Evaluation of the learning curve for Thulium laser enucleation of the prostate in a contemporary cohort.

PURPOSE: To assess the learning curve of Thulium laser enucleation of the prostate (ThuLEP) of a single surgeon. METHODS: Hundred patients suffering from benign prostatic hyperplasia were treated by the same surgeon. In all cases, a well-trained urologist was present in the operating room. Patients urinary function was assessed preoperatively using the International Prostate Symptoms Score (IPSS), maximum flow rate and Post-Void Residual volume. Preoperative prostate volume was recorded. Enucleation and morcellation efficiency and complication rate were evaluated. Patients were divided into 5 cohorts of 20 consecutive cases to assess changes in outcomes through time. RESULTS: Mean age of patients was 73.1 years (SD 17.5) and mean prostate volume was 89.7 ml (SD 55.1). Overall, mean enucleation and morcellation efficiency were 1.7 (SD 2.9) and 5.1 (SD 2.7) g/min. A statistically significant increase in enucleation efficiency was observed when comparing cohort 1 vs 2 (0.9 vs 1.3 g/min, p = 0.03) and cohort 2 vs 3 (1.3 vs 1.7 g/min, p = 0.02). A statistically significant increase in morcellation efficiency was observed when comparing cohort 1 vs 2 (2.8 vs 3.7 g/min, p = 0.02) and cohort 2 vs 3 (3.7 vs 4.9 g/min, p = 0.03). In both cases, no significant differences were observed when comparing the following cohorts. Complication rate showed no significant differences throughout the caseload. CONCLUSIONS: In our single-surgeon experience, we observed a learning curve of nearly 60 cases for the ThuLEP procedure in presence of a well-trained surgeon. Complication rate was low from the beginning of surgical experience.

Pulsed-wave vs Continuous-wave Thulium Fiber Laser Enucleation of the Prostate (ThuFLEP): A Comparison of Perioperative Outcomes.

OBJECTIVE: To compare intra and early postoperative outcomes between pulsed-wave and continuous-wave Thulium Fiber Laser Enucleation of the Prostate (PW-ThuFLEP vs CW-ThuFLEP) for the treatment of benign prostatic hyperplasia. METHODS: 238 patients with lower urinary tract symptoms due to benign prostatic hyperplasia underwent PW-ThuFLEP (118 patients) vs CW-ThuFLEP (120 patients). Preoperative prostate volume, adenoma volume, prostate-specific antigen (PSA), and hemoglobin values were recorded. International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), post-void residual volume, and International Index of Erectile Function-5 score (IIEF-5) were assessed. Operative time, enucleation time, enucleation efficiency, catheterization time, irrigation volume, hospital stay, hemoglobin drop, and postoperative complications were recorded. Micturition improvements and sexual outcomes were evaluated 3months after surgery. RESULTS: CW-ThuFLEP showed shorter operative time (61.5 vs 67.4 minutes, P = .04). Enucleation time (50.2 vs 53.3 minutes, P = .12), enucleation efficiency (0.8 vs 0.7 g/min, P = .38), catheterization time (2.2 vs 2.1days, P = .29), irrigation volume (32.9 vs 32.8L, P = .71), hospital stay (2.8 vs 2.6days, P = .29) and hemoglobin drop (0.38 vs 0.39 g/dL, P = .53) were comparable. No significant difference in complication rate was observed. At 3-month follow-up, the procedures did not show any significant difference in IPSS, Qmax, post-void residual volume, IIEF-5, and PSA value. CONCLUSION: PW-ThuFLEP and CW-ThuFLEP both relieve lower urinary tract symptoms equally, with high efficacy and safety. Operative time was significantly shorter with CW-ThuFLEP, but with a small difference with low clinical impact. Enucleation time, enucleation efficiency, catheterization time, irrigation volume, hospital stay, hemoglobin and PSA drop, complication rate, and sexual outcomes showed no differences.

Dose mimicking based strategies for online adaptive proton therapy of head and neck cancer.

Objective.To compare a not adapted (NA) robust planning strategy with three fully automated online adaptive proton therapy (OAPT) workflows based on the same optimization method: dose mimicking (DM). The added clinical value and limitations of the OAPT methods are investigated for head and neck cancer (HNC) patients.Approach.The three OAPT strategies aimed at compensating for inter-fractional anatomical changes by mimiking different dose distributions on corrected cone beam CT images (corrCBCTs). Order by complexity, the OAPTs were: (1) online adaptive dose restoration (OADR) where the approved clinical dose on the planning-CT (pCT) was mimicked, (2) online adaptation using DM of the deformed clinical dose from the pCT to corrCBCTs (OADEF), and (3) online adaptation applying DM to a predicted dose on corrCBCTs (OAML). Adaptation was only applied in fractions where the target coverage criteria were not met (D98% < 95% of the prescribed dose). For 10 HNC patients, the accumulated dose distributions over the 35 fractions were calculated for NA, OADR, OADEF, and OAML.Main results.Higher target coverage was observed for all OAPT strategies compared to no adaptation. OADEF and OAML outperformed both NA and OADR and were comparable in terms of target coverage to initial clinical plans. However, only OAML provided comparable NTCP values to those from the clinical dose without statistically significant differences. When the NA initial plan was evaluated on corrCBCTs, 51% of fractions needed adaptation. The adaptation rate decreased significantly to 25% when the last adapted plan with OADR was selected for delivery, to 16% with OADEF, and to 21% with OAML. The reduction was even greater when the best plan among previously generated adapted plans (instead of the last one) was selected.Significance. The implemented OAPT strategies provided superior target coverage compared to no adaptation, higher OAR sparing, and fewer required adaptations.

Health-related quality of life and cognitive failures in patients with lower-grade gliomas treated with radiotherapy.

PURPOSE: Patients with lower grade (grade 2 and 3) glioma (LGG) frequently experience prolonged clinical course after multimodal therapy (including surgery, radiotherapy (RT), and chemotherapy). There is therefore significant concern about the potential long-term impact of the disease and treatments on quality of life (QOL) and cognitive functioning. In this context, we evaluated health related QOL and cognitive failures in LGG patients previously treated in our RT department. PATIENTS AND METHODS: Adult LGG patients previously treated with RT were prospectively included. Patients were evaluated based on standardized questionnaires [i.e., EORTC QLQ-C30, EORTC QLQ-BN20, and cognitive failures questionnaire (CFQ)]. RESULTS: Forty-eight patients were included. Median time elapsed since the end of RT was 59.5 months (range: 4-297). Based on EORTC QLQ-C30 and QLQ-BN20, the most prevalent HRQOL issues were impaired cognitive functioning (50% of the patients), impaired emotional functioning (47.9%), financial difficulties (43.7%), fatigue (43.7%), future uncertainty (39.6%), and impaired physical functioning (35.4%). Based on the CFQ, 35.4% of the patients showed increased tendency to cognitive failures. CONCLUSION: Patients with LGG frequently experience impairments in HRQOL and cognitive failures after treatment (including RT). Further efforts are therefore warranted to improve the QOL and cognitive outcome of these patients.

Repeat partial nephrectomy for recurrence of Von Hippel-Lindau-related renal cell carcinoma in an autotransplanted kidney.

Von Hippel-Lindau disease predisposes to develop renal cell carcinoma (RCC). Treatment is frequently challenging due to presence of bilateral tumors and high risk of recurrence. We present the case of a VHL-patient with bilateral recurrence of clear-cell RCC after bilateral partial nephrectomy and autotransplantation on one side. Recurrence on the transplanted kidney was treated with repeat partial nephrectomy with good oncological and functional outcomes. This approach is feasible in centres with wide experience in partial nephrectomy and renal transplantation when minimally invasive tumor ablation is not indicated.

Metabolic imaging in non-small-cell lung cancer radiotherapy.

Metabolic imaging by positrons emission tomography (PET) offers new perspectives in the field of non-small-cell lung cancer radiation therapy. First, it can be used to refine the way nodal and primary tumour target volumes are selected and delineated, in better agreement with the underlying tumour reality. In addition, the non-invasive spatiotemporal mapping of the tumour biology and the organs at risk function might be further used to steer radiation dose distribution. Delivering higher dose to low responsive tumour area, in a way that better preserves the normal tissue function, should thus reconcile the tumour radiobiological imperatives (maximising tumour local control) with dose related to the treatment safety (minimising late toxicity). By predicting response early in the course of radiation therapy, PET may also participate to better select patients who are believed to benefit most from treatment intensification. Altogether, these technological advances open avenues to in-depth modify the way the treatment plan is designed and the dose is delivered, in better accordance with the radiobiology of individual solid cancers and normal tissues.

Azathioprine and diffuse alveolar haemorrhage: the pharmacogenetics of thiopurine methyltransferase.

Current guidelines support the use of corticosteroids and azathioprine as one possible treatment strategy for idiopathic pulmonary fibrosis (IPF). However, some patients with genetic polymorphisms of thiopurine methyltransferase (TPMT) are at risk of severe azathioprine myelotoxicity. The current authors present the case of an 85-yr-old Caucasian male with IPF who developed diffuse alveolar haemorrhage as a complication of azathioprine-induced myelosuppression. Leukocyte genetic TPMT testing revealed that the patient had homozygous polymorphisms associated with the absence of TPMT activity and severe azathioprine-induced myelotoxicity. Thiopurine methyltransferase deficiency should be considered in patients who develop leukopenia early in treatment with azathiopurine, or who present with severe marrow suppression at usual doses. For centres with equipped laboratories, a dosing suggestion is provided based on thiopurine methyltransferase testing. Even with screening strategies, frequent monitoring of complete blood count and liver biochemistry should remain the mainstay of surveillance for azathioprine toxicity.

The gamma-2-herpesvirus bovine herpesvirus 4 causes apoptotic infection in permissive cell lines.

Increasing evidence suggests that regulation of apoptosis in infected cells is associated with several viral infections. The gammaherpesvirus bovine herpesvirus 4 (BHV-4) has been shown to harbor genes with antiapoptotic potentialities. However, here we have demonstrated that productive infection of adherent, permissive cell lines by BHV-4 resulted in a cytopathic effect characterized by induction of apoptosis. This phenomenon was confirmed using different techniques to detect apoptosis and using different virus strains and cell targets. Apoptosis induced by BHV-4 was inhibited by (1) treatment with doses of heparin, which completely inhibited virus attachment and infectivity; (2) UV treatment, which completely abrogated infectivity; and (3) treatment with a dose of phosphonoacetic acid, which blocked virus replication. Virus-induced apoptosis was associated with a down-regulation of Bcl-2 expression and was reduced by Z-VAD-FMK, but not by Z-DEVD-FMK (caspase-3-specific) caspase inhibitors. Inhibition of apoptosis by Z-VAD-FMK treatment during infection did not modify virus yield. Therefore, despite the presence of antiapoptotic genes in its genoma, BHV-4 could complete its cycle of productive infection while inducing apoptosis of infected cells. This finding might have implications for the pathobiology of BHV-4 and other gammaherpesviruses in vivo.