Comparison of oncological outcomes after segmental ureterectomy or radical nephroureterectomy in urothelial carcinomas of the upper urinary tract: results from a large French multicentre study

Study Type – Therapy (multi‐centre retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UUT‐UCs) are rare tumours. Because of the aggressive pattern of UC, radical nephroureterectomy (RNU) with bladder cuff removal remains the ‘gold‐standard’ treatment. However, conservative strategies, such as segmental ureterectomy (SU) or endourological management, have also been developed in patients with imperative indications. Some teams are now advocating the use of conservative management more commonly in cases of elective indications of UUT‐UCs. Due to the paucity of cases of UUT‐UC, only limited data are available on the oncological outcomes afforded by conservative management. We retrospectively investigated the oncological outcomes after SU and RNU in a large multi‐institutional database. Overall, 52 patients were treated with SU and 416 with RNU. There was no statistical difference between the RNU and SU groups for the 5‐year probability of cancer‐specific survival, recurrence‐free survival and metastasis‐free survival. The type of surgery was not a significant prognostic factor in univariate analysis. The results were the same in a subgroup analysis of only unifocal tumours of the distal ureter with a diameter of <2 cm and of low stage (≤T2). Our results suggest that oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases.

OBJECTIVE

• ? To compare recurrence‐free survival (RFS), metastasis‐free survival (MFS) and cancer‐specific survival (CSS) after segmental ureterectomy (SU) vs radical nephroureterectomy (RNU) for urothelial carcinoma (UC) of the upper urinary tract (UUT‐UC) located in the ureter.

PATIENTS AND METHODS

• ? We performed a multi‐institutional retrospective review of patients with UUT‐UC who had undergone RNU or SU between 1995 and 2010.
• ? Type of surgery, Tumour‐Node‐Metastasis status, tumour grade, lymphovascular invasion and positive surgical margin were tested as prognostic factors for survival.

RESULTS

• ? In all, 52 patients were treated with SU and 416 with RNU. The median (range) follow‐up was 26 (10–48) months.
• ? The 5‐year probability of CSS, RFS and MFS for SU and RNU were 87.9% and 86.3%, respectively (P= 0.99); 37% and 47.9%, respectively (P= 0.48); 81.9% and 85.4%, respectively (P= 0.51).
• ? In univariable analysis, type of surgery (SU vs RNU) failed to affect CSS, RFS and MFS (P= 0.94, 0.42 and 0.53, respectively).
• ? In multivariable analyses, pT stage and pN stage achieved independent predictor status for CSS (P= 0.005 and 0.007, respectively); the positive surgical margin and pT stage were independent prognostic factors of RFS and MFS (P= 0.001, 0.04, 0.009 and 0.001, respectively).
• ? The main limitation of the study is its retrospective design, which is due to the rarity of the disease.

CONCLUSIONS

• ? Short‐term oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases and should be considered an option.
• ? In every other case, RNU still represents the ‘gold standard’ for the treatment of UUT‐UC.

     

Randomized trial and local biological effect of autologous platelets used as adjuvant therapy for chronic venous leg ulcers

OBJECTIVES: Platelet products have been proposed as adjuvant therapy for wound healing. We undertook this study to determine the healing effect of topically applied frozen autologous platelets (FAP) on chronic venous ulcers, compared with effect of placebo, and whether use of topical FAP modifies local expression of vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), interleukin 8 (IL-8), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in wound fluid. METHODS: This randomized, placebo-controlled, double-blind trial was carried out in institutional practice, with ambulatory patients with proved chronic venous leg ulcers. In all patients, whole venous blood was drawn for preparation of FAP. FAP or normal saline solution was applied three times per week for up to 12 weeks, together with hydrocolloids and standardized compression bandages. Leg ulcer surface was assessed with numerical pictures. IL-8, VEGF, KGF, and TIMP-1 levels were determined (enzyme-linked immunosorbent assay) in wound fluid after each 4 weeks of treatment. RESULTS: Fifteen patients were randomized into two groups with comparable leg ulcer characteristics. Mean percent reduction in ulcer area was 26.2% in the FAP group versus 15.2% in the placebo group (P =.94). One ulcer in each group was completely healed at study end. Levels of TIMP-1 increased significantly during FAP treatment. IL-8 concentration was significantly lower in wound fluid of healing ulcers than in the fluid of nonhealing ulcers, in both FAP and placebo groups. Growth factor levels were not modified with FAP treatment. CONCLUSION: Topical autologous platelets have no significant adjuvant effect on healing of chronic venous leg ulcers and increased wound fluid TIMP-1 concentration. Ulcer healing is associated with a decrease in wound fluid IL-8.     

The effect of ofloxacin on bacillus calmette-guerin induced toxicity in patients with superficial bladder cancer: results of a randomized, prospective, double-blind, placebo controlled, multicenter study

PURPOSE: We determined whether prophylaxis with ofloxacin could decrease the toxicity of bacillus Calmette-Guerin for transitional cell carcinoma of the bladder. We also investigated the impact of ofloxacin on bacillus Calmette-Guerin antitumor efficacy. MATERIALS AND METHODS: In this randomized, double-blind, multicenter study 115 patients with primary or recurrent superficial bladder cancer (Ta/T1, CIS, G1-G3) and no prior bacillus Calmette-Guerin treatment were randomized to induction treatment with intravesical bacillus Calmette-Guerin (6 plus 3 instillations) plus 200 mg ofloxacin in group 1 or plus placebo in group 2. Adverse events were assessed using a detailed grid of classification for bacillus Calmette-Guerin related adverse events. Mean patient age +/- SD was 65.6 +/- 10.4 years in the 57 group 1 patients and 65.7 +/- 8.7 years in the 58 in group 2. Median followup was 369 and 374 days in groups 1 and 2, respectively. RESULTS: Ofloxacin significantly decreased by 18.5% the incidence of class II or higher moderate and severe adverse events between instillations 4 and 6. The percent of class III adverse events was significantly decreased by ofloxacin between instillations 1 and 9. Although ofloxacin decreased adverse events involving the lower urinary tract, it did not prevent class I adverse events. Compliance with full bacillus Calmette-Guerin treatment was also improved. Of patients in group 1, 80.7% received 9 instillations compared with 65.5% in group 2 (p = 0.092). At 12 months recurrence and progression rates in group 1 and 2 were 12.7% and 17.2%, and 5.5% and 1.7%, respectively. CONCLUSIONS: Prophylactic ofloxacin decreased the incidence of moderate to severe adverse events associated with bacillus Calmette-Guerin intravesical therapy, particularly class III events, which are primarily associated with patient dropout. Compliance with induction and maintenance therapy may be improved by adjuvant ofloxacin therapy. However, long-term comparative studies with other preventive strategies must be done to confirm these initial findings with compliance and recurrence-free survival as the primary end points.     

Association of bone activity, calcium load, aortic stiffness, and calcifications in ESRD

An inverse relationship between arterial calcifications and bone activity has been documented in patients with ESRD. Calcium overload is associated with arterial calcification, which is associated with arterial stiffening. Whether bone activity interacts with calcium load, aortic stiffness, or arterial calcification is unknown. This study assessed the impact of bone activity on the relationships between the dosage of calcium-containing phosphate binders and aortic stiffness (measured by pulse wave velocity) or abdominal aorta calcification score. Aortic stiffness and calcification were both positively associated with calcium load and negatively associated with bone activity. A significant interaction was found between dosage of calcium-containing phosphate binders and bone activity such that calcium load had a significantly greater influence on aortic calcifications and stiffening in the presence of adynamic bone disease. Independent of any other factor, including dosage of calcium-containing phosphate binders, adynamic bone was associated with greater aortic stiffening, suggesting cross-talk between the bone and arterial walls.     

Direct optimization of dynamic systems described by differential‐algebraic equations

This paper presents a method for the optimization of dynamic systems described by index‐1 differential‐algebraic equations (DAE). The class of problems addressed include optimal control problems and parameter identification problems. Here, the controls are parameterized using piecewise constant inputs on a grid in the time interval of interest. In addition, the DAE are approximated using a Rosenbrock–Wanner (ROW) method. In this way the infinite‐dimensional optimal control problem is transformed into a finite‐dimensional nonlinear programming problem (NLP). The NLP is solved using a sequential quadratic programming (QP) technique that minimizes the L_∞ exact penalty function, using only strictly convex QP subproblems. This paper shows that the ROW method discretization of the DAE leads to (i) a relatively small NLP problem and (ii) an efficient technique for evaluating the function, constraints and gradients associated with the NLP problem. This paper also investigates a state mesh refinement technique that ensures a sufficiently accurate representation of the optimal state trajectory. Two nontrivial examples are used to illustrate the effectiveness of the proposed method. Copyright © 2008 John Wiley & Sons, Ltd.     

Case Report—Complex Management of a Postoperative Bronchogastric Fistula After Laparoscopic Sleeve Gastrectomy

Laparoscopic sleeve gastrectomy (LSG) is a new restrictive bariatric procedure increasingly indicated in the treatment of morbid obesity. Postoperative complications are mainly represented by gastric fistula with an occurrence rate of 0% to 5.1% in the literature. This complication is difficult to manage and requires multiple radiological, endoscopic, and surgical procedures. We report herein the case of a 23-year-old woman who underwent LSG for morbid obesity. This patient was reoperated for peritonitis due to a gastric fistula located on the top of the staple line. Five months later, she complained of a cough with fever and expectoration. A methylene blue test and a computed tomography scan diagnosed a postoperative bronchogastric fistula. After failure of aggressive conservative management, radical surgery was performed with total gastrectomy, reconstruction of the diaphragm using the extended latissimus dorsi flap, and a pulmonary lobectomy. This case report highlights the possible issue of the complex management of gastric fistula after LSG.     

Long-term clinical outcome of mitral valve repair in asymptomatic severe mitral regurgitation

Objective: To assess the long-term survival, the incidence of cardiac complications and the factors that predict outcome in asymptomatic patients with severe degenerative mitral regurgitation (MR) undergoing mitral valve repair. Methods: Up to 143 asymptomatic patients (mean age 63 ± 12 years) with severe degenerative MR who underwent mitral valve repair between 1990 and 2001 were subsequently followed up for a median of 8 years. The study population was subdivided into three subgroups: patients with left ventricular (LV) dysfunction and/or dilatation (n = 18), patients with atrial fibrillation and/or pulmonary hypertension (n = 44) and patients without MR-related complications (n = 81). Results: For the patients, 10-year overall and cardiovascular survival was 82 ± 4% and 90 ± 3%. At 10 years, patients without preoperative MR-related complications had significantly better overall survival than patients with preoperative LV dysfunction and/or dilatation (89 ± 4% vs 57 ± 13%, log rank p = 0.001). Patients without preoperative MR-related complications also tended to have a better 10-year overall and cardiovascular survival than patients with atrial fibrillation and/or pulmonary hypertension (overall survival of 79 ± 8%), although this did not reach statistical significance (log rank p = 0.17). Cox regression analysis identified the baseline left ventricular ejection fraction and age as the sole independent predictors of outcome. Conclusion: Our data indicate that in asymptomatic patients with severe degenerative MR, mitral valve repair is associated with an excellent long-term prognosis. Nonetheless, the presence of preoperative MR-related complications, in particular LV dysfunction and/or dilatation, greatly attenuates the benefits of surgery. This suggests that mitral valve repair should be performed early, before any MR-related complications ensue.     

Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism

We investigated the presence of autoantibodies (aAbs) directed against the parathyroid gland in 17 patients with spontaneous isolated acquired hypoparathyroidism. Fourteen patients with acquired hypoparathyroidism (AH) associated with type I or II autoimmune polyendocrinopathy syndrome were also tested in comparison with a control group of 68 subjects without AH, including patients with other autoimmune diseases and healthy blood donors. aAbs against parathyroid tissue were screened using an indirect immunofluorescence technique on primate parathyroid tissue and human parathyroid adenoma. aAbs against the calcium-sensing receptor (CaSR) were analyzed using an immunoblotting assay with the recombinant extracellular domain of the human CaSR as antigen. Seven of the 31 patients with AH were positive for CaSR aAbs. Five of the positive sera were obtained from the group with isolated AH. The two other positive sera were from patients with autoimmune polyendocrinopathy syndrome. The sensitivity of the immunoblotting technique was higher than that of both the radioimmunological test using the extracellular domain of the CaSR and the indirect immunofluorescence technique. There were no positive sera in the control group. In conclusion, using an immunoblotting assay, we demonstrate the presence of CaSR aAbs in about one third of the patients with isolated AH, pointing out the value of detecting such aAbs to assess the autoimmune origin of the disease.     

Nivolumab as adjuvant treatment for a spinal melanocytoma: A case report

Rationale:Meningeal melanocytoma is a rare benign melanocytic tumor of the central nervous system. We report for the first time a case of meningeal melanocytoma treated with immunotherapy.Patient concerns:A 70-year-old man with no medical history was admitted to the Emergency Room. He suffered from a motor and sensory deficit in his left lower limb and a bilateral upper arm neuralgia.Diagnoses:A contrast-enhanced magnetic resonance imaging (MRI) was performed. It showed a C7-T1 bleeding intramedullary tumor. Laminectomy was decided and performed. The results of the pathologic examination showed a melanocytic tumor harboring GNAQ mutation. Meningeal melanocytoma was the final diagnosis.Interventions:The patient was treated with 10 radiotherapy sessions and 6 cycles of nivolumab. A year later, the patient experienced neuralgia again with severe pain and an increasing sensory motor deficit. He underwent a second surgery that was incomplete. As the tumor kept growing, he received temozolomide. But the 6th cycle had to be interrupted due to bedsore infection in the hip area.Outcomes:Disease progression finally led to the patient''s death 3 years after diagnosis.Lessons:This case report is the first about a patient with meningeal melanocytoma treated with immunotherapy. Treatment based on biomolecular mutations will probably change spinal melanocytoma therapeutic approach in the next few years.