The genotoxic effects in lymphocyte cultures of children treated with radiosynovectomy by using yttrium-90 citrate colloid

The aim of this study was to investigate the genotoxic effect on the peripheral blood lymphocytes potentially induced by yttrium-90 citrate colloid (Y-90) in children who were undergoing radiosynovectomy for hemophilic synovitis, using chromosomal aberration analysis (CA) and the micronuclei (MN) assay for detecting chromosomal aberrations, as well as the sister chromatid exchanges (SCE) technique for assessed DNA damage. MATERIALS AND METHODS: Cytogenetic analyses were undertaken in 18 boys (mean age, 14.5 +/- 2.1 years) with hemophilic synovitis who underwent radiosynovectomy with Y-90. CA, MN, and SCE were evaluated just prior to, then at 2 and 90 days following radiosynovectomy from the peripheral lymphocytes of the children. An activity of 185 MBq of Y-90 was injected into the 18 knee joints under aseptic conditions. To check the possibility of leakage from the joint and its migration within the body, the patients underwent scanning under a dual-headed gamma camera at the hours 2 and 48 following the procedure. RESULTS: The procedure was well tolerated in all the children, and there was no extra-articular activity owing to extra-articular leakage of radioactive material in whole-body imaging. The mean frequency of CA in lymphocytes determined prior to the onset of therapy (0.31 +/- 0.48/900 cells) was not significantly increased, in comparison to the control values obtained 2 (0.30 +/- 0.48/900 cells) and 90 days (0.15 +/- 0.37/900 cells) after radiosynovectomy (p = 1.0 and 0.625, respectively). We observed that MN frequency was mildly increased in lymphocytes 2 days after therapy (8.30 +/- 1.89 MN/1000 binucleated cells vs. 9.23 +/- 1.79 MN/1000 binucleated cells; p = 0.013). But there was no significant difference between the baseline and the day 90 control levels of MN (p = 0.196). In the analysis of SCE frequency, there were no significant differences between the baseline (8.11 +/- 0.77) and the control analysis performed 2 and 90 days following radiosynovectomy (8.18 +/- 0.77 and 8.07 +/- 0.74; p = 0.710 and 0.662, respectively). CONCLUSIONS: The results of this study indicated that high radiation doses are not obtained by peripheral lymphocytes of children who undergo Y-90 radiosynovectomy and, therefore, they contradict a high cancer risk.     

Radiosynoviorthesis for treatment of hemophilic hemarthrosis--Slovenian experience

Radiosynoviorthesis is a well-accepted method for the treatment of recurrent hemarthrosis in hemophilic patients. OBJECTIVES: The aims of our study were to evaluate the effectiveness of radiosynoviorthesis in patients suffering from hemophilic hemarthrosis, to determine the effect of treatment on antihemophilic factor consumption, and to assess the patient's satisfaction with radiosynoviorthesis. METHODS: Between 2001 and 2003, 26 radiosynoviortheses were done in 21 hemophilic patients; in 4 patients the treatment was repeated, and in 1 patient two joints were treated. 90Y colloid was used for the knee joint, and 186Re colloid was used for ankle, shoulder, and elbow radiosynoviorthesis. RESULTS: The bleeding frequency decreased by at least 50% in 53% of patients in the year after radiosynoviorthesis, as compared to the year prior to the therapy. Considering only those patients who had at least 12 bleedings into the treated joints in the year preceding the therapy, the bleeding frequency decreased by at least 50% in 62% of these patients. In this group, the consumption of the antihemophilic factor was notably reduced (on average, by 25,800 I.U./year). All patients reported that the treated joint was much better or better than before the radiosynoviorthesis. CONCLUSION: Radiosynoviorthesis is an effective method for the treatment of hemophilic hemarthrosis, particularly in patients with frequent intra-articular bleedings. The antihemophilic factor consumption was markedly reduced only in patients with frequent joint bleeding. Radiosynoviorthesis is well accepted by patients suffering from hemophilic hemarthrosis.     

Effects of radiosynovectomy with p-32 colloid therapy in hemophilia and rheumatoid arthritis

AIM: The aim of this study was to assess the effects of treatment with our locally produced P-32 colloidal suspension on knee synovitic inflammations of hemophilic and rheumatoid arthritis (RA) patients, as well as to compare results with chemical synovectomy or corticoid intra-articular injections and evaluate the cost-benefit ratio. MATERIALS AND METHODS: Thirty-six hemophilic male patients, 4-28 years of age and sent by the Hemophilic Foundation (Buenos Aires, Argentina), were enrolled for knee radiosynovectomy (RS) with P-32 colloid (26 patients), or the antibiotic rifampicin with the cooperation of orthopaedists (10 patients). Parents' informed consent was obtained. The following procedures were performed: routine blood tests, X-ray, ultrasound, a 3-phase bone scan, plus monthly methylene diphosphonate (MDP) controls. Patients were included in this study only if several knee episodes had occurred. Exclusion criteria included bone destruction and big Baker's cyst. Twelve RA patients were included, with similar selection criteria: 6 RA patients received P-32 therapy, and the other 6 patients intra-articular corticoids. Clinical, blind evaluation (state of joint involvement, pain, motility, requirements of antihemophilic factors, corticoids, or analgesics) was registered in follow-up charts. If required, joint aspiration was carried out. Intra-articular instillation of saline plus flushing was done before the needle was withdrawn. P- 32 Bremsstrahlung emission was used in the gamma camera for early and late imaging to confirm the absence of leakage. For intra-articular chemical injections therapy, 4 MBq of Tc-99m MAA (macroaggregates) was used. Immobilization and relative rest for 72 hours followed the procedures. RESULTS: There were neither local or systemic effects, nor leakage during P-32 treatment. Intra-articular rifampicin and corticoids procedures required frequent injections. Comparison of regions of interest (ROIs) in treated knees during soft-tissue scintigraphies in pre- and post-third MDP control showed knee improvement. The follow-up evaluation demonstrated an increase in joint motion, diminished volume, and less requirement and frequency of the use of antihemophilic factors (AHF) in 80% of the radiosynovectomies (21 of 26), thus lowering health costs. Five female RA patients (5 of 6) had decreased joint swelling and pains, resulting in increased joint motion. CONCLUSIONS: Radiosynovectomy in RA showed a 3-month pain palliative effect. One intra-articular knee radiosynoviorthesis in haemophilic patients provides a more than 3- month relief of symptoms after treatment with locally produced P-32 (11 patients). This turned out to be a safe, economic alternative procedure in emerging nations where the availability of AHF is difficult and expensive.     

Radiosynoviorthesis in osteoarthritis and other disorders with concomitant synovitis in comparison to rheumatoid arthritis

AIM: The aim of this study was to evaluate the effectiveness of radiosynoviorthesis (RSO) in osteoarthritis and other disorders with concomitant synovitis versus rheumatoid arthritis by means of a standardized questionnaire. METHODS: Eight-hundred and three RSO treatments were monitored in 691 patients by seven centers in three countries, using standardized questionnaires. Patients were assigned to three groups according to their age (20-40, 41-60, and 61-80 years). Additionally, the data was analyzed separately for patients with rheumatoid arthritis (group A) and those with osteoarthritis, psoriasis arthritis, pigmental villonodular synovitis, or persistent effusions after joint replacement (group B). RESULTS: Quality of life improved in 78% of group A and 59% of group B (p < 0.01). Ameliorations of joint pain, swelling/effusion, or flexibility were found in 80% of group A and 56% of group B (p < 0.01). The response rate was similar for small- and large-sized joints in group A, but was significantly higher for large-sized joints in group B (p < 0.01). The positive effects on joint pain, swelling/effusion, or flexibility lasted longer in group A (p < 0.01). Repeated RSOs were as effective as initial RSOs. The clinical outcome was not influenced by age, gender, or transient immobilization for 48 hours after RSO. CONCLUSION: Although slightly more efficient in rheumatoid arthritis, RSO represents an effective treatment option also in osteoarthritis and other disorders with concomitant synovitis.     

关节镜辅助下股骨逆行髓内钉取出术五例报告

目的探讨关节镜辅助下股骨逆行髓内钉取出术的应用。方法2006年6月至2009年3月,我院关节镜辅助下取出股骨逆行髓内钉5例。结果本组5例均获得随访,所有患者均在术后第3天即下床行走,术后12天拆除切口缝线,未出现关节僵硬或关节感染,出院时膝关节活动度与入院前一致。结论关节镜辅助下股骨逆行髓内钉取出术切口小、出血少,关节腔基本不暴露,感染机会少,术后膝关节功能恢复快,可避免长时间使用拉钩对髌腱、髌软骨及髌下脂肪垫等关节内组织和结构的损伤;能行关节内探查,同时处理关节内病变。     

血友病性髋关节炎患者的全髋关节置换四例报告

目的 探讨全髋关节置换术治疗血友病性髋关节炎的短、中期临床疗效。方法 回顾分析 2004 年５月至 2010 年９月,采用人工髋关节置换术治疗晚期血友病性髋关节炎患者４例。患者均为男性,年龄 34～56 岁,平均年龄 45 岁。按 Arnold and Hilgartner 分级：IV 级２例,Ｖ级２例。围手术期给予患者凝血因子替代治疗的基础上,对４例患者行人工髋关节置换术,手术采用髋关节前外侧标准入路。术中、术后监测相应凝血因子活性水平控制术后出血,密切关注并发症的发生。术后根据关节功能改善情况、Harris 评分、假体生存情况、术后并发症等评估手术治疗效果。结果 本组４例患者均获随访,随访时间９个月至７年,平均 40 个月。４例患者术后髋关节疼痛均明显减轻,３例患者术后髋关节疼痛消失,１例患者术后偶诉疼痛,但不影响生活。术后 Harris 评分：85～90 分 （优２例,良２例）,平均 87.7 分。术中出血量及引流量：平均每侧髋关节为 1210 ml。本组第１例患者术后 84 个月右侧髋臼处出现松动迹象,现拟行翻修手术治疗;余患者均未出现假体周围骨溶解及松动的征象,假体位置和力线水平均满意。１例术后出现关节内出血并切口渗血,无 DVT 和 PE 形成,无大出血及伤口感染。手术切口均Ｉ期愈合。结论 人工髋关节置换术可明显缓解晚期血友病性关节炎患者的关节疼痛,明显改善病变髋关节功能,短、中期疗效较好。合理的围手术期凝血因子替代治疗非常重要,血友病性髋关节炎行人工关节置换术难度较大,对手术技术要求很高,需要专业的手术团队并在内科医师配合下施行。     

色素性绒毛结节性滑膜炎——附16例报告

目的探讨色素沉着性绒毛结节性滑膜炎对关节周围组织侵袭的机理、临床诊断和外科治疗。方法16例四肢骨关节内的色素绒毛结节性滑膜炎经手术、病理确诊。膝关节7例、髋关节3例、踝关节2例、肩、肘关节各2例。X线片显示膝关节为侵入性骨质破坏，髋、踝关节多为关节面的腐蚀性破坏。结果16例均行关节内病变滑膜组织切除术，并对受累的骨质进行刮除。随防6个月～18年，无局部复发。结论色素绒毛结节性滑膜炎侵及骨质较少见，临床及X线表现更无典型特征，术前确诊率不高。治疗以滑膜彻底切除为主，对骨质破坏严重的病例，可行关节成形术或关节置换术。     

Positive Contrast Arthrography of the Normal Mid-Tarsal Joints

The radiological anatomy of the mid-tarsal joints has been discussed. This includes the calcaneo-cuboid joint and the anterior talocalcaneo-navicular joint. The talo-calcaneo-navicular joint has a capacity of 4–5 ml., while the calcaneo-cuboid joint has a capacity of 1–5 ml. The arthrography pattern of these joints was demonstrated for the first time at post-mortem. It is the key to successful paracentesis and intra-articular iniections of steroids.     

Osteosarcoma near joints: assessment and implications

BACKGROUND: The choice of performing surgery when tumors encroach onto joints remains a challenging and controversial issue. Pre-operative assessment by magnetic resonance imaging (MRI) is of critical importance in dictating surgical management and subsequent functional outcome. METHODS: We examined archival samples from 27 patients with osteosarcoma, adjacent to synovial joints for the incidence and mechanism of osteosarcoma extension into the joint space. Histopathologic findings were correlated with pre-operative MRI findings and choice of operation. RESULTS: There was no evidence of penetration across the entire thickness of articular cartilage into the joint cavity in all of the 27 cases. When pre-operative MRI confidently excluded joint involvement by tumor, enabling an intra-articular surgical approach, histopathologic correlation confirmed the absence of joint involvement in all cases. The low incidence of joint involvement was despite the presence of extensive bone and soft tissue involvement in most cases, a tendency for peripheral extension of tumor around the articular margin of the bone, and evidence of joint effusions pre-operatively in more than one-third of cases. CONCLUSIONS: Joint involvement by osteosarcoma is uncommon, with articular cartilage being a relative barrier to tumor invasion. If pre-operative MRI does not show definite evidence of intra-articular tumor involvement, it is likely to be safe to proceed with intra-articular resection.     

Oligometastatic Rectal Adenocarcinoma Treated With Short-Course Radiation Therapy and Chemotherapy With Nonoperative Intent of the Primary for Locoregional Complete Responders

PurposeNonoperative management with short-course radiation therapy (SCRT) as a component of definitive therapy for oligometastatic rectal cancer has not been previously reported. This single-institution retrospective analysis evaluates treatment with SCRT in combination with chemotherapy (SCRT-CTX) with nonoperative intent for patients with a locoregional clinical complete response (cCR).Methods and MaterialsThirty-six patients with newly diagnosed oligometastatic rectal cancer were treated with SCRT-CTX between January 1, 2018, and May 31, 2020. Digital rectal examination, endoscopy, and imaging (computed tomography or magnetic resonance imaging) were used to determine cCR. Medically operable patients without cCR underwent surgical resection of the primary rectal tumor. Patients with cCR who experienced a local failure received salvage surgery. Rates of hospitalization related to primary tumor disease and pelvic symptoms were reviewed. Overall survival (OS) and progression free survival were evaluated.ResultsSeventeen percent (6/36) of patients achieved cCR after SCRT-CTX. Eleven percent (4) of patients experienced a local failure. OS for all patients was 83% (71%-96%) at 12 months and 57% (41%-80%) at 24 months. Progression free survival for all patients was 56% (41%-74%) at 12 months and 10% (3.1%-35%) at 24 months. On multivariate analysis, having received more than 4 months of chemotherapy (hazard ratio = 0.21; 95% confidence interval, 0.06-0.71; P = .01) and definitive treatment of metastatic site (hazard ratio = 0.17; 95% confidence interval, 0.05-0.66; P = .01) predicted for improved OS. The number of patients requiring hospitalization due to obstruction (8/36, 22%), rectal bleeding (5/36, 14%), or need for permanent ostomy placement (5/36, 14%) was low, and there was a decrease in endorsement of obstructive symptoms and rectal bleeding after completion of SCRT-CTX.ConclusionsSCRT-CTX with nonoperative intent for patients with a locoregional cCR may be a reasonable treatment option for patients with newly diagnosed oligometastatic rectal adenocarcinoma and demonstrates excellent control of pelvic disease and symptoms. Increased duration of chemotherapy within the treatment paradigm may improve oncologic outcomes.     

盐酸氨基葡萄糖协同关节腔内注射玻璃酸钠治疗膝关节骨关节炎疗效观察

目的观察比较口服盐酸氨基葡萄糖胶囊、关节腔内注射玻璃酸钠以及二者联合使用对膝关节骨关节炎的疗效。方法将150例膝关节骨关节炎患者随机分为3组（口服盐酸氨基葡萄糖胶囊、关节腔内注射玻璃酸钠以及联合用药组）,每组各50例,分别给予单独口服盐酸氨基葡萄糖胶囊（0．75g,2次/d）、单独关节腔注射玻璃酸钠（2ml,1次倜）及二者联合使用。关节腔注射玻璃酸钠疗程为5周,口服盐酸氨基葡萄糖胶囊疗程为8周,疗效观察时间为12周。采用Lequesne指数作为疗效评分标准,观察治疗前后膝关节症状变化包括休息痛、运动痛、压痛、肿胀、晨僵和行为能力的改善程度。结果3组患者第4、8、12周时分别与同组第1周时疗效比较均有改善（P〈0．05）,第4周时注射组和联合组疗效均优于口服组（P〈0．05）,第8周时3组疗效无显著差异,第12周时联合组疗效优于口服组和注射组（P〈0．05）。结论口服盐酸氨基葡萄糖协同关节腔内注射玻璃酸钠治疗膝关节骨关节炎效果更快,疗效更佳。     

The treatment choices and outcome of hepatocellular carcinoma in hemophilic patients with human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfection due to contaminated blood products in Japan

BackgroundHuman immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection through unheated blood product for hemophilia caused in early 1980s has been significantly serious problem in Japan. After the development of HIV treatment in 1990s, HCV-related hepatocellular carcinoma (HCC) has been one of the most significant problem in these population. Treatment choices for HCC might be limited in hemophilia patients because of their bleeding tendency. The aim of this study was to elucidate the treatment choices and outcome of HCC in hemophilic patients coinfected with HIV/HCV due to contaminated blood products.MethodsWe asked 444 Japanese centers that specialize in treating HIV patients for participation, whether they have HIV/HCV coinfected cases with HCC, and the patient characteristics, treatments for HCC and survival after treatments were retrospectively reviewed according to each institutional medical records.ResultsOf 444 centers, 139 centers (31%) responded to the first query, and 8 centers (1.8%) ultimately provided 26 cases of HCC in coinfected hemophilic patients, diagnosed between December 1999 and December 2017. All 26 were male hemophilic patients, with a median age at HCC diagnosis of 49 (range, 34–73) years. Thirteen cases (50%) were HCV-RNA positive, and 14 cases (54%) had a solitary tumor. Even in the cases of Child-Pugh grade A, only 1 case underwent resection, and 18 cases (69%) did not receive the standard treatment recommended by the Japanese Society of Hepatology.ConclusionsHemophilic HCC patients with HIV/HCV coinfection may not routinely receive standard treatment due to their bleeding tendency and several complications related to HIV/HCV coinfection.     

Radiosynoviorthesis of knees by means of 166Ho-holmium-boro-macroaggregates

The aim of this study was to evaluate adverse and therapeutic effects of applicated holmium-boro-macroaggregates (HBMAs) in the radiosynoviorthesis (RSO) of knees in patients suffering from chronic synovitis. We started RSO of the knees by means of a new radiopharmaceutical (RF) HBMA in patients with gonarthrosis, rheumatoid arthritis, chronic synovitis, psoriatic arthritis, and gout arthropathy. Seventeen (17) intra-articular injections were performed in 15 patients who were receiving a mean activity of 972 MBq (range, 904-1057) of 166Ho-HBMA. Patient inclusion to the study followed a series of inclusion and exclusion criterions. The patients were hospitalized for 3 days. Side-effects were evaluated during their hospital stay and again after 6-8 weeks. Static scintigraphy of knee joints and measurements of blood radioactivity were performed. Therapeutic effects were evaluated after 6-8 weeks and at 6 months. In 2 hours and 2 days following the application, we proved, by means of knee and inguinal scintigraphy, only insignificant radiopharmaceutical leakage from the joint cavity to the inguinal lymph nodes in 4 patients. In the treated patients, no serious adverse effects occurred. Nine (9) patients were without complaints, 4 patients had slight knee exudation, and 2 patients had great exudation. Therapeutic effects were as follows: 2 patients were without pain, 9 were with lower pain, 3 were with the same pain, and 1 patient was with increased pain. Joint motion was improved in 7 patients, remained the same in 7 patients, and was impaired in 1 patient. Analgesics consumption was lower in 5 patients, the same in 9 patients, and greater in 1 patient. Knee exudation was absent in 2 patients, lower in 4 patients, the same in 6 patients, and greater in 3 patients. In 3 patients it was necessary to do surgical RSO. This RF can extend the range of clinically used radiopharmaceuticals for RSO and to supplement space between 90Y with high energy and 186Re with 169Er with lower beta energy. The energy of 166Ho is suitable for great and medium joints (i.e., knees, hips, shoulders, elbows, wrists, and ankles).     

Extra-articular wide tumor resection and limb reconstruction in malignant bone tumors invading the knee joint

We demonstrate our procedure of extra-articular wide tumor resection and its clinical outcome. The knee joint including the femorotibial, patellofemoral and the proximal tibiofibular joints was totally resected without any view of articular cartilage and synovium. The resected limb was reconstructed with endoprosthesis of the knee joint. The average score of the limb function evaluated by ISOLS criteria was 69.3% in all patients. The limb function of these patients was almost the same as that of the patients who received the intra-articular procedure. The procedure of extra-articular resection was theoretically necessary and clinically practical.     

MicroRNA profiling in locally advanced esophageal cancer indicates a high potential of miR‐192 in prediction of multimodality therapy response

To identify possible predictive markers, our study aimed to characterize microRNA (miRNA) profiles of responder and nonresponder in the multimodality therapy of locally advanced esophageal cancer. Initially, a microarray‐based approach was performed including eight patients with esophageal cancer. Patients received neoadjuvant chemoradiation followed by surgical resection. Major histopathological response was defined if resected specimens contained less than 10% vital tumor cells (major/minor response: 4/4 patients). Intratumoral RNA was isolated from both, pretherapeutic tissue biopsies in addition to corresponding surgical specimens. The profile of 768 miRNAs was analyzed in 16 specimens (preneoadjuvant and postneoadjuvant therapy). Selected miRNAs were than analyzed on pretherapeutic and post‐therapeutic biopsies of 80 patients with esophageal cancer, who underwent multimodality therapy (major/minor response: 30/50 patients). Comprehensive miRNA profiling identified miRNAs in pretherapeutic biopsies that were significantly different between major/minor responders. Based on the microarray results, miR‐192, miR‐194 and miR‐622 were selected and the dysregulated miRNAs were studied on an extended series of esophageal cancer patients. The expression of miR‐192, miR‐194 and miR‐622 was significantly reduced after neoadjuvant therapy confirming the array profiling data. Importantly, the pretherapeutic intratumoral expression of miR‐192 and miR‐194 was significantly associated with the histopathologic response of esophageal squamous cell carcinoma to multimodal therapeutic treatment. Therefore, in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation followed by esophagectomy, miR‐192 and miR‐194 in pretherapeutic biopsies are considered as indicators of major histopathologic regression.     

Tumor angiogenesis of low-grade astrocytomas measured by dynamic susceptibility contrast-enhanced MRI (DSC-MRI) is predictive of local tumor control after radiation therapy

PURPOSE: To assess regional cerebral blood volume (rCBV) as a surrogate marker of angiogenesis in patients with low-grade fibrillary astrocytoma before radiation therapy and to correlate measured values with clinical outcome after fractionated stereotactic radiotherapy (FSRT). METHODS: Twenty-five patients with histologically proven fibrillary astrocytomas were examined using dynamic susceptibility contrast-enhanced MRI before radiotherapy. Radiotherapy was delivered to mean and median total doses of 60.9 and 60 Gy, respectively (range 55.8-66 Gy). During MRI for treatment planning, 55 T2*-weighted gradient echo images were acquired before, during, and after i.v. contrast-bolus injection. The acquired signal-time curves were converted into concentration-time curves. By normalization to an arterial input function, absolute and relative rCBV values were calculated. Measured pretherapeutic rCBV data were correlated to outcome in terms of local control after FSRT. RESULTS: Mean pretherapeutic rCBV for astrocytomas was 6.5 +/- 3.7 ml/100 g tissue. Mean and median follow-up times were 47.8 and 52 months, respectively. Fifteen tumors recurred during the period, with a mean and median latency of 39.1 and 42 months, respectively. Tumors recurring earlier than 42 months after FSRT showed a higher pretreatment rCBV than tumors recurring later and tumors in continued local control (8.12 +/- 4.48 ml/100 g vs. 6.0 +/- 2.3 ml/100 g and 4.73 +/- 2.47 ml/100 g; p = 0.02 and p = 0.03). The respective ratios of tumor rCBV in early recurrent tumors to gray matter and white matter rCBV were 0.98 +/- 0.38 and 2.17 +/- 1.36 as compared with 0.79 +/- 0.14 and 1.44 +/- 0.29 in locally controlled tumors (p = 0.074 and p = 0.056). CONCLUSIONS: In fibrillary low-grade astrocytomas, a noninvasive assessment of angiogenesis as indicated by rCBV measurement was feasible. The present data suggest that high pretherapeutic angiogenic activity in low-grade astrocytomas indicates a subgroup of tumors at higher risk for early local recurrence or malignant transformation after FSRT.     

Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma

PURPOSE: The aim of our study was to correlate perfusion indices and apparent diffusion coefficients with therapy outcome after chemoradiation. METHODS AND MATERIALS: In 34 patients with primary rectal carcinoma (cT3) undergoing preoperative chemoradiation, pretherapeutic perfusion indices and apparent diffusion coefficients were obtained by dynamic or diffusion-weighted magnetic resonance imaging. Therapy response was defined if the pathologic observation revealed no invasion into the perirectal fat after chemoradiation. RESULTS: In 18 patients, a response and in 16, no response was observed. Statistically significant differences were found for the mean perfusion index (p < 0.001; 7.5 +/- 1.5 mL/min/100 g vs. 10.7 +/- 2.7 mL/min/100 g) and for the intratumoral cumulative fraction of pixels with perfusion-indices > 12 mL/min/100 g (p < 0.001, 3.7 +/- 4.0% vs. 24.7 +/- 17.9%). A three-way ANOVA resulted in significant effects for therapy responder/nonresponder (p < 0.001) and for apparent diffusion coefficient and the individual patients. CONCLUSION: Perfusion indices and apparent diffusion coefficients inside the tumor region seem to be of predictive value for therapy outcome of preoperative therapy in patients with primary rectal carcinoma. Higher parameter levels in the nonresponding group could be explained by increased shunt flow or increased angiogenic activity in aggressive tumor cell clusters resulting in reduced nutrients supply and higher fraction of intratumoral necrosis respectively.     

Prognostic relevance of oncological serum biomarkers in liver cancer patients undergoing transarterial chemoembolization therapy

As transarterial chemoembolization (TACE) therapy is an effective locoregional treatment for patients with advanced liver cancer, prognostic biomarkers are highly needed for pretherapeutic stratification of patients to TACE therapy. Sera of 50 prospectively and consecutively included patients with hepatocellular carcinoma (HCC) undergoing TACE were taken before and 24 h after TACE application. Levels of liver-specific, tumor-related, and cell death biomarkers were analyzed and correlated with overall patient survival. The study was particularly focused on patients treated by TACE with palliative intention (N = 38). Sixteen of 38 patients died within 1 year after TACE, 22 were still alive. In univariate analysis, high levels of cytokeratin 19-fragments (CYFRA 21-1), alpha fetoprotein (AFP), and low choline esterase (CHE) levels measured before and 24 h after TACE were correlated with unfavorable outcome. Further high pretherapeutic lactate dehydrogenase (LDH), aspartate-aminotransferase, and bilirubin levels as well as high 24 h C-reactive protein values were associated with poor survival. In multivariate analysis of clinical and only pretherapeutic biomarkers, AFP, CHE, and LDH showed to be independent prognostic parameters. When additionally 24 h values were included, CHE (24 h) and AFP (24 h) were the strongest independent prognostic biomarkers with a slightly higher prognostic power (Akaike’s information criterion 90.3 vs. 92.7). The combination of AFP, CHE, and LDH enables efficient pretherapeutic stratification of HCC patients in advanced tumor stage for TACE therapy.     

Rectal bleeding after hypofractionated radiotherapy for prostate cancer: correlation between clinical and dosimetric parameters and the incidence of grade 2 or worse rectal bleeding

PURPOSE: To investigate the incidence and severity of rectal bleeding after high-dose hypofractionated radiotherapy (RT) for prostate cancer, and to explore the factors affecting the incidence of Grade 2 or worse rectal bleeding. METHODS AND MATERIALS: The data of 52 patients who had been treated by external beam RT for localized prostate cancer between 1999 and 2002 were analyzed. All the patients had received hypofractionated external beam RT to a total dose of 69 Gy in 3-Gy fractions, three fractions weekly. The clinical and dosimetric factors affecting the incidence of Grade 2 or worse late rectal bleeding were analyzed by univariate and multivariate analyses. The effect of the percentage of the whole rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose (V(30), V(50), V(80), and V(90), respectively) on the incidence of rectal bleeding was evaluated. RESULTS: Of the 52 patients, 13 (25%) developed Grade 2 or worse rectal bleeding. One patient who needed laser coagulation and blood transfusion for the treatment of rectal bleeding was classified as having Grade 3 rectal bleeding. The median time to the development of Grade 2 or worse rectal bleeding was 11 months. The results of the univariate analysis revealed that the presence of a history of diabetes mellitus (p < 0.001), and V(30) >/= 60%, V(50) >/= 40% (p < 0.05), V(80) >/= 25%, and V(90) >/= 15% (p < 0.001) were statistically significant risk factors for the occurrence of Grade 2 or worse rectal bleeding. The results of the multivariate analysis revealed that a history of diabetes mellitus was the most statistically significant risk factor for the occurrence of rectal bleeding after hypofractionated RT for prostate cancer (p < 0.05). CONCLUSION: A history of diabetes mellitus was the most statistically significant risk factor for the occurrence of Grade 2 or worse rectal bleeding after high-dose hypofractionated RT, although dosimetric factors were also closely associated with the risk of rectal bleeding.     

Significant correlation between rectal DVH and late bleeding in patients treated after radical prostatectomy with conformal or conventional radiotherapy (66.6-70.2 Gy)

PURPOSE: Investigating the correlation between dosimetric/clinical parameters and late rectal bleeding in patients treated with adjuvant or salvage radiotherapy after radical prostatectomy. METHODS AND MATERIALS: Data of 154 consecutive patients, including three-dimensional treatment planning and dose-volume histograms (DVHs) of the rectum (including filling), were retrospectively analyzed. Twenty-six of 154 patients presenting a (full) rectal volume >100 cc were excluded from the analysis. All patients considered for the analysis (n = 128) were treated at a nominal dose equal to 66.6-70.2 Gy (ICRU dose 68-72.5 Gy; median 70 Gy) with conformal (n = 76) or conventional (n = 52) four-field technique (1.8 Gy/fr). Clinical parameters such as diabetes mellitus, acute rectal bleeding, hypertension, age, and hormonal therapy were considered. Late rectal bleeding was scored using a modified Radiation Therapy Oncology Group scale, and patients experiencing >or=Grade 2 were considered bleeders. Median follow-up was 36 months (range 12-72). Mean and median rectal dose were considered, together with rectal volume and the % fraction of rectum receiving more than 50, 55, 60, and 65 Gy (V50, V55, V60, V65, respectively). Median and quartile values of all parameters were taken as cutoff for statistical analysis. Univariate (log-rank) and multivariate (Cox hazard model) analyses were performed. RESULTS: Fourteen of 128 patients experienced >or=Grade 2 late bleeding (3-year actuarial incidence 10.5%). A significant correlation between a number of cutoff values and late rectal bleeding was found. In particular, a mean dose >or=54 Gy, V50 >or=63%, V55 >or=57%, and V60 >or=50% was highly predictive of late bleeding (p or=63% and those with V50 <63% (DVH grouping), data were fitted with a Cox regression hazard model using DVH grouping, rectal volume, and the main clinical parameters as independent variables. Results of the analysis showed that DVH grouping (relative risk 3.3; p = 0.04) and acute bleeding (relative risk 7.1; p = 0.001) are independently predictive of late bleeding. CONCLUSIONS: DVHs of the rectum are significantly correlated with late bleeding for patients irradiated at 66.6-70.2 Gy after radical prostatectomy.