Orthotopic Ileal Neobladder Reconstruction for Bladder Cancer: Is Adjuvant Chemotherapy Safe?

ABSTRACT Objective: We examined our database of patients undergoing radical cystectomy (RC) with orthotopic neobladder (NB) to determine whether adjuvant chemotherapy in this group is safe. Materials and Methods: We performed a retrospective analysis of patients who underwent radical cystectomy and urinary diversion between 1992 and 2004. Relevant clinical and therapeutic data were entered into a database. High-risk bladder cancer patients who underwent NB were identified. They were stratified into 2 groups, those who received adjuvant chemotherapy and those who did not. The incidence of complications between the 2 groups was analyzed and compared. Results: Over the 12-year period, 136 patients underwent RC and NB construction for bladder cancer. Of these, 83 patients were at high risk for recurrence. Nineteen patients received adjuvant chemotherapy and 64 did not. The complication rate in the adjuvant chemotherapy group was 53% and it was 23% in those who did not receive chemotherapy. There were no perioperative or treatment related death. There were 2 patients with grade 4 toxicity in the adjuvant chemotherapy group. There was a statistical difference between these two groups with regard to the incidence of complications. However, none of these complications was life-threatening, required only conservative treatment and caused no long-term disability. Conclusions: Adjuvant chemotherapy is a safe treatment for patients undergoing RC and NB substitution. Hence, the option of orthotopic NB should not be denied in selected bladder cancer patients with high risk for recurrent disease

NOD2 activation enhances macrophage Fcγ receptor function and may increase the efficacy of antibody therapy

IntroductionTherapeutic antibodies have become a major strategy to treat oncologic diseases. For chronic lymphocytic leukemia, antibodies against CD20 are used to target and elicit cytotoxic responses against malignant B cells. However, efficacy is often compromised due to a suppressive microenvironment that interferes with cellular immune responses. To overcome this suppression, agonists of pattern recognition receptors have been studied which promote direct cytotoxicity or elicit anti-tumoral immune responses. NOD2 is an intracellular pattern recognition receptor that participates in the detection of peptidoglycan, a key component of bacterial cell walls. This detection then mediates the activation of multiple signaling pathways in myeloid cells. Although several NOD2 agonists are being used worldwide, the potential benefit of these agents in the context of antibody therapy has not been explored.MethodsPrimary cells from healthy-donor volunteers (PBMCs, monocytes) or CLL patients (monocytes) were treated with versus without the NOD2 agonist L18-MDP, then antibody-mediated responses were assessed. In vivo, the Eµ-TCL1 mouse model of CLL was used to test the effects of L18-MDP treatment alone and in combination with anti-CD20 antibody.ResultsTreatment of peripheral blood mononuclear cells with L18-MDP led to activation of monocytes from both healthy donors and CLL patients. In addition, there was an upregulation of activating FcγR in monocytes and a subsequent increase in antibody-mediated phagocytosis. This effect required the NF-κB and p38 signaling pathways. Treatment with L18-MDP plus anti-CD20 antibody in the Eµ-TCL model of CLL led to a significant reduction of CLL load, as well as to phenotypic changes in splenic monocytes and macrophages.ConclusionsTaken together, these results suggest that NOD2 agonists help overturn the suppression of myeloid cells, and may improve the efficacy of antibody therapy for CLL

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Adrenocortical carcinoma with tumor thrombus in the right hepatic vein

Adrenocortical carcinoma is an unusual neoplasm with very poor prognosis. Patients present with an abdominal mass often exceeding 5 cm or as a functional tumor. Computed tomography is effective to demonstrate the neoplasm as an inhomogeneous adrenal lesion with irregular margins, and magnetic resonance imaging is helpful to visualize invasion into large vessels as well. Reported herein is a case of large adrenocortical carcinoma with tumor thrombus extending into the right hepatic vein

Orthotopic ileal neobladder reconstruction for bladder cancer: is adjuvant chemotherapy safe?

OBJECTIVE: We examined our database of patients undergoing radical cystectomy (RC) with orthotopic neobladder (NB) to determine whether adjuvant chemotherapy in this group is safe. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent radical cystectomy and urinary diversion between 1992 and 2004. Relevant clinical and therapeutic data were entered into a database. High-risk bladder cancer patients who underwent NB were identified. They were stratified into 2 groups, those who received adjuvant chemotherapy and those who did not. The incidence of complications between the 2 groups was analyzed and compared. RESULTS: Over the 12-year period, 136 patients underwent RC and NB construction for bladder cancer. Of these, 83 patients were at high risk for recurrence. Nineteen patients received adjuvant chemotherapy and 64 did not. The complication rate in the adjuvant chemotherapy group was 53% and it was 23% in those who did not receive chemotherapy. There were no perioperative or treatment related death. There were 2 patients with grade 4 toxicity in the adjuvant chemotherapy group. There was a statistical difference between these two groups with regard to the incidence of complications. However, none of these complications was life-threatening, required only conservative treatment and caused no long-term disability. CONCLUSIONS: Adjuvant chemotherapy is a safe treatment for patients undergoing RC and NB substitution. Hence, the option of orthotopic NB should not be denied in selected bladder cancer patients with high risk for recurrent disease

Is adjuvant chemotherapy for bladder cancer safer in patients with an ileal conduit than a neobladder?

To assess the safety of adjuvant chemotherapy in patients with neobladder reconstruction in comparison to ileal conduit, as radical cystectomy and urinary diversion is an effective curative surgical treatment for muscle-invasive and high-risk superficial bladder cancer, and adjuvant chemotherapy is usually considered for patients with clinical stage > T2 and nodal metastasis. We analysed retrospectively patients who had had a radical cystectomy and urinary diversion between 1992 and 2004. Patients with high-risk disease who had adjuvant chemotherapy were identified and stratified based on the type of urinary diversion (ileal conduit or neobladder). The chemotherapy regimen, complications from the adjuvant chemotherapy and other relevant data were analysed. Overall, 343 patients had radical cystectomy, 40 had adjuvant chemotherapy; 25 had an ileal conduit and 15 had a neobladder. Patient characteristics including age, stage and follow-up were similar. In all, 55% of patients had grade 1 toxicity, 23% grade 2, 18% grade 3, and 13% grade 4. No patients had serious organ toxicity and none died. There were no significant differences in the toxicity among the two groups. Adjuvant chemotherapy appears to be safe in patients with a neobladder and equally safe in patients with an ileal conduit. Hence neobladder reconstruction should not be denied to patients with bladder cancer who are at high risk of recurrence and who might require adjuvant chemotherapy

Challenges in understanding the variability of the cryosphere in the Himalaya and its impact on regional water resources

Authors are grateful to UKIERI and DST for supporting us financially through UKIERI-DST Partnership Development Workshops. RR would like to thank the funding agency Ministry of Earth Science (MoES), Government of India for the project titled Estimating Mass balance of glaciers in the Bhaga Basin, Western Himalaya using GPR and Remote Sensing methods (Grant Ref. No: MoES/PAMC/H&C/107/2018-PC-II dated 27.07.2019).The Himalaya plays a vital role in regulating the freshwater availability for nearly a billion people living in the Indus, Ganga, and Brahmaputra River basins. Due to climate change and constantly evolving human-hydrosphere interactions, including land use/cover changes, groundwater extraction, reservoir or dam construction, water availability has undergone significant change, and is expected to change further in the future. Therefore, understanding the spatiotemporal evolution of the hydrological cycle over the Himalaya and its river basins has been one of the most critical exercises toward ensuring regional water security. However, due to the lack of extensive in-situ measurements, complex hydro-climatic environment, and limited collaborative efforts, large gaps in our understanding exist. Moreover, there are several significant issues with available studies, such as lack of consistent hydro-meteorological datasets, very few attempts at integrating different data types, limited spatiotemporal sampling of hydro-meteorological measurements, lack of open access to in-situ datasets, poorly accounted anthropogenic climate feedbacks, and limited understanding of the hydro-meteorological drivers over the region. These factors result in large uncertainties in our estimates of current and future water availability over the Himalaya, which constraints the development of sustainable water management strategies for its river catchments hampering our preparedness for the current and future changes in hydro-climate. To address these issues, a partnership development workshop entitled “Water sEcurity assessment in rIvers oriGinating from Himalaya (WEIGH),” was conducted between the 07th and 11th September 2020. Based on the intense discussions and deliberations among the participants, the most important and urgent research questions were identified. This white paper synthesizes the current understanding, highlights, and the most significant research gaps and research priorities for studying water availability in the Himalaya.Publisher PDFPeer reviewe

Orthotopic ileal neobladder reconstruction for bladder cancer: is adjuvant chemotherapy safe?

OBJECTIVE: We examined our database of patients undergoing radical cystectomy (RC) with orthotopic neobladder (NB) to determine whether adjuvant chemotherapy in this group is safe. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent radical cystectomy and urinary diversion between 1992 and 2004. Relevant clinical and therapeutic data were entered into a database. High-risk bladder cancer patients who underwent NB were identified. They were stratified into 2 groups, those who received adjuvant chemotherapy and those who did not. The incidence of complications between the 2 groups was analyzed and compared. RESULTS: Over the 12-year period, 136 patients underwent RC and NB construction for bladder cancer. Of these, 83 patients were at high risk for recurrence. Nineteen patients received adjuvant chemotherapy and 64 did not. The complication rate in the adjuvant chemotherapy group was 53% and it was 23% in those who did not receive chemotherapy. There were no perioperative or treatment related death. There were 2 patients with grade 4 toxicity in the adjuvant chemotherapy group. There was a statistical difference between these two groups with regard to the incidence of complications. However, none of these complications was life-threatening, required only conservative treatment and caused no long-term disability. CONCLUSIONS: Adjuvant chemotherapy is a safe treatment for patients undergoing RC and NB substitution. Hence, the option of orthotopic NB should not be denied in selected bladder cancer patients with high risk for recurrent disease