients With Breast Cancer

IntroductionLymphedema of the upper extremity is one of the most feared complications following breast cancer treatment. Lymphofluoroscopy is a sensitive instrument for detection of lymphedema and visualization of superficial lymphatic transport, thus suitable for early detection. Early detection of lymphedema is important as it can prevent lymphedema to progress into more severe stages and minimalize impact on quality of life and medical costs.ObjectiveTo determine agreement between the presence of early disturbance of the lymphatic transport and outcome of clinical measurement tools evaluating the development of lymphedema.MethodsA prospective study was conducted in 128 breast cancer patients scheduled for breast cancer surgery. Patients were evaluated before surgery and 1, 3-, 6-, 9-, and 12-months’ post-surgery. Cohen's Kappa was used to determine agreement between presence of early disturbance in lymphatic transport and presence of pitting/increased skinfold thickness/increased Percentage Water Content ratio (PWC)/increased arm-hand volume (circumference measures and water displacement).ResultsFor pitting status (Kappa 0.23), for skinfold thickness (Kappa 0.29) and the PWC ratio (Kappa 0.21) a minimal agreement was found. The circumference measurement had a minimal agreement for 5% volume difference (Kappa 0.22) and no agreement for 3% volume difference (Kappa 0.19). Sensitivity was weak for all clinical assessments. The specificity was excellent for pitting status, skinfold thickness, PWC ratio, and for 5% volume difference. For 3% a high specificity was found.ConclusionThe clinical tools assessed in this study were not able to predict an early disturbance of the lymphatic transport seen on lymphofluoroscopy.     

3D扫描与手动方法对乳房体积测量的比较

目的:本研究采用循证医学的Meta分析比较3D扫描与手动方法测量乳房体积的可重复性.方法:检索Pubmed、Web of science、中国生物医学数据库与全文数据库(万方数据库、CNKI等)中2016年5月31日前公开发表的有关乳房体积测量的文献,根据纳入文献中三维扫描或手动方法进行归类,采用统计分析软件R对所提取的信息进行统计分析.结果:共纳入6篇相关文献,238例相关研究.3D扫描与手动方法测量乳房体积与实际乳房体积差异均无统计学意义(P>0.05),其中手动方法对乳房体积的测量与乳房的3D扫描法测得体积的异质性检验P=0.64,3D扫描与手动方法测量乳房体积结果差异无统计学意义(P>0.05).结论:3D扫描与手动方法可以准确测量乳房体积,3D扫描更高效且可重复性好,值得推广应用.     

Radiotherapy of bladder cancer: relevance of bladder volume changes in planning boost treatment

Purpose: This study aims to evaluate tumor motion with controlled changes of the bladder volume, and to assess the reproducibility of bladder (and tumor) position using a urinary catheter balloon as an immobilization device.Methods and Materials: First, three patients with tumor growths in three different bladder regions (trigone, left lateral wall, anterior wall) were evaluated. Three-dimensional CT-based reconstructed images were used to measure the displacement of the tumors when 100 cc were removed from a bladder originally filled with 170 cc of contrast. The 3D calculated boost beam arrangements and field sizes for the three tumors in the partially emptied bladders were used to simulate treatment of the same tumors in the maximally filled bladders. Dose–volume histograms were obtained. Second, verification of an ellipsoid model for bladder volume changes was undertaken in 41 patients. Third, in eight additional patients a urinary catheter balloon filled with 80-cc sterile saline solution was used in an attempt to reproduce the shape and spatial coordinates of the bladder during the boost treatment. A pair of orthogonal films with the 80-cc balloon filled with contrast material were taken at simulation and repeated twice at weekly intervals during radiotherapy. The reproducibility was quantified by sequentially calculating the common surface of the bladder images in each orthogonal view.Results: Target motion, especially in the craniocaudal axis, appeared to be more relevant for tumors arising in the bladder walls (15 mm) than in the trigone (5 mm). Underdosage (<95% of the prescribed dose to the target volume) was observed in 20, 20, and 50% (with 1 cm margins around the tumor) and in 10, 10, and 15% (with 1.5 cm margins around the tumor) of the tumors arising in the trigone, left lateral wall, and anterior wall, respectively. The ellipsoidal model was validated with a strong correlation coefficient allowing to establish a predictive model for bladder wall displacements as a function of bladder volume. In the balloon reproducibilty study, mean reproducibility factors of 0.84 (±0.06) and 0.82 (±0.07) were obtained for both anteroposterior and lateral views, respectively.Conclusions: Changes in bladder volume and shape related to bladder filling can result in clinically significant displacements of the target volume. A minimum of 2-cm margins around the target may compensate for extreme bladder volume changes during boost treatment. An ellipsoidal model for the bladder is consistent with these observations. Although an 80-cc urinary catheter balloon helped to immobilize the bladder, reproducibility was less than perfect.     

Long-Term Management of Breast Cancer-Related Lymphedema after Intensive Decongestive Physiotherapy

Background Treatment of lymphedema is based on intensive decongestive physiotherapy followed by a long-term maintenance treatment. We analyzed the factors influencing lymphedema volume during maintenance treatment. Method Prospective cohort of 537 patients with secondary arm lymphedema were recruited in a single lymphology unit and followed for 12 months. Lymphedema volume was recorded prior to and at the end of intensive treatment, and at month 6 and month 12 follow-up visits. Multivariate models were fitted to analyze the respective role of the three components of complete decongestive therapy, i.e. manual lymph drainage, low stretch bandage, and elastic sleeve, on lymphedema volume during the 1-year maintenance phase therapy. Results Mean volume of lymphedema was 1,054 ± 633 ml prior and 647 ± 351 ml after intensive decongestive physiotherapy. During the 1-year maintenance phase therapy, the mean lymphedema volume slightly increased (84 ml—95% confidence interval [CI]: 56–113). Fifty-two percent of patients had their lymphedema volume increased above 10% from their value at the end of the intensive decongestive physiotherapy treatment phase. Non-compliance to low stretch bandage and elastic sleeve were risk factors for an increased lymphedema after 1-year of maintenance treatment (RR: 1.55 [95% CI: 1.3–1.76]; P < 0.0001 and RR: 1.61 (95% CI: 1.25–1.82); P = 0.002, respectively). Non-compliance to MLD was not a risk factor (RR: 0.99 [95% CI: 0.77–1.2]; P = 0.91). Conclusion During maintenance phase after intensive decongestive physiotherapy, compliance to the use of elastic sleeve and low stretch bandage should be required to stabilize lymphedema volume.     

A simple and accurate new method for cytostatics dosimetry in isolation perfusion of the limbs based on exchangeable blood volume determination

Current methods for cytostatic dosimetry in isolation perfusion of the limbs are based on either limb tissue volume (LTV) or body weight. None of them take into account the actual blood volume intra- and extracorporal, including even the blood leakage if any, in which the pharmacokinetics take place. The present study describes a method which allows the assessment of the actual exchangeable blood volume. The latter is calculated by a formula based on three hematocrit measurements. Thirty-one cases entered the study. Exchangeable limb blood volume representing the limb vascular bed was found to average 340 +/- 148 (SD) ml for upper limb perfusion and 768 +/- 279 and 621 +/- 454 ml for iliac and femoropopliteal perfusion, respectively. There was a good correlation between exchangeable limb blood volume and limb tissue volume (LTV, r = 0.7), a poor one with body weight (r = 0.3), and no correlation at all with body surface. Melphalan dosage was calculated per ml of blood and applied at 20 to 40 micrograms/ml. Comparison between calculated dose and concentration measured by high performance liquid chromatography showed a high correlation (r = 0.963). Since there was a correlation between exchangeable limb blood volume and LTV, it was possible to derive a conversion for melphalan dosage where 13 mg/liter corresponds to 20 micrograms/ml in upper limb perfusion and 10 mg/liter corresponds to 40 micrograms/ml in lower limb perfusion. Comparison between calculated melphalan dosage based on our method and the LTV method showed a large dispersion of values in the latter (12 to 18% coefficient of variation) while the dispersion given by the body weight-based method increased 2-fold (16 to 31% coefficient of variation). It is concluded that the present dosimetry method is the most suitable up to the present for accurate prediction of cytostatic concentration in isolation perfusion.     

A new, accurate and conventional five-point method for quantitative evaluation of ascites using plain computed tomography in cancer patients

BACKGROUND: To assess the exact response of the malignant ascites to the treatment, the objective measurement of the volume of ascites is essential. We have developed a simple method to measure the volume of ascites by using standard abdomino-pelvic computed tomography (CT). The aim of the study is to validate the accuracy of the measurements by comparing them with the standard volume calculation by using 3D-CT. METHODS: Twelve consecutive patients with cancer who had measurable ascites underwent 15 helical CT examinations. On conventional CT images, the thickness of ascites in centimeters was measured in three planes such as the bilateral subphrenic space (A and B), the bilateral paracolic space (C and D) and the pre-bladder space (E), and the average thickness: (A + B + C + D + E)/5 was then multiplied by the area of standard abdominal cavity in the anterior projection, that was assumed to be 1000 cm(2), to yield the volume of ascites: (A + B + C + D + E) x 200 (ml). The volume of ascites was compared with the exact volume, that was obtained from 3D-CT with the volume rendering method. RESULTS: The volume of ascites measured by the present method and the volume rendering method ranged from 140 to 4040 ml and from 86 to 4279 ml, respectively. The correlation was statistically significant with a correlation coefficient of 0.956 (P < 0.01) using the Spearman's rank correlation. In 13 examinations with the exact volume > or =300 ml, the average ratio of the absolute difference in the volume was 12.9 +/- 13.9% as compared with 62.8 and 162.0% in two examinations with the exact volume < 300 ml. CONCLUSION: The preliminary study indicated that the present five-point method using a conventional CT was accurate in patients with the volume of ascites > or =300 ml. Because this procedure is simple and easy to perform, it should be feasible in many hospitals for the follow-up of ascites after treatment.     

Online volume rendering of incrementally accumulated LSCEM images for superficial oral cancer detection

Laser scanning confocal endomicroscope (LSCEM) has emerged as an imaging modality which provides non-invasive, in vivo imaging of biological tissue on a microscopic scale. Scientific visualizations for LSCEM datasets captured by current imaging systems require these datasets to be fully acquired and brought to a separate rendering machine. To extend the features and capabilities of this modality, we propose a system which is capable of performing realtime visualization of LSCEM datasets. Using field-programmable gate arrays, our system performs three tasks in parallel: (1) automated control of dataset acquisition; (2) imaging-rendering system synchronization; and (3) realtime volume rendering of dynamic datasets. Through fusion of LSCEM imaging and volume rendering processes, acquired datasets can be visualized in realtime to provide an immediate perception of the image quality and biological conditions of the subject, further assisting in realtime cancer diagnosis. Subsequently, the imaging procedure can be improved for more accurate diagnosis and reduce the need for repeating the process due to unsatisfactory datasets.     

Effect of photodynamic treatment of human endothelial cells on cell volume and cell viability

Photodynamic therapy (PDT) has yielded promising results in the treatment of malignant tumors. However, the mechanisms leading to tumor destruction during PDT are still not completely understood. In addition to effects on the microcirculation, damage to cellular structures has been observed following exposure of cells to PDT. A phenomenon preceding these events might possibly be cell swelling. We therefore studied the influence of treatment with Photofrin(R) (PF) and laser light on volume changes and cell viability of endothelial cells. Endothelial cells were obtained from human umbilical cord veins (HUVEC) by an adaption of the method of Maruyama. After subcultivation the cells were harvested and transferred as a cell suspension into a specially designed incubation chamber. Cells received either PF in concentrations of 1.5 or 3.0 mu g/ml and laser illumination 60 min post incubation (630 nm; 40 mW/cm(2), 4 Joule), PF alone, or laser treatment only. Following start of PF incubation and after phototreatment cell samples were taken for volume measurements using flow cytometry, and for studies of cellular morphology using scanning electron microscopy. Simultaneously, cell viability was monitored by the trypan blue exclusion test and the colorimetric MTT assay. Both control groups, HUVEC receiving PF or laser treatment alone, revealed constant cell volumes and cell viability during the entire course of the experiment. After PDT (60 min post-incubation) with 1.5 and 3.0 mu g PF/ml cell volume of HUVEC was increased at 15 min to 122%+/-6% and 140%+/-10% of baseline (100%), at 60 min to 152%+/-9% and 134%+/-18%, respectively (p<0.01). The number of viable cells was significantly reduced of samples treated with 1.5 and 3.0 mu g PF/ml at 15 min after PDT to 81%+/-3% and 76%+/-10% of baseline (100%), at 60 min after PDT to 32%+/-14% and 20%+/-15%, respectively (p<0.01). Scanning electron microscopy of cells exposed to PDT following 60 min incubation with Photofrin (3.0 mu g/ml) revealed significant cell damage. At the highest PF concentration HUVEC showed loss of microvilli and formation of blebs on the cellular surface. Our study demonstrates that PDT induces a significant increase in endothelial cell volume and a loss of cell viability. We suggest that swelling and damage of endothelial cells following PDT is a primary event finally contributing to cessation of blood flow and subsequent necrosis of tumors.     

Effectiveness of the treatment-phase of two-phase complex decongestive physiotherapy for the treatment of extremity lymphedema

Background Complex decongestive physiotherapy (CDP) consists of a two-phase treatment program and is the international standard therapy for lymphedema. However, this therapy is not performed at most hospitals in Japan. Methods The subjects of the present study were 82 Japanese women with lymphedema of an extremity (median age, 64 years; range, 40–86 years). The volume of the affected extremity was compared before and after therapy, and the duration of the CDP treatment phase and rate of edema reduction were ascertained. The associations between the effect of CDP and duration of lymphedema, operative procedure, and radiotherapy were also investigated. Results For patients with upper-extremity lymphedema, the median duration of the CDP treatment phase was 6 treatment days (range, 3–26 days), median reduction of edema volume was 328.7 ml (range, 76.6–1258.0 ml; P = 0.0014), and median rate of edema reduction was 58.9% (range, 42.7%–97.1%). For patients with lower-extremity lymphedema, the median duration of the CDP treatment phase was 10 treatment days (range, 2–35 days), median reduction of edema volume was 1573.7 ml (range, 293.9–3471.1 ml; P < 0.0001), and median rate of edema reduction was 73.4% (range, 29.2%–117.3%). Although no correlation was seen between duration of lymphedema and duration of the CDP treatment phase or rate of edema reduction, the degree of lymph node dissection tended to influence rate of edema reduction in patients with lower-extremity lymphedema. Conclusion In a study of Japanese women with lymphedema, CDP comprising a two-phase treatment program was clearly effective.