Radiobiological analysis of preliminary results of a phase II study of pelvic hypofractionated and accelerated radiotherapy for high-risk prostate cancer patients.

PURPOSE: Conventionally fractionated radiotherapy (CRT) is widely applied for the treatment of high-risk prostate cancer. Pelvic node irradiation improves control of the disease. Although the therapeutic guidelines support the use of hypofractionated and accelerated radiotherapy (HypoAR), this is addressed to prostate and seminal vesicles. At the same time, the safety and efficacy of HypoAR for pelvic node irradiation remain obscure. Material and Methods: In a phase II study, we evaluated the feasibility of pelvic HypoAR in 22 high-risk prostate cancer patients. The RT scheme delivers 14 consecutive fractions of 3.67 Gy (total 51.38 Gy) to the prostate, 3.5 Gy (total 49 Gy) to the seminal vesicles, and 2.7 Gy (total 37.8 Gy) to the lymph nodes, using image-guided volumetric modulated arc therapy. A comparative radiobiological analysis of dose-volume histogram is performed (HypoAR vs. hypothetical equivalent CRT regimens, without and with time correction). RESULTS: Our clinical experience shows impressively low early and short-term late toxicities, without any grade III events, within a median follow-up of 30 months. Only one biochemical relapse was recorded 30 months after irradiation. In radiobiological analysis, considering an α/ß-value of 4 Gy and a λ-value of 0.2 Gy/day for late effects, all comparisons predicted significantly lower toxicity for the HypoAR regimen (p < 0.05). For early toxicities (α/ß = 10 Gy), a λ-value lower than 0.4 Gy/day favors the HypoAR regimen, which is along with the clinical results. CONCLUSION: Radiobiological analysis favors HypoAR as a safe and effective regimen for high-risk prostate cancer patients, which is confirmed in the current phase II clinical study.

Comparative radiobiological analysis and preliminary results of Ultra hypofractionated accelerated radiotherapy for low-risk prostate cancer patients.

PURPOSE: Moderately accelerated hypofractionation (HypoAR) has been recently established as a standard radiotherapy scheme for low-risk prostate cancer. The application of ultra-hypofractionated regimens (ultra-HypoAR), with fraction size above 5 Gy, is also widely tested. METHODS: We applied Image Guided Radiation Therapy (IGRT) ultra-HypoAR delivered with Volumetric Modulated Arc Therapy (VMAT) technique in low-risk prostate cancer patients (5.75 Gy/fraction, 40.25 Gy total dose, two fractions per week). A comparative radiobiological analysis of Dose-Volume Ηistograms (DVH) obtained for target volumes and organs at risk was performed, investigating the advantages and disadvantages of ultra-HypoAR and conventional radiotherapy regimens (CRT). Early clinical results on efficacy and toxicity are also reported. RESULTS: We calculated the Normalized Total Dose (NTD) and NTD with time correction (NTD_T)-based biological Dose- Volume Histograms (bDVH) for bladder and rectum tissue late effects (α/ß=4 Gy) and early effects (α/ß=10 Gy). Ultra-HypoAR produced a significantly lower biological dose burden than CRT, for both early and late responding tissue components of the bladder and rectum, whether calculated for time-correction or not (p<0.0001). Our clinical experience showed that the ultra-HypoAR regimen produced minimal early and late radiation sequelae. The median PSA levels dropped from 9.1 to 0.75 and 0.45 ng/ml at 6 and 12 months, respectively, after the end of therapy. CONCLUSIONS: In conclusion, radiobiological analysis of DVHs and preliminary clinical experience predict a better efficacy and low early and late toxicity profile for the tested seven-fraction VMAT ultra-HypoAR regimen with IGRT.

Reversible posterior leukoencephalopathy syndrome induced by pazopanib.

BACKGROUND: The reversible posterior leukoencephalopathy syndrome is a clinical/radiological syndrome characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging findings. There are several reports in the literature that depict its occurrence in cancer patients. The list of common anticancer and supportive care drugs that predispose to reversible posterior leukoencephalopathy syndrome is expanding and includes not only a large number of chemotherapeutic agents but also an increased number of new targeted drugs, particularly angiogenesis inhibitors such as bevacizumab,sorefenib and sunitinib. Pazopanib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit which after a positive phase III randomized clinical trial in patients with advanced renal cell cancer received FDA approval for the treatment of advanced renal cell carcinoma. Until now no cases of reversible posterior leukoencephalopathy syndrome induced by pazopanib have been reported. CASE REPORT: We present the case of a 40 years old female patient with heavily pre-treated metastatic renal cell carcinoma who received pazopanib as salvage treatment. After 21 days of pazopanib therapy the patient referred to the emergency department with epileptic seizure, impaired vision at both eyes and headache. MRI of the brain revealed subcortical oedema at the occipital and parietal lobes bilaterally. She was treated with anticonvulsants, i.v. administration of mannitol and antihypertensives and she recovered completely from her symptoms and was discharged on the tenth hospital day. A brain MRI performed 3 weeks after showed that the subcortical oedema had been subsided. CONCLUSION: In conclusion this is the first case of pazopanib induced reversible posterior leukoencephalopathy syndrome. Although usually reversible, this syndrome is a serious and potentially life threatening adverse effect, if untreated, that should be considered by physicians treating metastatic renal cell carcinoma patients with pazopanib.

Unusual malpositioning of hemodialysis catheter into the hepatic veins.

Malpositioning of long-term hemodialysis catheter is a known complication that may lead to a gradual decline in blood flow. We report two rare catheter malpositions in the hepatic veins in two patients with end-stage renal disease in whom a dialysis catheter was inserted through the left external jugular vein and the right external jugular vein. Because of gradual reduction of catheters' blood flow, an angiography was performed, which confirmed catheters' tip positioning into the hepatic veins. The catheters were replaced in the correct site.

Is Post-ERCP Pancreatitis a Genetically Predisposed Complication?

Background/Objectives. Pancreatitis remains the most common complication of ERCP. History of post-ERCP pancreatitis is an independent risk factor for a new episode, suggesting a genetic background. The N34S mutation in serine protease inhibitor Kazal type 1 (SPINK 1) gene may downregulate the threshold for the development of pancreatitis. The aim of the present study is to evaluate the presence of this mutation among patients with post-ERCP pancreatitis. Methods. During a period of four years, thirty patients with post-ERCP pancreatitis entered the study. Patients and procedural data were collected, focusing on risk factors for pancreatitis. Blood samples were taken for genetic testing for the presence of N34S mutation in SPINK 1 gene. After DNA extraction, we used an allele-specific polymerase chain reaction as an initial screening method for the N34S mutation, and in order to confirm the results and to determine the hetero- and homozygosity genotype status, we used a restriction fragment length polymorphism (RFLP) method. Results. None of the thirty patients was found to carry the N34S mutation, with both of the applied methods. Patients had an average of two of the known risk factors. Conclusion. SPINK1 N34S mutation does not seem to play a role in post-ERCP pancreatitis, but larger studies needed to confirm our results.

Complete response after sorafenib therapy for hepatocellular carcinoma in an HIV-HBV co infected patient: Possible synergy with HAART ? A case report.

A significant proportion of HIV patients, ranging between 5-67%, are co-infected with hepatitis B virus (HBV). Several studies suggest an increasing incidence of hepatocellular carcinoma (HCC) in HIV infected individuals. We report the case of a 69 years old male co infected with HBV and HIV who developed HCC. The patient was unfit for curative approach and he underwent three sessions of transcatheter arterial chemoembolisation (TACE). After the last session the disease assessment showed progression and sorafenib therapy was initiated. Highly active antiretroviral therapy (HAART) was continued during sorafenib treatment. The patient achieved a radiological complete response (CR) after 6 months of therapy and remained with no sign of HCC progression at subsequent assessment. Meanwhile, patient's HIV and HBV infections remained stable. Regarding toxicity the patient developed grade 3 hand foot skin reaction (HFSR) that required 50% dose reduction of sorafenib, grade 3 hypertension and grade 2 diarrhea. In conclusion this is the first case of successful treatment of HCC in a HIV-HBV co-infected patient and only the second report of the co administration of sorafenib with HAART.

Percutaneous nephrolithotomy in a patient with intrarenal arterial aneurysm.

We report the case of a male patient with a left renal pelvic stone 2.5 cm in maximum diameter and a large upper pole intrarenal arterial aneurysm on the same side. The stone was treated with percutaneous nephrolithotomy (PCNL). This procedure was feasible even in this difficult clinical setting. Puncture of a calyx located at a safe distance from the aneurysm and meticulous surgical technique were essential in realizing the best possible outcome. To our knowledge, this is the first case of PCNL performed on a patient with a renal stone and an intrarenal arterial aneurysm.

Endoscopic removal of a toothpick perforating the sigmoid colon and causing chronic abdominal pain: a case report.

Toothpick ingestion is implicated in gut injuries which may cause severe complications, mimicking diseases causing acute abdomen. However, toothpick ingestion-related perforation may also cause mild, non-specific gastrointestinal symptoms without significant findings or major complications. We describe a young male with chronic postprandial lower abdominal pain caused by a toothpick impaction at the rectosigmoid junction after inadvertent ingestion. The foreign body was detected and successfully removed during flexible sigmoidoscopy. Perforation due to foreign body ingestion must be considered in the differential diagnosis in patients presenting with unexplained symptoms and findings, even when they do not recall any foreign body ingestion.

Liver regeneration following radiofrequency ablation.

BACKGROUND: Radiofrequency ablation (RFA) of the liver leads to reduction of liver parenchymal volume. We sought to evaluate the regenerative response of the liver following RFA. MATERIALS AND METHODS: Thirty healthy New Zealand white rabbits were subjected to a single session liver RFA using a cool-tip electrode after midline laparotomy. The regenerative process of the liver was assessed at various time-points (0 h, 48 h, 1 wk, 3 wk, 10 wk) in terms of computed tomography-based liver volume measurements, histological examination, hepatocyte mitotic activity, and serum biochemistry. RESULTS: According to computed tomography-measurements, intact liver volume was gradually restored to the initial liver volume by the 10th week, while liver ablated volume was confined down to 50% of the initial ablated volume. At histology, inflammation, edema, and hepatocellular necrosis in the intact liver parenchyma, noted at 48 h, started to regress by 1 wk. Mitotic activity, initiated by 48 h, was substantially increased at 1 wk and remained high up to the 10th week. Serum transaminase levels were elevated up to 1 wk. CONCLUSIONS: Liver RFA triggers a slow but sustained regenerative response of the liver with subsequent delayed restoration of parenchymal volume, while the ablated volume is gradually condensed.

Reversal of deep vein reflux after successful stenting in a patient with venous hypertension after thigh access graft creation.

Presented here is a case of reversal of deep vein reflux after successful stenting in a patient with venous hypertension and valve incompetence after thigh angioaccess creation. The patient with exhausted upper-extremity access sites underwent a loop graft in the upper thigh. Six months later, the patient developed leg edema and significant femoral vein reflux on duplex ultrasound. Fistulography revealed an iliac vein stenosis, which was treated successfully with stenting. The edema and reflux on duplex promptly resolved. In similar cases, reflux may be a consequence of functional valve incompetence and can be reverted by timely treating the underlying stenosis.

Bone mass, gonadal function and biochemical assessment in young men with trisomy 21.

OBJECTIVE: The objective of the study was to find out whether biochemical and hormonal profile of sexual function and mineral metabolism are related to low bone mass in young men with Down syndrome. STUDY DESIGN: Eleven young men with trisomy 21 (mean age 26.45 years) and 12 healthy university students of similar age, participated in the study. The bone mineral density (BMD) of the lumbar vertebrae was measured in posteroanterior (PA) projection. Sexual development was assessed by clinical examination. The levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone sulfate (DHEA-S), 17-OH progesterone and parathormone (PTH) were measured accordingly by radioimmunoassay. Serum calcium (Ca) and phosphate (P) as well as fasting urinary Ca and hydroxyproline (OHP) were also measured. RESULTS: BMD in DS patients was significantly lower (P<0.001) compared to their control counterparts. No significant differences were observed in mean concentrations of FSH, testosterone and DHEA-S, while LH and 17-OH progesterone levels were significantly higher in DS compared to control group (P<0.01 and <0.05, respectively). Serum Ca and P and urine Ca/Creat ratio did not differ between groups. OHP/Creat ratio was significantly higher in DS patients. PTH levels were extremely low (1pmol/l) in two patients. CONCLUSIONS: The findings of this study show decreased bone mass in subjects with DS. Factors, possibly related to low bone mass, are some degree of hypogonadim, hypotonia, low muscular strength and immobility. The findings suggest further research on the biochemistry and endocrinology of bone metabolism in patients with trisomy 21.