Ten daily fractions for partial breast irradiation. Long‐term results of a prospective phase II trial

Partial breast irradiation (PBI) is an effective adjuvant treatment after breast conservative surgery for selected early‐stage breast cancer patients. However, the best fractionation scheme is not well defined. Hereby, we report the 5‐year clinical outcome and toxicity of a phase II prospective study of a novel regimen to deliver PBI, which consists in 40 Gy delivered in 10 daily fractions. Patients with early‐stage (pT1‐pT2, pN0‐pN1a, M0) invasive breast cancer were enrolled after conservative surgery. The minimum age at diagnosis was 60 years old. PBI was delivered with 3D‐conformal radiotherapy technique with a total dose of 40 Gy, fractionated in 10 daily fractions (4 Gy/fraction). Eighty patients were enrolled. The median follow‐up was 67 months. Five‐year local control (LC), disease‐free survival (DFS), and overall survival (OS) were 95%, 91%, and 96%, respectively. Grade I and II subcutaneous fibrosis were documented in 23% and 5% of cases. No grade III late toxicity was observed. PBI delivered in 40 Gy in 10 daily fractions provided good clinical results and was a valid radiotherapy option for early‐stage breast cancer patients.     

Accelerated partial breast irradiation using 3D conformal radiotherapy: Toxicity and cosmetic outcome

PurposeThe aim of this paper is to analyze the incidence of acute and late toxicity and cosmetic outcome in breast cancer patients submitted to breast conserving surgery and three-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI).Methods and materials84 patients were treated with 3D-CRT for APBI. This technique was assessed in patients with low risk stage I breast cancer enrolled from September 2005 to July 2011. The prescribed dose was 34/38.5 Gy delivered in 10 fractions twice daily over 5 consecutive days. Four to five no-coplanar 6 MV beams were used. In all CT scans Gross Tumor Volume (GTV) was defined around the surgical clips. A 1.5 cm margin was added by defining a Clinical Target Volume (CTV). A margin of 1 cm was added to CTV to define the planning target volume (PTV). The dose–volume constraints were followed in accordance with the NSABP/RTOG protocol. Late toxicity was evaluated according to the RTOG grading schema. The cosmetic assessment was performed using the Harvard scale.ResultsMedian patient age was 66 years (range 51–87). Median follow-up was 36.5 months (range 13–83). The overall incidence of acute skin toxicities was 46.4% for grade 1 and 1% for grade 2. The incidence of late toxicity was 16.7% for grade 1, 2.4% for grade 2 and 3.6% for grade 3. No grade 4 toxicity was observed. The most pronounced grade 2 late toxicity was telangiectasia, developed in three patients. Cosmetics results were excellent for 52%, good for 42%, fair for 5% and poor for 1% of the patients. There was no statistical correlation between toxicity rates and prescribed doses (p = 0.33) or irradiated volume (p = 0.45).ConclusionsAPBI using 3D-CRT is technically feasible with very low acute and late toxicity. Long-term results are needed to assess its efficacy in reducing the incidence of breast relapse.     

Breast cancer following breast prosthesis and irradiation in childhood]

The authors report a case of breast cancer developing 7 years after insertion of a breast prosthesis. This patient was 45 years old at the time of this discovery and had received low dose radiation during childhood for a haemolymphangioma of the homolateral axillary region. The possible factors predisposing development of cancer are discussed: haemolymphangioma, low dose axillary irradiation during childhood, peri-prosthetic fibrous capsule. These various points are examined in the light of data from the literature. The conclusions recall the necessity for clinical and radiological follow-up of breast prostheses, preferably performed by a plastic surgeon.     

Plastic and reconstructive surgery in Uganda – 10 years experience

We describe our experience of working in plastic and reconstructive surgery in Uganda over the last 10 years. There is a high burden of disease, a health system that is under resourced, and few qualified physicians to provide healthcare for a principally rural population. Training the physicians of the future is essential. Prevention and early wound management needs to be emphasized for traumatic injuries including burns. Subsidized up-country visits by trained specialists with the appropriate equipment are required to provide a service for the rural poor. There appears to be a high mortality rate in babies with unrepaired cleft palate, probably due to feeding difficulties in an environment where intercurrent illness is common. We now offer nutritional support with early combined cleft lip and palate repair in these babies, a practice that has a high success rate and may be suited to other specialist units in the developing world.     

Acute toxicity and health-related quality of life after accelerated whole breast irradiation in 5 fractions with simultaneous integrated boost

IntroductionAcceleration of radiotherapy in 5 fractions for breast cancer can reduce the burden of treatment. We report on acute toxicity after whole-breast irradiation with a simultaneous integrated boost in 5 fractions over 10–12 days.Material and methodsAcute toxicity and health-related quality of life (HRQoL) of 200 patients, randomized between a 15- or 5-fractions schedule, were collected, using the CTCAE toxicity scoring system, the Multidimensional Fatigue Inventory, EORTC QLQ-C30 and BR23 and the BREAST-Q questionnaire. The prescribed dose to the breast was either 1512.67 Gy (40.05 Gy) or 515.7 Gy (28.5 Gy). 90% of patients received a SIB to a cumulative dose of 46.8 Gy (1513.12 Gy) or 31 Gy (516.2 Gy).ResultsPhysician-assessed toxicity was lower for the 5-fractions group. A significant difference was observed for breast pain (p = 0.002), fatigue (p < 0.0001), breast edema (p = 0.001) and dermatitis (p = 0.003). Patients treated in 5 fractions reported better mean HRQoL scores for breast symptoms (p = 0.001) and physical well-being (p = 0.001). A clinically important deterioration in HRQoL of 10 points or more was also less frequently observed in the latter group for physical functioning (p = 0.0005), social functioning (p = 0.0007), fatigue (p = 0.003), breast symptoms (p = 0.0002) and physical well-being (p = 0.002).ConclusionIn this single institute study, acute toxicity of accelerated breast radiotherapy in 5 fractions over 10–12 days seems to compare favourably to hypofractionated breast radiotherapy in 15 fractions. Less breast edema, dermatitis, desquamation, breast pain and fatigue are seen. Social and physical functioning are also less disturbed and patients have a better future perspective.     

MAP3K10在胰腺癌中的表达及其意义

目的:探讨丝裂原活化蛋白3激酶10（MAP3K10）在胰腺癌中的表达。
方法:应用免疫组织化学染色技术，Western blot及定量RT-PCR检测MAP3K10在胰腺癌及癌旁组织中的表达。
结果:(1)免疫组化染色阳性细胞计数显示MAP3K10在胰腺癌组织中的阳性细胞数（100%呈强阳性）明显多于癌旁组织（仅25%呈弱阳性）(P＜0.05)；(2)Western blot检测显示，在91.7%的胰腺癌组织中MPA3K10蛋白的表达量高于癌旁组织；(3)qRT-PCR检测显示，MAP3K10mRNA在胰腺癌及癌旁组织中均有表达，但前者的表达水平明显高于后者（P＜0.01）。
结论:MAP3K10在胰腺癌中存在异常激活，可能在胰腺癌的发生发展中起重要作用，有望成为胰腺癌新的治疗靶点

     

Breast conserving therapy with accelerated partial breast versus external beam whole breast irradiation: comparison of imaging sequela and complications in a matched population

Our purpose was to evaluate and compare the imaging sequela and complications of accelerated partial breast irradiation (APBI) with those occurring in patients treated with standard external beam therapy. Patient selection included those who met the criteria for possible ABPI: age 45 or older; cancer stage T1N0M0 or ductal carcinoma in situ 3 cm or less, and negative surgical margins. One hundred and ninety seven had complete records and films available for review. Ninety-seven (49%) were treated with APBI (MammoSite) and 100(51%) were treated with external beam. Image findings for APBI versus external beam were: distortion 90(93%) versus 83(83%), seroma 67(69%) versus 7(7%), skin edema 52(54%) versus 47(47%), increased stroma 75(77%) versus 66(66%), calcifications 10(10%) versus 6(6%), and fat necrosis 12(12%) versus 6(6%). For APBI, skin and stromal edema was more commonly focal. At imaging, the seroma rate was statistically and significantly different between the two treatment modes (p < 0.0001). For patients treated with APBI, seroma formation was not related to balloon size and only weakly related to lumpectomy cavity size. The complication rate was significantly higher for those treated with APBI (36 versus 20%) and the types and treatment of complications differed. There were three recurrences among the APBI group and none among those treated with external beam radiation.     

Efficacy and safety of daily use of tadalafil in treatment of patients with premature ejaculation: A randomised placebo‐controlled clinical trial

The study aimed to evaluate the efficacy and safety of the once‐daily use of 5 mg tadalafil in the treatment of patients with premature ejaculation (PE). In a single‐blind placebo‐controlled clinical study, it was carried out on 100 patients with PE. All patients were randomised equally divided into two groups (50 patients each). Group 1 was given placebo in the form of oral multivitamin tablet once a day for 6 weeks. Group 2 was given 5 mg tadalafil once a day for 6 weeks. All patients were asked to complete Arabic Index of Premature Ejaculation (AIPE) before and after the treatment. This study showed that there were no statistically significant differences between patients in the placebo and tadalafil groups regarding the mean values of the seven questions and total scores of the AIPE questionnaire before treatment (p value >.05). The mean values of the seven questions and total scores of AIPE questionnaire in the tadalafil group were significantly higher than the placebo group after treatment (p value = .001). This study concluded that once‐daily use of 5 mg tadalafil for 6 weeks was effective and well tolerated in the treatment of patients with PE.     

Toxicity of docetaxel,carboplatin, and trastuzumab combination as adjuvant or neo‐adjuvant treatment for Her2 positive breast cancer patients and impact of colony‐stimulating factor prophylaxis

While the docetaxel, carboplatin, and trastuzumab (TCH) regimen is one of the standard treatments in Her2‐positive breast cancer, however, acute toxicities, especially those related to the high rate of neutropenia are consistently reported. Primary: To compare the toxicity of TCH in current clinical practice vs the toxicity observed in the pivotal study, comparing the toxicity in patients that received primary prophylaxis (PP) with colony‐stimulating factors vs those that did not receive PP. Secondary: To describe the demographic and clinical characteristics of the study sample, as well as the adverse effects and survival. The data regarding 95 patients were analyzed. Observed toxicity (hematological and extra‐hematological) was greater compared to the pivotal study, with the exception of neuropathy and neutropenia. Toxicities “PP” vs “no PP”: Extra‐hematological grade 3‐4 toxicities: Significant reduction was observed in the “PP” group vs the “no PP” group referred to fatigue, stomatitis, nausea, and vomiting. Hematological grade 3‐4 toxicities: Lesser neutropenia, leukopenia, and febrile neutropenia were observed in the “PP” group. Complications associated to treatment: No grade 3‐4 cardiac toxicity, leukemia or deaths were recorded. DFS and OS: After a mean follow‐up of 22.9 months, only one bone metastatic relapse was detected (DFS: 98.9%; OS: 100%). The combination TCH is very active and effective as adjuvant and neo‐adjuvant therapy in Her2‐positive breast cancer, and is currently regarded as standard treatment. However, global toxicity as well as hematological toxicity is elevated. The incorporation of PP to TCH significantly reduces hematological toxicity and some of the global toxicity, thus favoring treatment implementation and lessening the clinical complications. We therefore recommend generalization of PP with colony‐stimulating factors in patients receiving TCH.     

Surgery and pre-operative irradiation for locally advanced or recurrent rectal cancer in patients over 75 years of age

OBJECTIVE: Reports of multimodal treatment regimens especially focusing on locally advanced or recurrent rectal cancer in the elderly, aged>75 years, are unavailable. We have tried to identify and evaluate pre- and peri-operative risk factors for morbidity and mortality and outcome after irradiation/surgery regimens in such patients. PATIENTS AND METHODS: Prospective registration of 86 consecutive patients aged>75 years undergoing elective surgery after irradiation 46-50 Gy for either primary locally advanced rectal cancer (n=51) or recurrent rectal cancer (n=35) from January 1991 to August 2003, 51 men and 35 women, median age 78 years (range 75-85 years) in a national cancer hospital. RESULTS: Multivisceral resections were needed in 63% of patients and 70% R0 resections were obtained in locally advanced cases and 46% in recurrent ones. Both in-hospital- and 30-day-mortality was 3.5%. Sixty-two postoperative complications occurred in 38 patients, three of them fatal. Both operation times over 5 h and transfusion of more than 3 SAG were prognostic factors regarding infections. Estimated five-year survival in R0 patients was 46%. Estimated five-year survival for patients with nonmetastatic tumours with locally advanced primary cancer was 29% and for locally recurrent rectal cancer 32%. Old males had a higher mortality rate the first year after surgery than females with only 65% relative survival compared to a matched normal population. The estimated five-year local recurrence rates were 24% for R0 resections and 54% for R1 resections (P=0.434 ns) and 24% and 45% for locally advanced and recurrent rectal cancer (P=0.248 ns), respectively. CONCLUSION: Thorough pre-operative evaluation and preparation and judicious surgery are important for achieving potentially curative treatment with acceptable morbidity in locally advanced and recurrent rectal cancer in patients over 75 years of age. We suggest that these patients should be evaluated and considered for treatment by multidisciplinary teams as younger patients.     

Preliminary results and evaluation of MammoSite balloon brachytherapy for partial breast irradiation for pure ductal carcinoma in situ: a phase II clinical study

BACKGROUND: This report presents the preliminary results and evaluation of the MammoSite balloon catheter (MammoSite Radiation Therapy System; Cytyc Corporation, Marlboro, MA) as the sole method of delivering partial breast irradiation to the lumpectomy bed with breast-conserving surgery in patients with pure ductal carcinoma in situ (DCIS). METHODS: Twelve institutions are participating in this phase II clinical study. A total of 133 patients have been enrolled and 100 patients have successfully completed the prescribed radiation therapy. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose rate brachytherapy. Patients who met the following criteria were selected for enrollment into the study: age 45 years or older, unicentric pure DCIS, mammographic lesion of 3 cm or less, negative margins as defined by 1 mm or more, postoperative final gross pathologic size of tumor of 5 cm or less, clinically node negative, and a postlumpectomy mammogram showing the absence of any residual suspicious microcalcifications. The placement of the MammoSite catheter was performed either at the time of the lumpectomy or postlumpectomy. The minimum distance from the balloon surface to the surface of the skin is greater than 5 mm. Data collection points are at time of enrollment, time of implant, 3 months, 6 months, and then yearly at 1- to 5-year follow-up visits. Data collected are local control rates, cosmetic outcome using the Harvard Scale, toxicities, serious adverse events, disease-free survival, cause-specific survival, and contralateral breast failure. The Van Nuys Prognostic Index scores were calculated for each patient. Local recurrence is defined as either invasive or noninvasive recurrence within the target volume. Ipsilateral elsewhere recurrence is defined as either an invasive or noninvasive recurrence occurring outside of the target volume in the previously treated breast. This recurrence is classified as a new primary tumor. RESULTS: The mean follow-up period was 9.5 months (range, 1-24 mo). The MammoSite catheter was explanted for the following reasons: inadequate skin distance (5.1%; 6 of 117), poor cavity conformance (5.1%; 6 of 117), positive margins (2.6%; 3 of 117), final histology (.85%; 1 of 117), and physician decision (.85%; 1 of 117). Of the patients in whom the MammoSite was explanted because of skin spacing or cavity conformance, 50% were at sites of new users (institutions that have placed fewer than 10 Mammosite catheters). Cosmetic results were rated as excellent in 63%, good in 35%, and fair in 2% in the 86 patients with a follow-up visit. Two patients were diagnosed with an ipsilateral local recurrence, 1 outside of the target volume and 1 true recurrence/marginal miss. One patient was diagnosed at 8 months and the other was diagnosed at 11 months. Both of these ipsilateral failures were DCIS. The Van Nuys Prognostic Index of these 2 patients was 9 and 8, respectively. Data collected showed the mean age at placement was 60.8 y, mean tumor size was 10.6 mm, mean actual closest surgical margin was 6.8 mm (range, .1-40 mm), a re-excision rate of 35%, postlumpectomy placement was 71%, and the mean skin-to-balloon surface distance was 13 mm with 89% > or =7 mm. No serious adverse events were reported. The infection rate was 4.0%. CONCLUSIONS: Accelerated partial breast irradiation delivered with the MammoSite balloon was clinically successful in patients entered into a phase II clinical study with pure DCIS, with results comparable with other studies reported in the literature that have evaluated use of the MammoSite balloon brachytherapy for delivery of radiation therapy in early breast cancers. Inadequate skin distance and poor cavity conformance were the main factors limiting the use of the MammoSite device. Cosmetic results were good to excellent in 98%. There have been 2 ipsilateral breast recurrences.     

Liver regeneration following partial hepatectomy is improved by enhancing the HGF/Met axis and Akt and Erk pathways after low-power laser irradiation in rats

A simple, easy, and safe procedure aiming to improve liver regeneration could be of great clinical benefit in critical situations such as major hepatectomy, trauma, or hemorrhage. Low-power laser irradiation (LPLI) has come into a wide range of use in clinical practice by inducing regeneration in healthy and injured tissues. However, the effect of LPLI on the process of liver regeneration, especially those related to the molecular mechanisms, is not fully understood. Thus, the aim of the present study was to investigate the main molecular mechanisms involved in liver regeneration of partially hepatectomized rats exposed to LPLI. We used Wistar male rats, which had their remaining liver irradiated or not with LPLI (wavelength of 632.8 nm and fluence of 65 mW/cm²) for 15 min after a 70 % hepatectomy. We subsequently investigated hepatocyte growth factor (HGF), Met, Akt, and Erk 1/2 signaling pathways through protein expression and phosphorylation analyses along with cell proliferation (proliferating cell nuclear antigen (PCNA) and Ki-67) using immunoblotting and histological studies. Our results show that LPLI can improve liver regeneration as shown by increased HGF protein expression and the phosphorylation levels of Met, Akt, and Erk 1/2 accompanied by higher levels of the PCNA and Ki-67 protein in the remnant livers. In summary, our results suggest that LPLI may play a clinical role as a simple, fast, and easy-to-perform strategy in order to enhance the liver regenerative capacity of a small liver remnant after hepatectomy.     

Effects of taking tadalafil 5 mg once daily on erectile function and total testosterone levels in patients with metabolic syndrome

We aimed to evaluate the efficacy of tadalafil 5 mg once‐daily treatment on testosterone levels in patients with erectile dysfunction (ED) accompanied by the metabolic syndrome. A total of 40 men with metabolic syndrome were evaluated for ED in this study. All the patients received 5 mg tadalafil once a day for 3 months. Erectile function was assessed using the five‐item version of the International Index of Erectile Function (IIEF) questionnaire. Serum testosterone, follicle‐stimulating hormone and luteinising hormone levels were also evaluated, and blood samples were taken between 08.00 and 10.00 in the fasting state. All participants have three or more criteria of metabolic syndrome. At the end of 3 months, mean testosterone values and IIEF scores showed an improvement from baseline values (from 3.6 ± 0.5 to 5.2 ± 0.3, from 11.3 ± 1.9 to 19 ± 0.8 respectively). After the treatment, serum LH levels were decreased (from 5.6 ± 0.6 to 4.6 ± 0.5). There was significantly difference in terms of baseline testosterone and luteinising hormone values and IIEF scores (p < .05). Based on our findings, we recommend tadalafil 5 mg once daily in those men with erectile dysfunction especially low testosterone levels accompanied by metabolic syndrome.