Clinicopathological patterns of bladder carcinoma over 1 year: experience from University Hospital of Nepal

Purpose

To define the clinical and pathological patterns of urinary bladder carcinoma from the University Hospital of Nepal.

Methods

This is a retrospective analytical study. Patients with bladder mass who underwent surgery over 1 year and who had data record were included in the study. Demographic profile, type of surgery, findings on clinical examination, cystoscopy findings, histopathological report, tumor stage, and post-surgery adjuvant therapy were analyzed.

Results

Out of 86 patients who underwent transurethral resection of bladder tumor, 77 patients had biopsy-proven malignant bladder tumor. Urothelial cancer was present in 96.1%. Male were 78.6%. The mean age of diagnosis was 65.5?±?11.8 years. Non-muscle-invasive bladder cancer (NMIBC) was 3.7 times more common than muscle-invasive bladder cancer (MIBC). High-grade tumors (58.6%) were more common than low grade (41.4%). The detrusor muscle was present inthe biopsy specimen of 48 patients (64%). Re-TURBT within 2–6 weeks was considered based on histopathology reports for about half of the patients (45.3%). Upstaging and upgrading of the tumor was present in 5.8 and 5.8% of the patients, respectively. Residual tumor without upstaging and upgrading was present in 23.5%. One patient (1.3%) had Clavien–Dindo grade 1, three (4%) patients had grade 2 and two patients (2.7%) had grade 3b.

Conclusion

In the present study, patients with bladder cancer are younger than reported in other studies. Smokers are strongly predisposed. The histological pattern is similar to the Western and Asian populations. NMIBC and MIBC occur in proportion to that described as in other studies. We had a lower rate of recurrence, upstaging and upgrading. We had a lesser rate of acceptance for radical cystectomy in our patients.

     

Moving beyond HLA: A review of nHLA antibodies in organ transplantation

Given the finite graft life expectancy of HLA identical organ transplants and the recognition of humoral graft injury in the absence of donor directed anti-HLA antibodies, the clinical impact of antibodies against non-HLA (nHLA) antigens in transplant injury is being increasingly recognized. The recognition of the impact of nHLA antigen discrepancies between donor and recipient on transplant outcomes is timely given the advances in rapid and lower cost sequencing methods that can soon provide complete maps of all recipient and donor HLA and nHLA mismatch data. In this review, we present a summary of recent reports evaluating the role of nHLA antibodies and their relevance to the field of organ transplantation.     

A modified minimally invasive technique for intra-articular displaced calcaneal fractures fixed by transverse and axial screws

The management of displaced, intra-articular calcaneal fracture represents a surgical challenge to even an experienced orthopedic surgeon. Plate osteosynthesis using an extended lateral approach is complicated by soft tissue problems, while those treated by closed reduction and percutaneous pinning cannot address all the intra-articular fragments sufficiently. The objective of our study is to evaluate restoration of subtalar joint and long-term functional outcomes in intra-articular displaced calcaneal fractures treated with transverse subcondral screws through a small incision on lateral aspect of calcaneus and percutaneously placed axial screws through the calcaneal tuberosity. Forty-five intra-articular calcaneal fractures were managed with this minimally invasive technique. Calcaneal height, width, length, Bohler’s angle, and Gissane angle were measured preoperatively and last follow-up visit. Functional outcomes were assessed on the basis of American Orthopedic Foot and Ankle Society (AOFAS) ankle/hind foot score. Preoperative calcaneal length, height, width, Bohler’s angle, and Gissane angle were improved from 68.62 ± 2.64 to 72.44 ± 2.63 mm, 39.28 ± 2.72 to 32.37 ± 2.65 mm, 47.04 ± 2.56 to 49.55 ± 2.45 mm, 12.66° ± 2.86° to 26.93° ± 2.57°, 123.91° ± 3.13° to 96.06° ± 3.92°, respectively, after surgery with P value <0.001. There were 21 (46.7%) excellent, 17 (37.8%) good, 4 (8.8%) fair, and 3 (6.7%) poor outcomes based on AOFAS ankle/hindfoot scores. Time to unite the fracture was 11.06 ± 1.82 weeks (range 8–16 weeks), and all fractures were united without major complications. Minimally invasive technique through a small incision on lateral aspect of calcaneus gives a moderately good exposure for anatomical restoration of Sander’s type II and III calcaneal fractures fixed with both transverse and axial screws under fluoroscopic guidance.     

Polyclonal Regulatory T Cell Therapy for Control of Inflammation in Kidney Transplants

Early subclinical inflammation in kidney transplants is associated with later graft fibrosis and dysfunction. Regulatory T cells (Tregs) can reverse established inflammation in animal models. We conducted a pilot safety and feasibility trial of autologous Treg cell therapy in three kidney transplant recipients with subclinical inflammation noted on 6‐month surveillance biopsies. Tregs were purified from peripheral blood and polyclonally expanded ex vivo using medium containing deuterated glucose to label the cells. All patients received a single infusion of ~320 × 10⁶ (319, 321, and 363.8 × 10⁶) expanded Tregs. Persistence of the infused Tregs was tracked. Graft inflammation was monitored with follow‐up biopsies and urinary biomarkers. Nearly 1 × 10⁹ (0.932, 0.956, 1.565 × 10⁹) Tregs were successfully manufactured for each patient. There were no infusion reactions or serious therapy‐related adverse events. The infused cells demonstrated patterns of persistence and stability similar to those observed in non‐immunosuppressed subjects receiving the same dose of Tregs. Isolation and expansion of Tregs is feasible in kidney transplant patients on immunosuppression. Infusion of these cells was safe and well tolerated. Future trials will test the efficacy of polyclonal and donor alloantigen‐reactive Tregs for the treatment of inflammation in kidney transplants.     

A Randomized,Prospective Trial of Rituximab for Acute Rejection in Pediatric Renal Transplantation

We report 1‐year outcomes of a randomized study of Rituximab versus standard‐of‐care immunosuppression (Thymoglobulin and/or pulse steroids) for treatment of biopsy confirmed, acute transplant rejection with B‐cell infiltrates, in 20 consecutive recipients (2–23 years). Graft biopsies, with Banff and CADI scores, CD20 and C4d stains, were performed at rejection and 1 and 6 months later. Peripheral blood CMV, EBV and BK viral loads, graft function, DSA, immunoglobulins, serum humanized antichimeric antibody (HACA) and Rituximab, and lymphocyte counts were monitored until 1 year posttreatment. Rituximab infusions were given with a high index of safety without HACA development and increased infections complications. Rituximab therapy resulted in complete tissue B‐cell depletion and rapid peripheral B‐cell depletion. Peripheral CD19 cells recovered at a mean time of ～12 months. There were some benefits for the recovery of graft function (p = 0.026) and improvement of biopsy rejection scores at both the 1‐ (p = 0.0003) and 6‐month (p < 0.0001) follow‐up biopsies. Reappearance of C4d deposition was not seen on follow‐up biopsies after Rituximab therapy, but was seen in 30% of control patients. There was no change in DSA in either group, independent of rejection resolution. This study reports safety and suggests further investigation of Rituximab as an adjunctive treatment for B‐cell‐mediated graft rejection.     

Response to ciclosporin treatment in Ethiopian and Nepali patients with severe leprosy Type 1 reactions

Leprosy type 1 reactions (T1R) are immune-mediated events with inflammation of peripheral nerves and skin. We report the clinical outcomes of a closely monitored open prospective trial in which eight Nepali and 33 Ethiopian patients with T1Rs were treated with an Indian generic formulation of ciclosporin (Cn; 5-7.5 mg/kg/day) for 12 weeks and followed up for 24 weeks after starting treatment. Outcomes were measured using a clinical severity score. Among the Nepalis, 75-100% improved in all acute clinical parameters; 67-100% patients maintained improvement, except for those with acute sensory nerve impairment among whom 67% relapsed after stopping treatment. The skin lesions of all Ethiopians on 5 mg/kg/day of Cn improved and 50-60% had peripheral nerve function improvement. Most Ethiopians needed a higher dose of Cn to improve nerve impairment and neuritis, and 50-78% of them developed worse clinical severity scores when Cn was stopped. Four Ethiopians and two Nepalis developed elevated serum creatinine levels on 7.5 mg/kg/day Cn, and three (9%) Ethiopians developed treatable hypertension. This suggests that Cn monotherapy is an effective treatment for severe T1R with few adverse effects. A dose of 5 mg/kg/day seems efficacious in Nepalis, but a higher dose may be required in Ethiopian patients.     

Complete Steroid Avoidance Is Effective and Safe in Children With Renal Transplants: A Multicenter Randomized Trial With Three‐Year Follow‐Up

To determine whether steroid avoidance in pediatric kidney transplantation is safe and efficacious, a randomized, multicenter trial was performed in 12 pediatric kidney transplant centers. One hundred thirty children receiving primary kidney transplants were randomized to steroid‐free (SF) or steroid‐based (SB) immunosuppression, with concomitant tacrolimus, mycophenolate and standard dose daclizumab (SB group) or extended dose daclizumab (SF group). Follow‐up was 3 years posttransplant. Standardized height Z‐score change after 3 years follow‐up was –0.99 ± 2.20 in SF versus –0.93 ± 1.11 in SB; p = 0.825. In subgroup analysis, recipients under 5 years of age showed improved linear growth with SF compared to SB treatment (change in standardized height Z‐score at 3 years –0.43 ± 1.15 vs. –1.07 ± 1.14; p = 0.019). There were no differences in the rates of biopsy‐proven acute rejection at 3 years after transplantation (16.7% in SF vs. 17.1% in SB; p = 0.94). Patient survival was 100% in both arms; graft survival was 95% in the SF and 90% in the SB arms (p = 0.30) at 3 years follow‐up. Over the 3 year follow‐up period, the SF group showed lower systolic BP (p = 0.017) and lower cholesterol levels (p = 0.034). In conclusion, complete steroid avoidance is safe and effective in unsensitized children receiving primary kidney transplants.