A clinically applicable six-segmented foot model

We describe a multi‐segmented foot model comprising lower leg, rearfoot, midfoot, lateral forefoot, medial forefoot, and hallux for routine use in a clinical setting. The Ghent Foot Model describes the kinematic patterns of functional units of the foot, especially the midfoot, to investigate patient populations where midfoot deformation or dysfunction is an important feature, for example, rheumatoid arthritis patients. Data were obtained from surface markers by a 6 camera motion capture system at 500 Hz. Ten healthy subjects walked barefoot along a 12 m walkway at self‐selected speed. Joint angles (rearfoot to shank, midfoot to rearfoot, lateral and medial forefoot to midfoot, and hallux to medial forefoot) in the sagittal, frontal, and transverse plane are reported according to anatomically based reference frames. These angles were calculated and reported during the foot rollover phases in stance, detected by synchronized plantar pressure measurements. Repeated measurements of each subject revealed low intra‐subject variability, varying between 0.7° and 2.3° for the minimum values, between 0.5° and 2.1° for the maximum values, and between 0.8° and 5.8° for the ROM. The described movement patterns were repeatable and consistent with biomechanical and clinical knowledge. As such, the Ghent Foot model permits intersegment, in vivo motion measurement of the foot, which is crucial for both clinical and research applications. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:655–661, 2012     

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.

     

Prognostic Value of BRAF V600 Mutations in Melanoma Patients After Resection of Metastatic Lymph Nodes

Purpose

BRAF ^V600 mutations are frequent in melanomas, and BRAF^V600-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ??2?mm according to BRAF ^V600 mutations and other previously reported prognostic criteria.

Methods

This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF ^V600 mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60?% melanoma cells.

Results

BRAF mutations (p.V600E and p.V600K in 83 and 14?% of cases, respectively) were detected in 40?% of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3?%, with a median OS of 1.4 and 2.8?years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P?=?0.005, hazard ratio 2.2, 95?% confidence interval 1.3?C3.9) and BRAF status (P?=?0.005, hazard ratio 1.9, 95?% confidence interval 1.2?C3.1).

Conclusions

BRAF ^V600 status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.     

Predictors of a favourable response to icodextrin in peritoneal dialysis patients with ultrafiltration failure

BACKGROUND AND AIMS: Icodextrin is a starch-derived glucose polymer that causes sustained ultrafiltration in long dwells in peritoneal dialysis. The aim of this study was to assess factors that were predictive of an increment in ultrafiltration following the introduction of icodextrin in patients with refractory fluid overload. METHODS: Thirty-nine patients (20 male/19 female, mean age 57.7 +/- 2.4 years) on peritoneal dialysis were enrolled in a prospective pretest/post-test, open-label study. All patients had symptomatic fluid overload refractory to fluid restriction (<800 mL/day), frusemide doses of 250 mg or more daily, optimization of dwell time and use of hypertonic dextrose. An icodextrin exchange was substituted for a 4.25% dextrose exchange for the long-dwell period. RESULTS: After 1 month, median (interquartile range) 24 h ultrafiltration volume increased by 500 mL (interquartile range: 50-1000). An increase in ultrafiltration volume correlated positively with the dialyate : plasma creatinine ratio at 4 h (r = 0.498, P = 0.001) and negatively with the ratio of dialysate glucose concentrations at 4 and 0 h (r = -0.464, P = 0.003). On multivariate regression analysis, high transporter status was predictive of a greater ultrafiltration response to icodextrin relative to dextrose peritoneal dialysis exchanges. Age, sex, race, peritoneal dialysis duration, peritoneal dialysis modality, diabetes mellitus, baseline albumin, and baseline ultrafiltration volume were not significantly correlated with the change in ultrafiltration volume. CONCLUSION: Icodextrin significantly augments ultrafiltration volumes in patients with refractory fluid overload. A high peritoneal membrane transporter status is the best predictor of a favourable ultrafiltration response to icodextrin.     

Endovascular management of visceral artery aneurysms: When to watch,when to intervene?

Visceral artery aneurysms (VAA) include splanchnic and renal artery aneurysms. They represent a rare clinical entity, although their detection is rising due to an increased use of cross-sectional imaging. Rupture is the most devastating complication, and is associated with a high morbidity and mortality. In addition, increased percutaneous endovascular interventions have raised the incidence of iatrogenic visceral artery pseudoaneurysms (VAPAs). For this reason, elective repair is preferable in the appropriately chosen patient. Controversy still exists regarding their treatment. Over the past decade, there has been steady increase in the utilization of minimally invasive, non-operative interventions, for vascular aneurysmal disease. All VAAs and VAPAs can technically be fixed by endovascular techniques but that does not mean they should. These catheter-based techniques constitute an excellent approach in the elective setting. However, in the emergent setting it may carry a higher morbidity and mortality. The decision for intervention has to take into account the size and the natural history of the lesion, the risk of rupture, which is high during pregnancy, and the relative risk of surgical or radiological intervention. For splanchnic artery aneurysms, we should recognize that we are not, in reality, well informed about their natural history. For most asymptomatic aneurysms, expectant treatment is acceptable. For large, symptomatic or aneurysms with a high risk of rupture, endovascular treatment has become the first-line therapy. Treatment of VAPAs is always mandatory because of the high risk of rupture. We present our point of view on interventional radiology in the splanchnic arteries, focusing on what has been achieved and the remaining challenges.     

Critical influence of natural regulatory CD25+ T cells on the fate of allografts in the absence of immunosuppression

BACKGROUND: Allografts are occasionally accepted in the absence of immunosuppression. Because naturally occurring CD4(+)CD25(+) regulatory T cells (natural CD25(+) Treg cells) have been shown to inhibit allograft rejection, we investigated their influence on the outcome of allografts in nonimmunosuppressed mouse recipients. METHODS: We compared survival times of male CBA/Ca skin grafts in female CBA/Ca recipients expressing a transgenic anti-HY T-cell receptor on a RAG-1(+/+) (A1[M]RAG+) or a RAG-1(-/-) (A1[M]RAG-) background. Depletion of natural CD25(+) Treg cells in A1[M]RAG+ mice was achieved by in vivo administration of the PC61 monoclonal antibody. The influence of natural CD25(+) Treg cells on the fate of major histocompatibility complex class II-mismatched (C57BL/6X bm12)F1 skin or bm12 heart transplants in C57BL/6 recipients was also assessed. Finally, we investigated the impact of natural CD25(+) Treg cells on the production of T-helper (Th)1 and Th2 cytokines in mixed lymphocyte cultures between C57BL/6 CD4(+) CD25(-) T cells as responders and bm12 or (C57BL/6X bm12)F1 antigen-presenting cells as stimulators. RESULTS: Male allografts were spontaneously accepted by female A1(M)RAG+ mice but readily rejected by female A1(M)RAG+ mice depleted of natural CD25(+) Treg cells by pretreatment with the PC61 monoclonal antibody. Depletion of CD25(+) Treg cells also enhanced eosinophil-determined rejection of (C57BL/6X bm12)F1 skin grafts or bm12 cardiac grafts in C57BL/6 recipients. Finally, natural CD25(+) Treg cells inhibited the production of interleukin (IL)-2, interferon-gamma, IL-5, and IL-13 in mixed lymphocyte culture in a dose-dependent manner. CONCLUSION: Natural CD25(+) Treg cells control Th1- and Th2-type allohelper T-cell responses and thereby influence the fate of allografts in nonimmunosuppressed recipients.     

Late relapse of germ cell tumors

Objective  To assess the main characteristics of late relapsing malignant germ cell tumors (MGCTs). These tumors are rare and occur by definition 2 years or later after successful treatment. Methods  We present relevant literature on relapsing MGCT in order to highlight the following issues: incidence, impact of initial treatment on the subsequent risk of late relapse, treatment, and survival. Results  A pooled analysis of 5,880 patients with MGCT revealed late relapses in 119 of 3,704 (3.2%) and in 31 of 2,176 (1.4%) patients with non-seminoma and seminoma, respectively. The retroperitoneal space is the predominant site of relapse in both histological types. The initial treatment is important for the risk and localization of late relapses. Patients with single site teratoma are usually cured by surgery alone, whereas viable MGCT or teratoma with malignant transformation may require multimodal treatment with chemo- and/or radiotherapy as well as surgery. Surgery is the most important part in the treatment of late relapses. Salvage chemotherapy should, if feasible, be based on a representative biopsy. Five-year cancer-specific survival is above 50% in the recent large series and reaches 100% in case of single site teratoma. Conclusions  Treatment of late relapsing MGCT patients is challenging and should be performed in experienced centers only. Referral of late relapsing patients to high-volume institutions ensures the best chances of cure and enables multimodal treatment, and contributes to increased knowledge of tumor biology as well experience with the clinical course of these patients.     

Laparoscopic Sleeve Gastrectomy as Revisional Procedure for Failed Gastric Banding and Vertical Banded Gastroplasty

Background  The problem of revision of failed gastric banding (GB) and vertical banded gastroplasty (VBG) procedures has become a common situation in bariatric surgery. Laparoscopic sleeve gastrectomy (LSG) has been recently used to revise failed restrictive procedures. The objective of this study is to evaluate the results of LSG as revisional procedure for failed GB and VBG. Methods  A prospective held database was questioned regarding patients' demographic, indication for revision, conversion to open surgery, morbidity, percentage of excess weight loss (%EWL), evolution of comorbidities, and need for a second procedure after LSG. Results  Forty-one patients, 34 women and seven men with a mean age of 42 years (range 19 to 63 years) and a mean body mass index at 49.9 kg/m² (range 35.9–63 kg/m²), underwent laparoscopic conversion of GB (36 patients) and VBG (five patients) into LSG. Indication for revisional surgery was insufficient weight loss in all the cases. All procedures were completed laparoscopically. There was no mortality and five patients (12.2%) developed complications (high leak, one patient; intra-abdominal abscess, three patients; and complicated incisional hernia, one patient). At a mean follow-up of 13.4 months, %EWL is on average 42.7% (range 4–76.1%). Six patients had a second procedure (four had laparoscopic duodenal switch, one had laparoscopic Roux-en-Y gastric bypass, and one had laparoscopic biliopancreatic diversion). Conclusion  Conversion of GB and VBG into LSG is feasible and safe. LSG is effective in the short term with a mean %EWL of 42.7% at 13.4 months. Long-term results of LSG as revisional procedure are awaited to establish its efficacy in the long term.