Salvage Radiotherapy After Radical Prostatectomy

Salvage radiation therapy is the sole curative treatment for patients experiencing biochemical relapse after radical surgical treatment of prostate cancer. The main dilemma in salvage radiation therapy is, whether or not biochemical relapse represents purely localized recurrent disease in the prostatic fossa or systemic micrometastasis. Initiating salvage radiation therapy at an early time point raises its chances of success, but may lead to overtreatment of patients. Target volume definition and treatment techniques are a matter of current research, with still many questions unanswered. Strategies of treatment escalation either by increasing the treatment dose or combining radiation therapy with androgen deprivation therapy are being addressed in clinical trials.

Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10

PURPOSE Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification. PATIENTS AND METHODS Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25. RESULTS Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02). CONCLUSION Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.

MRI of hip osteoarthritis and implications for surgery

Osteoarthritis of the hip joint is caused by a combination of intrinsic factors and extrinsic factors. Different surgical techniques are being performed to delay or halt osteoarthritis. Success of salvage procedures of the hip depends on the existing cartilage and joint damage before surgery; the likelihood of therapy failure rises with advanced osteoarthritis. For imaging of intra-articular hip pathology, MR imaging represents the best technique because of its ability to directly visualize cartilage, superior soft tissue contrast, and the prospect of multidimensional imaging. This article gives an overview on the standard MR imaging techniques used for diagnosis of hip osteoarthritis and their implications for surgery.

Outcomes of patients on dual-boosted PI regimens: experience of the Swiss HIV cohort study

Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks. 295 patients (72.5%) were on DBPI for over 6 months. The median duration was 2.2 years. Of 287 patients who had HIV-RNA >400?copies/ml at the start of the regimen, 184 (64.1%) were ever suppressed while on DBPI and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% confidence interval 90-125 days). The median number of past regimens was 6 (IQR, 3-8). The main reasons for discontinuing the regimen were patient's wish (48.3%), treatment failure (22.5%), and toxicity (15.8%). Acquisition of HIV through intravenous drug use and the use of lopinavir in combination with saquinavir or atazanavir were associated with an increased likelihood of suppression within 6 months. Patients on DBPI are heavily treatment experienced. Viral suppression within 6 months was achieved in more than half of the patients. There may be a place for DBPI regimens in settings where more expensive alternates are not available.

Proximal row carpectomy in emergency

Proximal row carpectomy (PRC) is a well-accepted procedure for the treatment of early post-traumatic degenerative disease of the wrist. Much less frequently, PRC has been advocated as an emergency procedure for irreparable fracture-dislocation of the wrist. Our objective was to compare the results of PRC in patients having undergone this procedure in the two contexts. We conducted a retrospective analysis of the clinical and radiographic results of six patients treated by emergency PRC as compared to six patients who underwent elective PRC. The mean follow-up was 36 months. Both the patient's satisfaction and the grasp of the wrist joint were significantly better in patients who underwent PRC emergency as compared to those having undergone elective PRC. Quick DASH score, radiographic results, and return to work were also more favourable in these patients, but the difference between the two groups was not significant. This study confirms that PRC is a valuable salvage technique indicated in early posttraumatic wrist collapse. Moreover, when performed in emergency, the procedure shows even better subjective and objective results, allowing a majority of patients to return to their previous job.

Endovascular Revascularization of Below-the-Knee Arteries: Prospective Short-Term Angiographic and Clinical Follow-up

PURPOSE: To evaluate arterial lesion characteristics and their impact on angiographic and clinical outcomes after endovascular below-the-knee (BTK) revascularization. MATERIALS AND METHODS: Between April 2008 and June 2009, 33 patients (mean age 74.9 years) with 34 limbs and 50 arterial segments (mean lesion length 59.3 mm) undergoing endovascular BTK revascularization agreed to undergo prospective clinical and intraarterial angiographic 6-month follow-up evaluation. Clinical indication for BTK revascularization was critical limb ischemia (CLI) in 18 patients and delayed wound healing without hemodynamic evidence of CLI and intermittent claudication (IC) in 15 patients. RESULTS: Binary restenosis was observed in 40% of treated segments at 6 months. Primary sustained clinical improvement was 82.4% and 55.9% at 3 months and 6 months. Lesion length was independently associated with binary restenosis (hazard ratio [HR] 1.013, 95% confidence interval [CI] 1.000-1.016, P = .05) and lower rates of primary sustained clinical improvement (HR 1.024, 95% CI 1.006-1.042, P = .008). CONCLUSIONS: Endovascular BTK revascularization yields clinical and angiographic benefits both for patients with IC and for patients with CLI. Although arterial lesion length adversely affects angiographic and clinical outcomes after endovascular revascularization, limb salvage rates were substantially higher compared with the comparatively low patency rates after BTK angioplasty.

Basilar artery occlusion

The clinical presentation of basilar artery occlusion (BAO) ranges from mild transient symptoms to devastating strokes with high fatality and morbidity. Often, non-specific prodromal symptoms such as vertigo or headaches are indicative of BAO, and are followed by the hallmarks of BAO, including decreased consciousness, quadriparesis, pupillary and oculomotor abnormalities, dysarthria, and dysphagia. When clinical findings suggest an acute brainstem disorder, BAO has to be confirmed or ruled out as a matter of urgency. If BAO is recognised early and confirmed with multimodal CT or MRI, intravenous thrombolysis or endovascular treatment can be undertaken. The goal of thrombolysis is to restore blood flow in the occluded artery and salvage brain tissue; however, the best treatment approach to improve clinical outcome still needs to be ascertained.

Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma

Purpose To evaluate the efficacy and toxicity of stereotactic fractionated radiotherapy (SFRT) for patients with pituitary macroadenoma (PMA). Methods and Materials Between March 2000 and March 2009, 27 patients (male to female ratio, 1.25) with PMA underwent SFRT (median dose, 50.4 Gy). Mean age of the patients was 56.5 years (range, 20.3 - 77.4). In all but one patient, SFRT was administered for salvage treatment after surgical resection (transphenoidal resection in 23, transphenoidal resection followed by craniotomy in 2 and multiple transphenoidal resections in another patient). In 10 (37%) patients, the PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone-secreting and 2 multiple hormone-secretion). Three (11.1%) and 9 (33.3%) patients had PMA abutting and compressing the optic chiasm, respectively. Mean tumor volume was 2.9 ± 4.6 cm3. Eighteen (66.7%) patients had hypopituitarism prior to SFRT. The mean follow-up period after SFRT was 72.4 ± 37.2 months. Results Tumor size decreased for 6 (22.2%) patients and remained unchanged for 19 (70.4%) other patients. Two (7.4%) patients had tumor growth inside the prescribed treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT. Biochemical remission occurred in 3 (30%) patients with functional PMA. Two patients with normal anterior pituitary function before SFRT developed new deficits 25 and 65 months after treatment. The 5-year survival without new anterior pituitary deficit was thus 95.8%. Five patients with visual field defect had improved visual function and 1 patient with no visual defect prior to SFRT, but an optic chiasm abutting tumor, had a decline in visual function. The estimated 5-year vision and pituitary function preservation rates were 93.2% and 95.8%, respectively. Conclusions SFRT is a safe and effective treatment for patients with PMA, although longer follow-up is needed to evaluate long-term outcomes. In this study, approximately 1 patient with visual field defect out of two had an improved visual function.

Chapter IV: Treatment of critical limb ischaemia

Recommendations stated in the TASC II guidelines for the treatment of peripheral arterial disease (PAD) regard a heterogeneous group of patients ranging from claudicants to critical limb ischaemia (CLI) patients. However, specific considerations apply to CLI patients. An important problem regarding the majority of currently available literature that reports on revascularisation strategies for PAD is that it does not focus on CLI patients specifically and studies them as a minor part of the complete cohort. Besides the lack of data on CLI patients, studies use a variety of endpoints, and even similar endpoints are often differentially defined. These considerations result in the fact that most recommendations in this guideline are not of the highest recommendation grade. In the present chapter the treatment of CLI is not based on the TASC II classification of atherosclerotic lesions, since definitions of atherosclerotic lesions are changing along the fast development of endovascular techniques, and inter-individual differences in interpretation of the TASC classification are problematic. Therefore we propose a classification merely based on vascular area of the atherosclerotic disease and the lesion length, which is less complex and eases the interpretation. Lesions and their treatment are discussed from the aorta downwards to the infrapopliteal region. For a subset of lesions, surgical revascularisation is still the gold standard, such as in extensive aorto-iliac lesions, lesions of the common femoral artery and long lesions of the superficial femoral artery (>15 cm), especially when an applicable venous conduit is present, because of higher patency and limb salvage rates, even though the risk of complications is sometimes higher than for endovascular strategies. It is however more and more accepted that an endovascular first strategy is adapted in most iliac, superficial femoral, and in some infrapopliteal lesions. The newer endovascular techniques, i.e. drug-eluting stents and balloons, show promising results especially in infrapopliteal lesions. However, most of these results should still be confirmed in large RCTs focusing on CLI patients. At some point when there is no possibility of an endovascular nor a surgical procedure, some alternative non-reconstructive options have been proposed such as lumbar sympathectomy and spinal cord stimulation. But their effectiveness is limited especially when assessing the results on objective criteria. The additional value of cell-based therapies has still to be proven from large RCTs and should therefore still be confined to a research setting. Altogether this chapter summarises the best available evidence for the treatment of CLI, which is, from multiple perspectives, completely different from claudication. The latter also stresses the importance of well-designed RCTs focusing on CLI patients reporting standardised endpoints, both clinical as well as procedural.

Autologous peripheral blood stem cell transplantation for acute myeloid leukemia

We report the results of a prospective, randomized phase 3 trial evaluating autologous peripheral blood stem cell transplantation (ASCT) versus intensive consolidation chemotherapy in newly diagnosed AML patients in complete remission (CR1). Patients with AML (16-60 years) in CR1 after 2 cycles of intensive chemotherapy and not eligible for allogeneic SCT were randomized between intensive chemotherapy with etoposide and mitoxantrone or ASCT ater high-dose cyclophosphamide and busulfan. Of patients randomized (chemotherapy, n = 259; ASCT, n = 258), more than 90% received their assigned treatment. The 2 groups were comparable with regard to prognostic factors. The ASCT group showed a markedly reduced relapse rate (58% vs 70%, P = .02) and better relapse-free survival at 5 years (38% vs 29%, P = .065, hazard ratio = 0.82; 95% confidence interval, 0.66-1.1) with nonrelapse mortality of 4% versus 1% in the chemotherapy arm (P = .02). Overall survival was similar (44% vs 41% at 5 years, P = .86) because of more opportunities for salvage with second-line chemotherapy and stem cell transplantation in patients relapsing on the chemotherapy arm. This large study shows a relapse advantage for ASCT as postremission therapy but similar survival because more relapsing patients on the chemotherapy arm were salvaged with a late transplantation for relapse. This trial is registered at www.trialregister.nl as #NTR230 and #NTR291.

Rationales for the Bernese approaches in acetabular surgery

PURPOSE: To present two new approaches to acetabular surgery that were established in Berne, and which aim at enhanced visualization and anatomical reconstruction of acetabular fractures. METHOD: The trochanteric flip osteotomy allows for surgical hip dislocation, and was introduced as a posterior approach for acetabular fracture management involving the posterior column and wall. For acetabular fractures predominantly involving the anterior column and the quadrilateral plate, the Pararectus approach is described. RESULTS: Full exposure of the hip joint, as provided by the trochanteric flip osteotomy, facilitates anatomical reduction of acetabular or femoral head fractures and safe positioning of the anterior column screw in transverse or T-shaped fractures. Additionally, the approach enables osteochondral transplantation as a salvage procedure for severe chondral femoral head damage and osteoplasty of an associated inadequate offset at the femoral head-neck junction. The Pararectus approach allows anatomical restoration with minimal access morbidity, and combines advantages of the ilioinguinal and modified Stoppa approaches. CONCLUSIONS: Utilization of the trochanteric flip osteotomy eases visualization of the superior aspect of the acetabulum, and enables the evaluation and treatment of chondral lesions of the femoral head or acetabulum and labral tears. Displaced fractures of the anterior column with a medialized quadrilateral plate can be addressed successfully through the Pararectus approach, in which surgical access is associated with minimal morbidity. However, long-term results following the two presented Bernese approaches are needed to confirm that in the treatment of complex acetabular fractures the rate of poor results in almost one-third of all cases (as currently yielded using traditional approaches) might be reduced by the utilization of the presented novel approaches.

Postoperative radiotherapy after radical prostatectomy: indications and open questions

Biochemical relapse after radical prostatectomy occurs in approximately 15-40% of patients within 5 years. Postoperative radiotherapy is the only curative treatment for these patients. After radical prostatectomy, two different strategies can be offered, adjuvant or salvage radiotherapy. Adjuvant radiotherapy is defined as treatment given directly after surgery in the presence of risk factors (R1 resection, pT3) before biochemical relapse occurs. It consists of 60-64 Gy and was shown to increase biochemical relapse-free survival in three randomized controlled trials and to increase overall survival after a median followup of 12.7 years in one of these trials. Salvage radiotherapy, on the other hand, is given upon biochemical relapse and is the preferred option, by many centers as it does not include patients who might be cured by surgery alone. As described in only retrospective studies the dose for salvage radiotherapy ranges from 64 to 72 Gy and is usually dependent on the absence or presence of macroscopic recurrence. Randomized trials are currently investigating the role of adjuvant and salvage radiotherapy. Patients with biochemical relapse after prostatectomy should at the earliest sign of relapse be referred to salvage radiotherapy and should preferably be treated within a clinical trial.

Resuscitative emergency thoracotomy in a Swiss trauma centre

Resuscitative emergency thoracotomy (ET) is performed as a salvage manoeuvre for selected patients with trauma. However, reports from European trauma centres are scarce.

Debulking surgery in the setting of very high-risk prostate cancer scenarios

What's known on the subject? and What does the study add? Nowadays radical prostatectomy (RP) is considered an effective treatment in high-risk prostate cancer (PCa) and the indications for a surgical approach are expanding, even in cases of very high PSA or node-positive disease. We explored the outcomes of debulking surgery in the setting of these very high-risk PCa patients, in order to assess its feasibility. This review confirms the important role achieved by surgery in the complex setting of patients with very high-risk PCA. Excellent survival rates have been reported, even when PSA exceeds 100 ng/mL. The completion of RP with lymphadenectomy might give a survival benefit in patients who were found intraoperatively to be node-positive. Furthermore, salvage RP confirmed to be the most effective treatment option after RT failure. On the contrary, up-to-date surgery of isolated nodal recurrences has shown only little benefit. Finally, there is no evidence supporting the efficacy of debulking surgery in metastatic or in hormone-refractory tumours. An accurate selection of the patient is essential.