Distal Tibia and Foot Involvement in a Patient With Waldenstrom's Macroglobulinemia.

Bone lesions are a rare presentation in Waldenstrom's macroglobulinemia patients. Although lytic bone lesions and generalized osteoporosis have been described variably in literature on Waldenstrom's macroglobulinemia patients, distal long bone and foot involvement has not been described to our knowledge. We report a patient with Waldenstrom's macroglobulinemia with IgM monoclonal spike, plasmacytic infiltration of bone marrow, and symptoms of foot pain, and found to have distal tibia and foot involvement. The symptoms of bone lesions in our patient were significantly improved with radiation treatment. The possibility of distal involvement of long bones in a clinically relevant presentation should be kept in mind in these patients.

Radiotherapy for benign calcaneodynia: long-term results of the Erlangen Dose Optimization (EDO) trial.

BACKGROUND AND PURPOSE: The goal of this work was to evaluate the long-term efficacy of two dose-fractionation schedules for radiotherapy of calcaneodynia. PATIENTS AND METHODS: Between February 2006 and February 2010, 457 evaluable patients were recruited for this prospective trial. All patients received orthovoltage radiotherapy. One course consisted of 6 fractions/3 weeks. In case of insufficient remission of pain after 6 weeks a second series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before, right after (early response), 6 weeks (delayed response), and approximately 2.5 years after radiotherapy (long-term response) with a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS). RESULTS: The median follow-up was 32 months (range 9-57 months). The overall early, delayed, and long-term response rates for all patients were 87, 88, and 95%. The mean VAS values before treatment, for early, delayed, and long-term response for the 0.5 and 1.0 Gy groups were 65.5 ± 22.1 and 64.0 ± 20.5 (p = 0.19), 34.8 ± 24.7 and 39.0 ± 26.3 (p = 0.12), 25.1 ± 26.8 and 28.9 ± 26.8 (p = 0.16), and 16.3 ± 24.3 and 14.1 ± 19.7 (p = 0.68). The mean CPS values before treatment, for early, delayed, and log-term response were 10.1 ± 2.7 and 10.0 ± 3.0 (p = 0.78), 5.6 ± 3.7 and 6.0 ± 3.9 (p = 0.34), 4.0 ± 4.1 and 4.3 ± 3.6 (p = 0.26), and 2.1 ± 3.3 and 2.3 ± 3.2 (p = 0.34), respectively. No significant differences in long-term response quality between the two arms were found (p = 0.50). CONCLUSION: Radiotherapy is a very effective treatment for the management of benign calcaneodynia. For radiation protection reasons, the dose for a RT series should not exceed 3.0 Gy.

[Malignant transformation of plantar ulcers in leprosy: experience of National Leprosy Center in Casablanca]. / Dégénérescence carcinomateuse des maux perforants plantaires d'origine lépreuse: expérience du Centre national de léprologie de Casablanca.

Malignant degeneration is a late complication of plantar ulcers in leprosy. The objective of this study is to describe and analyze the epidemiological, clinical, and therapeutic aspects of this complication in Morocco. A retrospective study was conducted from January 2000 to December 2009 at the National Center of Leprosy (CNL) in Casablanca. All our patients had a histological confirmation. Ten patients were included in this study. There were seven men and three women, with a mean age of 58.8 years. Six patients had a multibacillary form of leprosy and four had a paucibacillary form. The average duration of the plantar ulcers was 34.4 years. Clinical appearance at diagnosis was an ulcerative and vegetative tumor. Treatment was by radical amputation. Evolution was marked by metastatic spread in six patients. One patient died of disseminated disease. In Morocco, leprosy has been on the decline since 1990, but the occurrence of late complications in the leprosy patient as carcinoma of plantar ulcers persists. Prevention of these complications should be part of the national fight against leprosy.

Radiation therapy for early stages of morbus Ledderhose.

PURPOSE: To evaluate the efficacy of radiation therapy (RT) in the treatment of early stages of benign plantar fibromatosis (Morbus Ledderhose [ML]). PATIENTS AND METHODS: From 2003 to 2008, 24 patients (33 sites) with a mean age of 52 years received RT for symptomatic ML. Prior to RT, 19 patients complained of pain and 15 had walking difficulties. 21 patients (28 sites) were irradiated with orthovoltage X-rays and three (five sites) received electron-beam irradiation. The RT protocol consisted of five weekly fractions of 3.0 Gy (15 Gy), repeated after 6 weeks to a total dose of 30 Gy in 20 patients (28 sites). In four patients (five sites), two single fractions of 4.0 Gy were applied, repeated at intervals of 4 weeks to total doses of 24-32 Gy. Primary study endpoints were the prevention of disease progression and the avoidance of a surgical intervention. Secondary endpoints were pain relief, improvement of gait, and patients' subjective satisfaction measured with a linear analog scale (LAS). RESULTS: After a median follow-up of 22.5 months, none of the patients experienced a progression of number and size of the lesions or the clinical symptoms. In eleven sites (33.3%) complete remission of cords or nodules occurred, in 18 (54.5%) a reduced number or size was noted, and four sites (12.1%) were unchanged. Pain relief was achieved in 13/19 patients (68.4%), and an improvement of gait abnormalities was noted in 11/15 patients (73.3%). The patients' subjective satisfaction measured by means of the LAS revealed a median improvement of 3.5 points in 22/24 patients (91.6%). Skin or soft tissues toxicities RTOG grade > 2 were not noted. CONCLUSION: RT is effective for treatment of the early stages of ML and may obviate the need for a surgical intervention. Long-term follow-up studies including a larger number of patients are required to define the role of RT in the management of this disorder.

Eccrine syringofibroadenoma radiation treatment of an unusual presentation.

Benign skin diseases have seldom been treated with radiotherapy, unless resistant to other treatments. Eccrine syringofibroadenoma (ESFA) is a rare benign eccrine tumor. ESFA very rarely presents bilateral lesions, and seldom a nonsurgical treatment has been proposed. An exceptional case of bilateral ESFA of the foot is presented; radiotherapy was effective in treating both lesions with good cosmetic results.

[Pagetoid reticulosis in a patient with mycosis fungoides. Successful therapy with localized electron beam irradiation]. / Pagetoide Retikulose bei einem Patienten mit Mycosis fungoides. Erfolgreiche Therapie mit lokalisierter Elektronenbestrahlung.

Pagetoid reticulosis is a mycosis fungoides subtype. It is characterized by a prominent epidermotropism, localized lesions, slow progression and benign prognosis. We report on a 67-year-old patient with a history of classic mycosis fungoides, who developed pagetoid reticulosis on the right heel. Local electron beam therapy induced a complete remission, with no recurrence over three months of follow-up.

Boron neutron capture therapy for clear cell sarcoma.

Clear cell sarcoma of tendons and aponeuroses (CCS) is a rare, malignant tumor arising in lower extremities with no effective treatment other than wide surgical resection. Here described is a case of primary CCS in the peroneal tendon of the right foot of a 54-year-old woman enrolled to undergo BNCT. The tumor mass post-BNCT disappeared totally without damage to other normal tissue, demonstrating, for the first time, the potential efficacy of BNCT in complete local control of CCS.

Radiotherapy for calcaneodynia, achillodynia, painful gonarthrosis, bursitis trochanterica, and painful shoulder syndrome - Early and late results of a prospective clinical quality assessment.

BACKGROUND: The aim of this prospective clinical quality assessment was to evaluate the short-term and long-term efficacy of low dose radiotherapy (RT) for calcaneodynia, achillodynia, painful gonarthrosis, painful bursitis trochanterica, and painful shoulder syndrome. METHODS: Between October 2011 and October 2013, patients with calcaneodynia, achillodynia, painful gonarthrosis, painful bursitis trochanterica, and painful shoulder syndrome were recruited for this prospective clinical quality assessment. Single doses of 0.5-1.0 Gy and a total dose of 6.0 Gy per series were used. Pain was measured before and directly after RT (early response) with a visual analogue scale (VAS). Additionally, pain relief was measured with the four-scale pain score according to "von Pannewitz" (VPS) immediately at the end of RT and during follow-up. Within this context we defined a good response as complete pain relief and markedly improved. The assessment of the long-term efficacy was carried out by a telephone survey. RESULTS: 703 evaluable patients (461 female, 242 male) with a mean age of 63.2 years (28-96) were recruited for this prospective clinical quality assessment. In 254 patients RT was performed with the linear accelerator, 449 patients received orthovoltage radiotherapy. After a median follow-up of 33 months (3-60) 437 patients could be reached for evaluation of follow up results. The mean VAS value before treatment was 6.63 (1.9-10) and immediately on completion of RT 4.51 (0-10) (p < 0,001). Concerning the VPS immediately on completion of RT, a good response could be achieved in 264/703 patients (37.6%), and with the follow up in 255/437 patients (58.4%) (p < 0.001). Only in patients with gonarthrosis we could not observe a significantly improved long-term success in comparison to the results immediately after RT (30.2% versus 29.9%). CONCLUSION: Low dose RT is a very effective treatment for the management of calcaneodynia, achillodynia, painful gonarthrosis, painful bursitis trochanterica, and painful shoulder syndrome. Due to the delayed onset of analgesic effects low dose RT results in a significantly improved long-term efficacy in comparison to the results immediately after RT particularly in patients with calcaneodynia, achillodynia, bursitis trochanterica, and shoulder syndrome.

Inhibitory effects of prior low-dose x-irradiation on ischemia-reperfusion injury in mouse paw.

We have reported that low-dose, unlike high-dose, irradiation enhanced antioxidation function and reduced oxidative damage. On the other hand, ischemia-reperfusion injury is induced by reactive oxygen species. In this study, we examined the inhibitory effects of prior low-dose X-irradiation on ischemia-reperfusion injury in mouse paw. BALB/c mice were irradiated by sham or 0.5 Gy of X-ray. At 4 hrs after irradiation, the left hind leg was bound 10 times with a rubber ring for 0.5, 1, or 2 hrs and the paw thickness was measured. Results show that the paw swelling thickness by ischemia for 0.5 hr was lower than that for 2 hrs. At 1 hr after reperfusion from ischemia for 1 hr, superoxide dismutase activity in serum was increased in those mice which received 0.5 Gy irradiation and in the case of the ischemia for 0.5 or 1 hr, the paw swelling thicknesses were inhibited by 0.5 Gy irradiation. In addition, interstitial edema in those mice which received 0.5 Gy irradiation was less than that in the mice which underwent by sham irradiation. These findings suggest that the ischemia-reperfusion injury is inhibited by the enhancement of antioxidation function by 0.5 Gy irradiation.

Anti-inflammatory effects of low-level laser therapy (LLLT) with two different red wavelengths (660 nm and 684 nm) in carrageenan-induced rat paw edema.

It has been suggested that low-level laser therapy (LLLT) can modulate inflammatory processes. The aim of this experiment was to investigate what effects red laser irradiation with two different wavelengths (660 nm and 684 nm) on carrageenan-induced rat paw edema and histology. Thirty two male Wistar rats were randomly divided into four groups. One group received a sterile saline injection, while inflammation was induced by a sub-plantar injection of carrageenan (1 mg/paw) in the three other groups. After 1 h, LLLT was administered to the paw in two of the carrageenan-injected groups. Continuous wave 660 nm and 684 nm red lasers respectively with mean optical outputs of 30 mW and doses of 7.5 J/cm(2) were used. The 660 nm and 684 nm laser groups developed significantly (p<0.01) less edema (0.58 ml [SE+/-0.17] ml and 0.76 ml [SE+/-0.10] respectively) than the control group (1.67 ml [SE+/-0.19]) at 4h after injections. Similarly, both laser groups showed a significantly lower number of inflammatory cells in the muscular and conjunctive sub-plantar tissues than the control group. We conclude that both 660 nm and 684 nm red wavelengths of LLLT are effective in reducing edema formation and inflammatory cell migration when a dose of 7.5 J/cm(2) is used.

Neoadjuvant radiotherapy for myxoid liposarcomas: Oncologic outcomes and histopathologic correlations.

OBJECTIVE: The aim of this study was to evaluate the histopathological features of primary extremity myxoid liposarcoma before and after neoadjuvant radiation therapy, and to evaluate the oncological outcomes of the patients. METHODS: The study included 23 patients (16 men and 7 women with a mean age of 43 (24-69) years) with primary myxoid liposarcoma of the extremities, who were treated between January 1998 and December 2015. Inclusion criteria were histopathological confirmation of the diagnosis with both the initial biopsy and the resection specimen, and having undergone neoadjuvant radiotherapy. Demographic, clinical and histopathological data were evaluated. RESULTS: Over a mean follow-up time of 55.2 (8-139) months, 5 patients (21.7%) died secondary to disease progression, leaving 18 patients (78.3%) still alive at the time of last follow-up. Only one patient (4%) experienced local recurrence and six (26%) patients developed distant metastases. Disease-free survival at 5 and 10 years were 66%; whereas, overall patient survival at 5 and 10 years were 78.1% and 71.0%, respectively. Tumor size (>15 cm) and presence of metastasis were significantly associated with increased overall mortality. On histopathology, necrosis was present in 12/23 resection specimens. Hyalinization/fibrosis and residual viable tumor was present in all specimens. Adipocytic maturation/cytodifferentiation was seen in 8/23 patients. CONCLUSION: Neoadjuvant radiotherapy was effective for myxoid liposarcomas histopathologically, although these histopathological features did not affect the patients' oncological outcomes. Favorable oncological outcomes were obtained with neoadjuvant radiotherapy, surgical resection and chemotherapy. LEVEL OF EVIDENCE: Level IV, therapeutic study.

99mTc-DPD SPECT/CT for localisation of inflammatory and chronic osteoarthritis of the foot and ankle. Comparison with planar imaging and SPECT as a clinical adjunct in radiosynovectomy.

AIM: The precise localisation of osteoarthritic and inflammatory changes is crucial for selective treatment planning of radiosynovectomy (RSV). The present study evaluated the diagnostic accuracy of planar bone imaging and SPECT for the detection of pathological bone metabolism and inflammation in joints of the foot and ankle, compared with SPECT/CT. PATIENTS, METHODS: 39 patients (mean age 65.6 ± 11.1 years) with suspected inflammatory osteoarthritis underwent SPECT/CT of the feet. After injection of approximately 500 MBq 99mTc DPD, all patients had three-phase planar bone imaging and late-phase hybrid SPECT/CT. late-phase SPECT, and CT of the foot. Increased bone metabolism and blood-pool was assigned to the respective joint of the fore-, mid-, and hindfoot, using SPECT/CT as the reference standard. RESULTS: Overall, SPECT had a higher sensitivity than planar imaging (0.80 vs 0.68, n.s.). The advantage of SPECT was most obvious in the anatomically complex midfoot area (0.63 vs 0.26, p < 0.05) and less obvious in the forefoot (0.85 vs 0.79, n.s.) and hindfoot (0.89 vs 0.89, n.s.). The overall concordance (Cohen`s Kappa) between SPECT/CT and planar (late-phase) imaging and SPECT was high for the forefoot and the hindfoot (planar: 0.78/0.81; SPECT 0.86/0.88) and comparatively low for the midfoot (planar: 0.27; SPECT 0.61). CONCLUSION: SPECT was significantly superior to planar bone imaging for the detection of joint lesions in the midfoot. The differences between SPECT and planar imaging in the fore- and hindfoot were not significant, most likely due to the inherently less complex anatomy. Compared with SPECT alone, a benefit from the use of SPECT/CT can be observed in the midfoot region where it facilitates the identification of the correct joint for RSV.

Combined Limb-Sparing Surgery and Radiation Therapy to Treat Sarcomas of the Hands and Feet: Long-Term Cancer Outcomes and Morbidity.

PURPOSE: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with limb-sparing surgery and radiation therapy (RT) for soft tissue sarcomas (STS) of the hands and feet. METHODS AND MATERIALS: We reviewed the medical records of 85 consecutive patients treated for STS of the hands (n=38, 45%) and feet (n=47, 55%) between 1966 and 2012. The median age was 41 years (range, 10-82 years of age). Sixty-seven patients (79%) received postoperative RT after resection of their tumor (median dose, 60 Gy; range, 45-70 Gy). The remaining 18 patients (21%) were treated with preoperative RT followed by tumor resection (median dose, 50 Gy; range, 50-64 Gy). RESULTS: Median follow-up was 140 months (range, 24-442 months). Five-year local control, overall survival, and disease-specific survival rates were 86%, 89%, and 89%, respectively. Positive or uncertain surgical margin status was the only factor adversely associated with local recurrence (19% vs 6% for negative margins, P=.046) but this lost significance on multivariate analysis when adjusting for RT dose ≥64 Gy. Of the 12 patients who had local relapses, 6 (50%) were salvaged, and only 2 of those required salvage amputation. Five patients had grade ≥3 late RT sequelae, with 2 patients (2%) having moderate limitations of limb function and 3 patients (4%) having severe limitations requiring procedures for skin ulceration. CONCLUSIONS: Limb-sparing surgery combined with RT provides excellent local control outcomes for sarcomas arising in the hands or feet. In patients who have local recurrence, salvage without amputation is possible. The excellent cancer control outcomes observed, considering the minimal impact on limb function, support use of combined modality, limb-sparing local therapy for STS arising in the hands or feet.

Individualizing management of aggressive fibromatoses.

PURPOSE: To examine prognostic indicators in aggressive fibromatoses that may be used to optimize case-specific management strategy. METHODS AND MATERIALS: One hundred and seven fibromatoses presenting between 1971 and 1992 were analyzed. The following treatment modalities were utilized: (a) surgery alone for 51 tumors; (b) radiation alone for 15 tumors; and (c) radiation and surgery (combined modality) for 41 tumors. Outcome analysis was based on 5-year actuarial local control rates. RESULTS: Control rates among surgery, radiation therapy, and combined modality groups were 69%, 93%, and 72%. Multivariate analysis identified age < 18 years, recurrent disease, positive surgical margins, and treatment with surgery alone as predictors for failure. Patients treated with surgery alone had control rates of 50% (3 of 6) for gross residual, 56% for microscopically positive margins, and 77% for negative margins. Radiation and surgery resulted in rates of 59% for gross residual, 78% for microscopically positive margins, and 100% (6 of 6) for negative margins. For recurrent vs. primary tumors, control was achieved in 48% vs. 77%, 90% vs. 100% (5 of 5), and 67% vs. 79% in the Surgery, Radiation, and Combined modality Groups, respectively. Patients presenting with multiple disease sites tended to have aggressive disease. A radiation dose-control relation to > 60 Gy was seen in patients with unresected or gross residual disease. Of the patients, 23 with disease involving the plantar region had a control rate of 62%, with significantly worse outcomes in children. CONCLUSIONS: These results are consistent with those found in the relevant literature. They support primary resection with negative margins when feasible. Radiation is a highly effective alternative in situations where surgery would result in major functional or cosmetic defects. When negative surgical margins are not achieved in recurrent tumors, radiation is recommended. Perioperative radiation should be considered in other high-risk groups (recurrent disease, positive margins, and plantar tumors in young patients). Doses of 60-65 Gy for gross disease and 50-60 Gy for microscopic residual are recommended. Observation may be considered for primary tumors with disease remaining in situ when they are located such that progression would not cause significant morbidity. Although plantar lesions in children may represent a group at high risk for recurrence or aggressive behavior, the greater potential for radiation-induced morbidity in this group must also temper its use. Given the inconsistent nature and treatment response of this tumor, it is fundamental that treatment recommendations should be made based on the risk:benefit analysis for the individual patient, dependent on tumor characteristics and location, as well as patient characteristics and preferences.

Limb salvage therapy for soft tissue sarcomas of the foot.

From 1974 to 1988, 20 patients with soft tissue sarcomas of the foot underwent attempted limb preservation at UCLA. Eighteen patients had localized tumor and two had metastases. Sixteen patients had previously untreated tumors and four patients had experienced 2-4 local recurrences before definitive management. Eleven patients had grade 3 sarcomas and nine had grade 2 sarcomas. Fourteen patients had an excisional biopsy and six had an incisional biopsy. At the time of definitive local treatment, nine patients had palpable tumor ranging from 2-10 cm (median 5 cm). Sixteen patients received sequential preoperative chemotherapy and irradiation followed by attempted conservative resection. Four patients underwent immediate conservative resection followed by postoperative irradiation. Preoperative chemotherapy was administered over 3 days intraarterially, intravenously or by a combination of routes. Fifteen patients received 60-90 mg doxorubicin and one received 120 mg doxorubicin plus 220 mg cisplatinum. Preoperative irradiation was delivered in 350 cGy fractions to total doses of 3500 cGy (one patient), 2800 cGy (8) or 1750 cGy (7). Postoperative irradiation doses were 4140-6480 delivered in 180-200 cGy fractions. Fifteen of 16 preoperatively treated patients had limb salvage surgery. Four of these 15 had positive histopathologic margins and none received postoperative irradiation. One patient required a primary amputation due to gross involvement of the os calcis. Three of four patients undergoing immediate conservative excision had positive margins and one had gross residual disease. Five patients received chemotherapy following local treatment: 3 adjuvantly and 2 for metastatic disease. Follow-up for salvage patients ranged from 6 to 99 months (median 36). Local control was achieved in 17 of 19 (90%). Two patients recurred in-field at 24 and 30 months. Fourteen of 15 preoperatively treated and salvaged patients maintained local control. Three of four managed with excision and postoperative irradiation were controlled. The actuarial local control at 3 years was 83%. One patient recurred in the inguinal lymph nodes and three patients died of metastatic disease. The actuarial survival and relapse-free survival at 3 years were 83% and 63%. Eleven patients developed acute complications and four had late complications. Of 14 patients surviving with local control, function was good or excellent in 86%. No patient has required an amputation for complications or a dysfunctional foot. Limb salvage therapy for a selected patient with a soft tissue sarcoma of the foot can reasonably be expected to result in a high probability of local control and useful function without compromising survival.

Are hypoxic cells critical for the outcome of fractionated radiotherapy in a slow-growing mouse tumor?

PURPOSE: To investigate the significance of hypoxic cells, reoxygenation and repopulation for the outcome of fractionated radiotherapy of a slow-growing subline of a murine fibrosarcoma and to compare the results with those previously obtained from the original fast-growing tumor. MATERIALS AND METHODS: A slow-growing subline, 457-O, was obtained among the tumors that recurred after a single irradiation to the third generation isotransplants of a mouse fibrosarcoma, FSa-II. The single cell suspensions were transplanted into the mouse foot and when the tumors reached an average diameter of 4 mm, they were subjected to one to 20 equal daily y-ray doses given in air (A) or under hypoxic conditions (H). The TCD50 (50% tumor control radiation dose) was calculated according to the tumor control frequency within 180 days. The linear-quadratic plus time model was fitted to these data by logistic regression analysis. RESULTS: The volume doubling time of the 457-O tumors was approximately 2.2 times slower than that of the original FSa-II tumors. The TCD50(H) (single dose) was 52.3 Gy and increased with an increasing number of fractions to a TCD50(H) (20 doses) of 90.8 Gy. This increase of 38.5 Gy was much smaller than that of 149 Gy for the original FSa-II. The TCD50(A) (single dose) and TCD50(A) (20 doses) were 41.3 and 50.6 Gy, respectively. This small difference of 9.3 Gy contrasted with a significant increase of 52.9 Gy for the FSa-II. DISCUSSION: These results suggested no repopulation of 457-O tumor clonogens during the course of up to 20 daily doses, while the original FSa-II tumor cells repopulated substantially. Hypoxic clonogens in the slow-growing tumor reoxygenated but some fractions remained critical. CONCLUSION: The present data together with those obtained from the fast-growing FSa-II suggested that hypoxic clonogens were critical for the outcome of fractionated radiotherapy. Repopulation was insignificant in this slow-growing tumor during five to 20 daily doses.