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A Rijnders

Publications and source records attributed to A Rijnders.

At least 19 recordsLinked to original sources

The relation of CT-determined tumor parameters and local and regional outcome of tonsillar cancer after definitive radiation treatment.

PURPOSE: To investigate the value of CT-derived tumor parameters as predictor of local and regional outcome of tonsillar squamous cell carcinoma treated by definitive radiation therapy. METHODS AND MATERIALS: The pretreatment CT studies of 112 patients with tonsillar squamous cell carcinoma were reviewed. After redigitizing the films, primary and nodal tumor volume was calculated with the summation-of-areas technique. The nodal CT aspect was graded using a 3-point scale (homogenous, inhomogeneous, and necrotic). Mean follow-up time was 33 months. Actuarial statistical analysis of local and regional outcome was done for each of the covariates; multivariate analysis was performed using Cox's proportional hazards model. RESULTS: In the actuarial analysis, CT-determined primary tumor volume was significantly correlated with local recurrence rate (p < 0.05) when all patients were considered, but primary tumor volume did not predict local control within the T2, T3, and T4 category. CT-determined nodal volume was significantly related to regional outcome (p < 0.01), but nodal density was not. Total tumor volume was not significantly related to locoregional outcome (p = 0.1). In the multivariate analysis, the T and N categories were the independent predictors of local and regional outcomes, respectively. CONCLUSION: Compared to other head-and-neck sites, primary and nodal tumor volume have only marginal predictive value regarding local and regional outcome after radiation therapy in tonsillar cancer.

Adult↗

In vivo antitumor effect of vascular targeting combined with either ionizing radiation or anti-angiogenesis treatment.

PURPOSE: Interference with the tumor blood vessels through anti-angiogenesis or vascular targeting can indirectly suppress tumor growth. Vascular targeting of solid tumors, using tubulin-compromising agents, seems a promising and selective novel treatment. We aimed to evaluate the potential (hypothesis-based) benefit from combinations of vascular targeting using combretastatin A-4 phosphate (combreAp) with either ionizing radiation or anti-angiogenesis. METHODS AND MATERIALS: Rhabdomyosarcoma tumor pieces were inplanted subcutaneously (s.c.) in the lower flank region of syngeneic adult WAG/Rij rats. Tumors were grown until different sizes and stratified for the various treatment groups: small (1-3 cm3), medium (3.1-7 cm3), and large (7.1-14 cm3). CombreAp was injected i.p.; injections of TNP-470 were s.c. in the neck area. Localized single-dose (8 Gy) irradiations of tumors were done under Nembutal anesthesia, always 1 day before a single combreAp (25 mg/kg) injection. The TNP-470 treatment (3 times 30 mg/kg in 1 week) started 1 day after a double (8 days interval between both) combreAp administration. Tumor responses were evaluated by the growth delay assay, and statistical significance of tumor growth change was computed. RESULTS: Large tumors responded better to combreAp treatment given alone than did the smaller ones, confirming our previous data with this tumor model. Combining irradiation with combreAp also resulted in a tumor size-dependent growth delay. With small and medium tumor volumes, a similar response was measured after the combination treatment when compared with irradiation only. Large tumors, however, showed a strong (at least additive) increase of the growth delay with the combined therapy; the difference in tumor growth between the two treatment groups was very significant (p < 0.0001). m When TNP-470 was combined with combreAp, no significant lengthening of the growth delay, irrespective of the tumor size, was present with the applied schedule. CONCLUSION: The current data show a significant advantage in the combination of combreAp with irradiation in rhabdomyosarcomas having a large size (7-14 cm3) at treatment. Such a benefit in tumor response was not observed with the smaller tumors, seemingly because irradiation as such was very effective. No significant gain in growth delay for any tumor size was observed when TNP-470, showing efficacy on its own specifically with tumors measuring <7 cm3, was added to the combreAp treatment. This presumably reflects only little angiogenesis during the first week of rhabdomyosarcoma regrowth after the combreAp treatment.

Angiogenesis Inhibitors↗

Quality control in interstitial brachytherapy of the breast using pulsed dose rate: treatment planning and dose delivery with an Ir-192 afterloading system.

BACKGROUND AND PURPOSE: In the Radiotherapy Department of Leuven, about 20% of all breast cancer patients treated with breast conserving surgery and external radiotherapy receive an additional boost with pulsed dose rate (PDR) Ir-192 brachytherapy. An investigation was performed to assess the accuracy of the delivered PDR brachytherapy treatment. Secondly, the feasibility of in vivo measurements during PDR dose delivery was investigated. MATERIALS AND METHODS: Two phantoms are manufactured to mimic a breast, one for thermoluminescent dosimetry (TLD) measurements, and one for dosimetry using radiochromic films. The TLD phantom allows measurements at 34 dose points in three planes including the basal dose points. The film phantom is designed in such a way that films can be positioned in a plane parallel and orthogonal to the needles. RESULTS: The dose distributions calculated with the TPS are in good agreement with both TLD and radiochromic film measurements (average deviations of point doses <+/-5%). However, close to the interface tissue-air the dose is overestimated by the TPS since it neglects the finite size of a breast and the associated lack of backscatter (average deviations of point doses -14%). CONCLUSION: Most deviations between measured and calculated doses, are in the order of magnitude of the uncertainty associated with the source strength specification, except for the point doses measured close to the skin. In vivo dosimetry during PDR brachytherapy treatment was found to be a valuable procedure to detect large errors, e.g. errors caused by an incorrect data transfer.

Brachytherapy↗

Determination of the accuracy of implant reconstruction and dose delivery in brachytherapy in The Netherlands and Belgium.

PURPOSE: To gain insight into the accuracy of brachytherapy treatments, the accuracy of implant reconstruction and dose delivery was investigated in 33 radiotherapy institutions in The Netherlands and Belgium. MATERIALS AND METHODS: The accuracy of the implant reconstruction method was determined using a cubic phantom containing 25 spheres at well-known positions. Reconstruction measurements were obtained on 41 brachytherapy localizers, 33 of which were simulators. The reconstructed distances between the spheres were compared with the true distances. The accuracy of the dose delivery was determined for high dose rate (HDR), pulsed dose rate (PDR) and low dose rate (LDR) afterloading systems using a polymethyl methacrylate cylindrical phantom containing a NE 2571 ionization chamber in its centre. The institutions were asked to deliver a prescribed dose at the centre of the phantom. The measured dose was compared with the prescribed dose. RESULTS: The average reconstruction accuracy was -0.07 mm (+/-0.4 mm, 1 SD) for 41 localizers. The average deviation of the measured dose from the prescribed dose was +0.9% (+/-1.3%, 1 SD) for 21 HDR afterloading systems, +1.0% (+/-2.3%, 1 SD) for 12 PDR afterloaders, and +1.8% (+/-2.5%, 1 SD) for 15 LDR afterloaders. CONCLUSIONS: This comparison showed a good accuracy of brachytherapy implant reconstruction and dose delivery in The Netherlands and Belgium.

Belgium↗

The utility of SPECT in determining the relationship between radiation dose and salivary gland dysfunction after radiotherapy.

Salivary gland scintigraphy (SGS) is used to depict salivary gland dysfunction after radiotherapy (RT). The aim of this study was to investigate the utility of SGS combined with single photon emission computed tomography (SPECT). Twenty-one patients with a carcinoma of head and neck underwent SGS before and 1 month after RT. After injection of 370 MBq 99Tcm-pertechnetate, a biplanar dynamic acquisition (12 x 1 min) was started, followed by a SPECT acquisition during 4 min. Carbachol was then injected and a second dynamic study (16 x 1 min) was performed, again followed by a SPECT acquisition. The salivary excretion fraction (SEF) was calculated both from the geometric mean planar image for each parotid and from the SPECT data for each transverse plane through the parotids. The RT-induced changes in the SEF (dSEF) were correlated with the mean radiation dose calculated using tomography-based dosimetry. The mean radiation dose to the parotids was 44 Gy (range 4.4-68.1 Gy). The mean range of the variation in radiation dose to the transverse slices within the parotids of a patient was 24 Gy (range 6.2-51.9 Gy). Considering all transverse planes through the parotids in all patients, a linear correlation was found between the dSEF calculated using SGS-SPECT and the radiation dose (r=0.45, P=0.0001). Thirteen patients had a variation in radiation dose within the parotids of more than 20 Gy. In nine of these a significant intra-individual correlation between radiation dose and the dSEF of the transverse parotid slices was found (r range 0.55-0.97; P value range 0.037-0.0001). In conclusion, SGS-SPECT can be used for monitoring radiation-induced parotid gland dysfunction. It offers the unique possibility for the assessment of intra-individual dose-dysfunction curves in patients with large variations in the radiation dose within the parotids.

Adult↗

Improvement of Clostridium tumour targeting vectors evaluated in rat rhabdomyosarcomas.

Previous studies have demonstrated the feasibility of using apathogenic clostridia as a promising strategy for hypoxia-specific tumour targeting. The present study shows that the use of the vascular targeting compound combretastatin A-4 phosphate could significantly (P<0.001) increase the number of Clostridium vegetative cells in rat rhabdomyosarcomas with sizes between 0.2 cm(2) and 3 cm(2). Furthermore, this study showed that administration of metronidazole for a 9-day period was sufficient to eliminate systemically administered Clostridium from the tumour. Moreover, previous Clostridium spore administration did not effect tumour colonisation, regardless of the immune response status of the host.

Animals↗

Radiotherapy for PSA recurrence after radical prostatectomy.

OBJECTIVES: The treatment of patients presenting with an isolated PSA recurrence after radical prostatectomy (RP) remains controversial. The present study aims at assessing the results of salvage radiotherapy (RT), to define prognostic factors and to identify subgroups of patients most suitable for RT with curative intent. MATERIALS AND METHODS: A retrospective study was performed of 53 patients, diagnosed with a rising PSA after RP, and treated with RT to the prostate bed, between July 1992 and July 1998. RESULTS: On univariate analysis, significant determinants to obtain and maintain a nondetectable PSA (< 0.02 ng/ml) were Gleason grade (< or = III vs. < or = IV), pre-RT PSA, considered as categorical or continuous variable, and pathological stage, pT (2 vs. 3). Pre-RP PSA (< or = 10 vs. >10), time interval between surgery and moment of rising PSA and pathological section margin status were not significant. On multivariate analysis, only Gleason grade and pre-RT PSA remained significant. For the patient group with a Gleason grade < or = III the PSA-free survival at 3 years was 75% (+/- 11%) compared to 27% (+/- 9%) for the patients with a Gleason grade > or = IV (p = 0.002). Pre-RT PSA significantly influenced PSA-free survival in the first group, but not in the latter. CONCLUSION: From the group of RP patients with rising PSA following a postsurgery PSA-free period, subgroups can be defined with a distinctly different probability of obtaining and maintaining nondetectable PSA levels after salvage RT.

Aged↗

Palliative radiotherapy practice within Western European countries: impact of the radiotherapy financing system?

PURPOSE: To analyze the reimbursement modalities for radiotherapy in the different Western European countries, as well as to investigate if these differences have an impact on the palliative radiotherapy practice for bone metastases. MATERIALS AND METHODS: A questionnaire was sent to 565 radiotherapy centres included in the 1997 ESTRO directory. In this questionnaire the reimbursement strategy applied in the different centres was assessed, with respect to the use of a budget (departmental or hospital budget), case payment and/or fee-for-service reimbursement. The differences were analyzed according to country and to type and size of the radiotherapy centre. RESULTS: A total of 170 centres (86% of the responders) returned the questionnaire. Most frequent is budget reimbursement: some form of budget reimbursement is found in 69% of the centres, whereas 46% of the centres are partly reimbursed through fee-for-service and 35% through case payment. The larger the department, the more frequent the reimbursement through a budget or a case payment system and the less the importance of fee-for-service reimbursement (chi(2): P=0.0012; logit: P=0.0055). Whereas private centres are almost equally reimbursed by fee-for-service financing as by budget or case payment, radiotherapy departments in university hospitals receive the largest part of their financial resources through a budget or by case payment (83%) (chi(2): P=0.002; logit: P=0.0073). A correlation between the country and the radiotherapy reimbursement system was also demonstrated (P=0.002), radiotherapy centres in Spain, the Netherlands and the United Kingdom being almost entirely reimbursed through a budget and/or case payment and centres in Germany and Switzerland mostly through a fee-for-service system. In budget and case payment financing lower total number of fractions and lower total dose (chi(2): P=0.003; logit: P=0.0120) as well as less shielding blocks (chi(2): P=0.003; logit: P=0.0066) are used. A same tendency is found for the use of isodose calculations and field set-up, but without being statistically significant (P=0.264 and P=0.061 res.). The type of the centre and the reimbursement modality influence the fractionation regimen independently (P=0.0274). This is not the case for the centre size and the reimbursement, which were found to exert correlated effects on the fractionation schedule (P=0.1042). CONCLUSION: Reimbursement systems seem to influence radiotherapy practice. One should therefore aim to develop reimbursement criteria that pursue to deliver, not only the best qualitative, but also the most cost-effective treatments to the patients.

Bone Neoplasms↗

Differences in palliative radiotherapy for bone metastases within Western European countries.

PURPOSE: To evaluate the differences in palliative radiotherapy for painful bone metastases amongst different Western European countries. MATERIALS AND METHODS: A questionnaire was sent to 565 radiotherapy centres in 19 Western European countries, based on the 1997 ESTRO directory. In this questionnaire the current local palliative radiotherapy practice for bone metastases was assessed in terms of total dose, fractionation, treatment complexity (use of shielding blocks, frequency of isodose calculations, field set-up) and type of machine used. The differences were analyzed according to the country and to the type and size of radiotherapy centre. RESULTS: A total of 205 centres (36%) returned the questionnaire, of which 198 could be further analyzed. The most frequently used antalgic fractionation schedule is 30 Gy in ten daily fractions of 3 Gy (50%), single fractions and conventional 2 Gy fractions being used in a minority of the centres (respectively, 11 and 9%). Most antalgic treatments are performed on a linear accelerator (67% of the centres uses linear accelerators) and 64% of the centres predominantly uses a two-field set-up. The majority of the centres uses shielding blocks and performs isodose calculations in less than 50% of the patients, (respectively, 88 and 81%). There is a correlation between the centre size and the palliative irradiation practice, the largest centres using more hypofractionation (chi(2): P=0.001; logit: P=0. 0003) and a less complex treatment set up as expressed by the use of isodose calculations (chi(2): P=0.027; logit: P=0.0161). There is also a tendency to use less shielding blocks (P=0.177). The same goes for university centres as compared with private centres: university centres use shorter fractionation schedules (chi(2): P=0. 008; logit: P=0.0094), less isodoses (chi(2): P=0.010; logit: P=0. 0115) and somewhat less shielding blocks (P=0.151). Amongst the analyzed countries different tendencies in fractionation (P=0.001) and treatment complexity are observed (use of isodoses: P=0.014, use of shielding blocks: P=0.001). CONCLUSION: These data suggest that beside work-load and clinical evidence, country-related factors such as tradition and habits, past teaching, the national organization of health care and reimbursement criteria may influence the local practice.

Bone Neoplasms↗

Long term survival of a patient with malignant pleural mesothelioma as a late complication of radiotherapy for Hodgkin's disease treated with 90yttrium-silicate.

A case of malignant pleural mesothelioma (PM) 24 years after thoracic radiotherapy for Hodgkin's disease is presented. As primary treatment and to relieve symptoms of dyspnea secondary to pleural effusion a thoracic drain was installed, followed by intracavitary radiation therapy with 90yttrium-silicate. Minor complaints of fever and a dry cough as a side-effect of this treatment were effectively treated with prednisone during 2 weeks. The patient remains in a good clinical condition now 6 years after diagnosis. Considering the few therapeutic options the use of 90yttrium-silicate intrapleural installation could be propagated as a safe and effective antitumour treatment for a selected group of patients with malignant PM.

Hodgkin Disease↗

Value of computed tomography as outcome predictor of supraglottic squamous cell carcinoma treated by definitive radiation therapy.

PURPOSE: To investigate the value of several CT-derived tumor parameters as predictors of local outcome of supraglottic squamous cell carcinoma treated by definitive radiation therapy. METHODS AND MATERIALS: The pretreatment CT studies of 103 patients with supraglottic squamous cell carcinoma were reviewed for tumoral involvement of specific laryngeal anatomic subsites and extralaryngeal tumor spread. After redigitizing the films, tumor volume was calculated with the summation-of-areas technique. Mean follow-up time was 3.4 years. Actuarial statistical analysis of local and locoregional outcome was done for each of the covariates; multivariate analysis was performed using Cox's proportional hazards model. RESULTS: In the actuarial analysis CT-determined primary tumor volume was significantly correlated with local recurrence rate (p < 0.001). Degree of involvement of the paraglottic space at the level of the true vocal cord (p < 0.05) and subglottic extension (p < 0.001) were also significantly correlated with local recurrence rate. In the multivariate analysis, only degree of involvement of the preepiglottic space (p < 0.01) and subglottic extension (p < 0.01) were found to be independent predictors of local recurrence. Total tumor volume was the strongest independent predictor of locoregional failure (p < 0.01). CONCLUSIONS: CT-determined tumor parameters are strong predictors of local and locoregional outcome of supraglottic carcinoma treated by definitive irradiation.

Adult↗

Predicting the local outcome of glottic squamous cell carcinoma after definitive radiation therapy: value of computed tomography-determined tumour parameters.

BACKGROUND AND PURPOSE: The T-classification has shortcomings in the prediction of local outcome of glottic squamous cell carcinoma (SCC) treated by definitive radiation therapy. In this regard, the value of several CT-derived tumour parameters as predictors of local outcome was investigated. MATERIALS AND METHODS: The pretreatment CT studies of 119 patients with glottic SCC (T1, n=61; T2, n=40; T3, n=14; T4, n=4) treated with curative intent by radiation therapy were reviewed for tumoral involvement of specific laryngeal anatomic subsites (including laryngeal cartilages). Tumour volume was calculated with the summation-of-areas technique. Actuarial (life-table) statistical analysis was done for each of the covariates; multivariate analysis was performed using the Cox proportional hazards model. RESULTS: In the actuarial analysis tumour volume was significantly correlated with local recurrence rate (P=0.0062). Involvement of the cricoid cartilage (P=0.0052), anterior commissure (P=0.0203), subglottis (P=0.0481) and preepiglottic space (P=0.0134) and degree of involvement of the true vocal cord (P=0.0441) and paraglottic space at the level of the true vocal cord (P=0.0002) were also significantly correlated with local recurrence rate. In the multivariate analysis, only degree of involvement of the paraglottic space (at the level of the true vocal cord) (P=0.0001) and preepiglottic space (P=0.02) were found to be independent predictors of local recurrence. The T-category was significantly correlated with local outcome in the actuarial analysis (P=0.0001), but not in the multivariate analysis (P=0.5915). CONCLUSIONS: Several CT-derived parameters are powerful predictors of local outcome in glottic cancer treated with radiation therapy; some of these parameters are stronger linked to the local control rate than the T-classification.

Adult↗

The time course of development of late side effects after irradiation of the prostate with multiple fractions per day.

BACKGROUND AND PURPOSE: A group of patients with prostate cancer was irradiated in the early 1980s with a TID schedule, resulting in a very high frequency of side effects. The time course of development of severe late complications was evaluated. MATERIALS AND METHODS: We retrospectively reviewed the records of 91 patients with prostate cancer, irradiated on a linear accelerator or a cobalt unit between 1980 and 1983. They received a split-course irradiation with multiple fractions per day (MFD) up to a nominal dose of 60 Gy. The rate of development of severe late urological and gastrointestinal complications, grade 3 or more according to the RTOG scoring system, was analysed. RESULTS: The 5-year actuarial incidence of urological complications was 51%. After a lag time of a few months, patients develop "first events' at a nearly constant rate of 10% for 5 years after treatment. Subsequent events ("all events') seem to continue to appear even after 5 years. The actuarial incidence at 5 years of gastrointestinal complications was 14%, with no new events developing later than 3 years after treatment. CONCLUSIONS: The irradiation schedule used resulted in an unacceptable high incidence of late side effects, probably due to incomplete repair between fractions. MFD fractions to the pelvis should be avoided, unless sufficient time in between fractions can be allowed. Moreover, the fact that after this treatment schedule with very pronounced biological effects, new severe complications continued to develop up to 5 years after therapy, indicates that sufficiently long follow-up time has to be respected when investigating new radiation techniques for pelvic tumours.

Aged↗

Does tumor control decrease by prolonging overall treatment time or interrupting treatment in laryngeal cancer?

PURPOSE: To evaluate treatment results of radiotherapy in laryngeal cancer and to retrospectively investigate the influence of treatment interruptions on local control rates. A multivariate analysis was performed to investigate the role of overall treatment time on local control rates. MATERIAL AND METHODS: From 1962 to end 1986, 864 patients with cancer of the larynx were treated with primary radiotherapy, with a variation of doses and treatment times. In 352 patients a systematic interruption of 2 weeks was done after 50 Gy (split-course). Local control rates were calculated by the actuarial method. A multivariate analysis was subsequently performed in order to identify independent variables influencing local control rates. RESULTS: The univariate analysis showed that in patients treated with a split-course schedule, local control rates were significantly lower in glottic cancer (p < 0.001), with differences of 7% in T1 (p = 0.05) and 11% in T2 (p = 0.11). In node-negative supraglottic cancer a difference of 10% (p = 0.16) was observed. The multivariate analysis showed the following factors to significantly influence local control: site, total dose, total treatment time, T and N stage. Split-course treatment was not an independently significant factor, probably caused by time being a stronger factor. In subgroup analysis, the effect of total treatment time remained statistically significant in T2 glottic cancer. CONCLUSION: A significant negative influence of treatment interruption was seen in glottic cancer, and a trend toward significance in node-negative supraglottic cancer in univariate analysis. A multivariate analysis showed a negative influence of prolonging treatment time in the total patient group. The effect remained significant in T2 glottic cancer in subsequent subgroup analysis, possibly due to the fact that there is little variation in tumour volume in this group. In larger tumours, where there is substantial variation in tumour volume and a higher probability of heterogeneity in radiosensitivity, the effect of dose-time variations could be more difficult to discern.

Female↗

Breast conserving treatment of Paget's disease.

Between 1971 and 1984, 13 patients with histologically proven Paget's disease were treated conservatively with radiotherapy only. The disease was clinically confined to the nipple or surrounding skin, without signs of an underlying tumor. With a mean follow-up of 58.6 months (ranging between 15 and 118 months), and a median follow up of 52 months, no recurrences locally or at distance were seen. Therefore in these selected cases a mastectomy could be avoided. The results with this breast conserving management suggest a place for radiotherapy in the treatment of Paget's disease limited to the nipple.

Aged↗

Cosmetic evaluation of breast conserving treatment for mammary cancer. 2. A quantitative analysis of the influence of radiation dose, fractionation schedules and surgical treatment techniques on cosmetic results.

The effects of surgical treatment techniques, radiation doses and fraction sizes on cosmetic outcome were analysed in a population of 161 patients with stage I and II breast cancer treated with breast conserving surgery and a wide range of radiotherapy doses. In 142 patients also quantitative measurements of nipple position asymmetries and breast contour retraction were carried out. The scoring and measurement results were analysed using a multivariate model to assess the relative importance of the various factors involved. In this material radiation dose to the breast was the most significant parameter correlated with cosmetic outcome (p = 0.0001). Radiation doses higher than 75 Gy in 37 fractions led to very poor results in more than 30% of patients. For the quantitative measurements of radiation fibrosis, a dose-response curve could be demonstrated over a dose range of 40 to 86 Gy in fraction sizes of 2 Gy. Above 50 Gy, increases in dose of 1 Gy correlated with an average displacement of nipple and breast contour of 1 mm, in upward direction and of 0.75 mm to the median. An increased amount of fibrosis was observed when part of the treatment was given in larger fraction sizes (4-6 Gy). Plotting the data against dose equivalent TE values, an alpha/beta value of 2.5 Gy could be estimated for the development of late fibrosis. Other treatment factors whose influence on cosmetic outcome could be identified and quantified were the differences in surgical techniques for the removal of the primary tumor (tumorectomy vs. segmentectomy, p = 0.05) and for the axillary clearance ("en bloc" dissection vs. separate incisions, p = 0.018). Also technical aspects of the radiotherapy on the regional lymph nodes, sometimes leading to matchline fibrosis, proved to be important (p = 0.0075). Finally, a number of tumor-related factors were assessed in order to take their relative importance into account, if necessary, when studying therapy factors. While tumor stage had only a limited impact in the range of tumors included in this study, the localisation of the tumor significantly influenced cosmetic outcome with worse results for inferior and medial localisations. While quantitative measurements were not correlated with all the factors identified for poor cosmesis, their great value is to quantify the radiation-induced fibrosis as well as the effects of different surgical techniques on nipple retraction.

Breast↗