scholarly journals Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients

2021 ◽  
pp. ASN.2021050715
Author(s):  
Yu Ho Lee ◽  
Yuki Sato ◽  
Mitsuru Saito ◽  
Shingo Fukuma ◽  
Masaya Saito ◽  
...  

Background: Tertiary lymphoid tissues (TLTs) are ectopic lymphoid tissues found in chronically inflamed organs. Although studies have documented TLT formation in transplanted kidneys, the clinical relevance of these TLTs remains controversial. We examined the impacts of TLTs on future graft function using our histological TLT maturity stages and the association between TLTs and Banff pathologic scores. We also analyzed the risk factors for the development of TLTs Methods: Serial protocol biopsy samples (0-hour, 1-, 6-, and 12-months) without rejection were retrospectively analyzed from 214 patients who underwent living donor kidney transplantation. TLTs were defined as lymphocyte aggregates with signs of proliferation and their stages were determined by the absence (stage I) or presence (stage II) of follicular dendritic cells. Results: Only 4% of patients exhibited TLTs at the 0-hour biopsy. Prevalence increased to almost 50% at the 1-month biopsy and then slightly further for 12 months. The proportion of advanced stage II TLTs increased gradually, reaching 19% at the 12-month biopsy. Presence of stage II TLTs was associated with higher risk of renal function decline after transplantation compared to patients with no TLT or stage I TLTs. Stage II TLTs were associated with more severe tubulitis and interstitial fibrosis/tubular atrophy at 12 months and predicted poorer graft function independently from the degree of interstitial inflammation. Pre-transplantation rituximab treatment dramatically attenuated the development of stage II TLTs. Conclusions: TLTs are commonly found in clinically stable transplanted kidneys. Advanced stage II TLTs are associated with progressive graft dysfunction, independent of interstitial inflammation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5330-5330 ◽  
Author(s):  
Ritsuro Suzuki ◽  
Dai Chihara ◽  
Naoko Asano ◽  
Ken Ohmachi ◽  
Tomohiro Kinoshita ◽  
...  

Abstract [Background] Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma, characterized by the overexpression of cyclin D1 derived from t(11;14)(q13;q32) and poor prognosis. Most MCLs show nodal presentation, but also accompany extranodal involvement, such as bone marrow, peripheral blood or gastrointestinal tract. As a result, many MCLs present with advanced stage disease. Since only a small portion of patients show limited-stage disease, minimal data exist on treatment of patients diagnosed with limited stage disease. Nevertheless, the treatment strategy of MCL is recommended according to the clinical stage of limited- (stage I or non-bulky II) vs. advanced-stage, as well as other types of lymphoma. [Patients and methods] We recently collected 633 patient data of MCL (Chihara, et al. Ann Oncol 2015). Information of clinical stage was available in 626 patients. The patient data were retrospectively analyzed the by the clinical stage at initial presentation. [Results] The clinical stage was I in 24 patients (4%), II in 33 (5%), III in 70 (11%), and IV in 499 (80%). Only one patient presented with bulky stage II. Detailed demographic information by the clinical stage are listed in Table. Age and sex were not significantly different by clinical stage. Limited stage patients were associated with better performance status (PS), less B symptoms, no extranodal involvement, and lower lactate dehydrogenase (LDH) level and white blood cell (WBC) count. Most patients in any stage were treated with cytotoxic chemotherapy, but more patients in limited stage received radiotherapy. The proportion of high-dose cytarabine (HDCA)-containing regimen over CHOP/CHOP-like was higher in advanced stage patients. Complete and overall response rates were 92% and 96% in stage I, 58% and 94% in stage II, 66% and 86% in stage III, and 52% and 82% in stage IV, respectively (P = 0.02). However, the higher response rate in limited stage patients did not translate into better prognosis. The median survival was 11.0 years in stage I, 13.4 years in stage II, 11.5 years in stage III, and 5.6 years in stage IV (Figure). The prognosis was not significantly different among patients with stage I, II, and III (P = 0.33). [Conclusion] Prognosis of limited-stage MCL was almost similar to that of stage III MCL. Although the present study includes several limitations including a retrospective nature and limited number of patients, prognosis of patients with limited-stage MCL was not satisfactory. The significance of radiotherapy, as well as the optimal choice of chemotherapy, for limited-stage MCL needs re-evaluation. Table Table. Figure Figure. Disclosures Suzuki: Chugai: Honoraria; Kyowa Hakko kirin: Honoraria; Bristol-Myers Squibb: Honoraria. Asano:Jannsen: Honoraria; Chugai: Honoraria. Kinoshita:Ono: Research Funding; Gilead: Research Funding; Zenyaku: Honoraria, Research Funding; Takeda: Research Funding; Chugai: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Solasia: Research Funding; Janssen: Honoraria; Kyowa Kirin: Honoraria. Suzumiya:Chugai: Honoraria, Research Funding; Astellas: Research Funding; Eisai: Honoraria, Research Funding; Takeda: Honoraria; Toyama Chemical: Research Funding; Kyowa Hakko kirin: Research Funding. Ogura:SymBio Pharmaceuticals: Consultancy, Honoraria; Celltrion, Inc.: Consultancy, Honoraria.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15585-e15585
Author(s):  
Megan Preston ◽  
Georgia Anne-Lee McCann ◽  
David M. O'Malley ◽  
Christina Boutsicaris ◽  
Larry J. Copeland ◽  
...  

e15585 Background: Neuroendocrine carcinomas (NEC) of the cervix comprise only 2% of all cervical cancers. As a result, prospective data is limited and treatment guidelines rely on literature from lung NEC. The objective of this study was to examine and report on our experience in the management of this rare, aggressive disease. Methods: This was an IRB-approved, single-institution, retrospective review. Study criteria included patients with cervical NEC diagnosed between 1990-2011. Demographic, treatment and survival data was collected. Progression-free survival (PFS) and overall survival (OS) was defined as the time from date of initial treatment until progression or death respectively, or date of last contact. Results: A total of 24 patients met inclusion criteria. The median age at diagnosis was 43. Median PFS was 13.6 months and median OS was 16.4 months. The majority of patients had advanced-stage disease (61% stage II-IV, 39% stage I). Of the 9 patients with stage I disease, 4 were treated with platinum + etoposide-based neoadjuvant chemotherapy and 5 were treated with initial radical surgery. Seven of the 9 patients had post-operative adjuvant therapy consisting of chemotherapy, chemo-radiation or radiation only. Seven of the 9 patients (78%) were alive at last follow-up. Of the two patients who were deceased, one had metastatic disease found at surgery and the other declined adjuvant therapy and died of recurrence. Patients with stage II-IV disease (n=15) had a median PFS and OS of 11.5 and 12.1 months, respectively. Only 2 had no evidence of disease at last encounter. The remainder died without achieving remission. Patients with metastatic disease had significantly worse survival when compared to those with loco-regional disease with a median OS of 8 vs. 28 months (p = .03), respectively. Conclusions: We report one of the largest single-institution experiences of neuroendocrine cervical cancer. Advanced-stage patients had a poor prognosis regardless of therapy. However, multi-modality therapy in early-stage disease resulted in an excellent prognosis (78% survival) for these rare, highly aggressive tumors. These findings support the goal of curative intent for early-stage disease using multi-modality therapy.


2020 ◽  
Author(s):  
Na Li ◽  
Jinhai Gou ◽  
Lin Li ◽  
Xiu Ming ◽  
Tingwenyi Hu ◽  
...  

Abstract Background This study aimed to evaluate the effect of clinicopathologic and surgical factors on the prognosis and fertility outcomes of patients with borderline ovarian tumour (BOT). Methods We performed a retrospective analysis of BOT patients who underwent surgical procedures in West China Second University Hospital from January 2008 to January 2015. The disease-free survival (DFS) outcomes and potential prognostic factors were evaluated using the Kaplan-Meier method and Cox regression analysis, respectively. Furthermore, fertility outcomes were analysed using Pearson Χ 2 and Fisher’s correlation tests. Results A total of 448 patients were included, with a median age of 37.1 years and a median follow-up time of 113 months; 52 (11.6%) recurrences were observed, with a mean recurrence interval of 80.2 months and four (0.9%) deaths; 118 (26.3%) patients underwent staging surgery and the remaining 330 (73.7%) underwent unstaged surgery. In total, 233 patients undergoing fertility-sparing surgery (FSS) attempted to conceive, and 92 (39.48%) of them achieved pregnancy. No significant differences in fertility outcomes were found between the staging and unstaged surgery groups ( P = 0.691). In univariate analysis, staging surgery was associated with DFS (hazard ratio [HR] = 2.191; P = 0.005), but it was not an independent prognostic factor ( P = 0.600) for DFS on multivariate analysis. Multivariate Cox analysis revealed that advanced FIGO stage (≥stage II), positive ascites\pelvic washings, and laparotomy approach were independent prognostic factors for DFS in patients with BOT, whereas advanced stage (≥stage II), laparotomy approach, cystectomy-related procedures, invasive implants, and bilateral tumours were independent prognostic factors for DFS in patients undergoing FSS. In addition, laparoscopy resulted in better prognosis than laparotomy in patients with early-stage (stage I) tumours and a desire for fertility preservation. Conclusion Patients with BOT fail to benefit from surgical staging in terms of prognosis and fertility outcomes. Laparoscopy is recommended for patients with stage I disease who desire to preserve their fertility. Physicians should pay more attention to the risk of recurrence in patients who want to preserve fertility with advanced stage (≥stage II) disease, invasive implants, and bilateral tumours, and choose FSS carefully.


2021 ◽  
pp. 13-15
Author(s):  
Nidhi Singh ◽  
Hiru Navaney ◽  
Yogesh Goel

Background: Early diagnosis and treatment is important in reducing mortality and morbidity. The aim of the study was to describe clinical characteristic, neuroimaging and neurological outcome of TBM in pediatric age group. Methods: A total of 72 patients were included in the study based on inclusion and exclusion criteria. Detailed history and neurological examination, CSF analysis, EEG and CT scan studies done in all patients. Mean age of patient was 59 months (range 6month- 18 year). The majority of these patients were in stage II and III. Results: Among 72 patients included in the study tuberculous meningitis was common in children under 5 years of age (70%). Out of 72 patients 50 patients (70%) were in advanced stage of disease. Most common symptom were fever (90%), altered sensorium (83%), convulsion (80%), th vomiting (75%).7 nerve palsy was most commonly involved (25%), hemiplegia in 15 patients (21%) and papilledema in (14%). CSF culture was positive in 61 patients (85%) with Pleocytosis, lymphocytosis and elevated CSF protein as dominant ndings. Abnormal chest X ray present in 11 patients (50%) in stage I, 9 patients (38) in stage II, and 6 patients (23%) in stage III of disease.: In our study Leptomeningeal enhancement was present in 17 patients (77.27%) in stage I, 16 patients (66.6%) in stage II, 18 patients (69.2%) in stage III of disease. Hydrocephalus was presents in 14 patients (63.63%) in stage I, 15 patients (62.5%) in stage II, 17 patients (65.38%) in stage III of disease. Survival with neurological decit is more in younger age and advanced stage of disease. Conclusion: TBM is an important cause of mortality and morbidity in pediatric patients especially under 5 years of age in countries where tuberculosis is an endemic disease. In our study we found younger the child and more advanced the stage of disease, higher CSF protein value, the greater was mortality and morbidity.


2020 ◽  
Author(s):  
Na Li ◽  
Jinhai Gou ◽  
Lin Li ◽  
Xiu Ming ◽  
Tingwenyi Hu ◽  
...  

Abstract Background This study aimed to evaluate the effect of clinicopathologic and surgical factors on the prognosis and fertility outcomes of patients with borderline ovarian tumour (BOT). Methods We performed a retrospective analysis of BOT patients who underwent surgical procedures in West China Second University Hospital from January 2008 to January 2015. The disease-free survival (DFS) outcomes and potential prognostic factors were evaluated using the Kaplan-Meier method and Cox regression analysis, respectively. Furthermore, fertility outcomes were analysed using Pearson Χ 2 and Fisher’s correlation tests. Results A total of 448 patients were included, with a median age of 37.1 years and a median follow-up time of 113 months; 52 (11.6%) recurrences were observed, with a mean recurrence interval of 80.2 months and four (0.9%) deaths; 118 (26.3%) patients underwent staging surgery and the remaining 330 (73.7%) underwent unstaged surgery. In total, 233 patients undergoing fertility-sparing surgery (FSS) attempted to conceive, and 92 (39.48%) of them achieved pregnancy. No significant differences in fertility outcomes were found between the staging and unstaged surgery groups ( P = 0.691). In univariate analysis, staging surgery was associated with DFS (hazard ratio [HR] = 2.191; P = 0.005), but it was not an independent prognostic factor ( P = 0.600) for DFS on multivariate analysis. Multivariate Cox analysis revealed that advanced FIGO stage (≥stage II), positive ascites\pelvic washings, and laparotomy approach were independent prognostic factors for DFS in patients with BOT, whereas advanced stage (≥stage II), laparotomy approach, cystectomy-related procedures, invasive implants, and bilateral tumours were independent prognostic factors for DFS in patients undergoing FSS. In addition, laparoscopy resulted in better prognosis than laparotomy in patients with early-stage (stage I) tumours and a desire for fertility preservation. Conclusion Patients with BOT fail to benefit from surgical staging in terms of prognosis and fertility outcomes. Laparoscopy is recommended for patients with stage I disease who desire to preserve their fertility. Physicians should pay more attention to the risk of recurrence in patients who want to preserve fertility with advanced stage (≥stage II) disease, invasive implants, and bilateral tumours, and choose FSS carefully.


2020 ◽  
Author(s):  
Na Li ◽  
Jinhai Gou ◽  
Lin Li ◽  
Xiu Ming ◽  
Ting Wenyi Hu ◽  
...  

Abstract Purpose The study is aimed to evaluate the potential effect of clinicopathologic and surgical factors on the prognosis and fertile outcomes in the patients with borderline ovarian tumors. Patients and Methods We performed a retrospective analysis involving BOT patients who had underwent surgical procedures in West China Second University Hospital from January 2008 to January 2015 . The disease-free survival (DFS) outcomes and potential prognostic factors were evaluated using Kaplan-Meier method and Cox regression analysis, respectively. Furthermore, the fertile outcomes were analyzed using Pearson Χ2 and Fish correlation test. Results A total of 448 patients were included with a median age of 37.1 years and a median follow-up time of 113 months. Forty-two (11.6%) recurrences with the mean recurrence interval 80.2 months and four (0.9%) deaths were observed. One hundred and eighteen (26.3%) patients were underwent staging surgery and the remaining 330 (73.7%) patents underwent unstaged surgery. A total of 233 patients undergoing fertility sparing surgery (FSS) attempted to conceive and 92 (39.48%) of them achieved pregnancy. No statistically significant difference of fertile outcomes were found between staging surgery group or not (P=0.691). In univariate analyse, staging surgery was obviously associated with DFS (HR=2.191 P=0.005), but was not an independent prognostic factor (p=0.600) for DFS on multivariate analysis. The multivariate Cox analysis revealed that advanced FIGO stage (≥stage II), positive ascites\pelvic washings and laparotomy approach were independent prognostic factors for DFS in overall patients, whereas advanced stage (≥stage II), laparotomy approach, cystectomy-included procedure, invasive implants and bilateral tumors were independent prognostic factors for DFS in patients undergoing FSS. In addition, laparoscopy approach had better prognosis than laparotomy in patients of early stage (stage I) with fertility desire. Conclusion Patients with BOT fail to benefit from surgical staging in prognosis and fertile outcomes. Laparoscopy will be recommended to patients of stage I with fertility desire. Patients with fertility desire at advanced stage (≥stage II), invasive implants and bilateral tumors should pay more attention to the risk of recurrence and choose FSS carefully.


1999 ◽  
Vol 10 (8) ◽  
pp. 1801-1805
Author(s):  
PETER NICKERSON ◽  
JOHN JEFFERY ◽  
JAMES GOUGH ◽  
PAUL GRIMM ◽  
RACHEL MCKENNA ◽  
...  

Abstract. This group has reported that treatment of subclinical rejection in the first 3 mo posttransplant with corticosteroids decreases late clinical rejections and improves graft function at 2 yr in renal transplant recipients. The current study was performed to determine whether an increase in baseline immunosuppression would decrease the prevalence of early subclinical rejections, as well as the incidence of early and late clinical rejections. Patients received mycophenolate mofetil (MMF) and Neoral cyclosporin A (CsA) posttransplant (n = 29), of which 17 underwent protocol biopsies at months 1, 2, 3, and 6 (Neoral + MMF Protocol Biopsy [Bx]), while 12 declined protocol biopsies (Neoral + MMF Control). These individuals were compared with 72 historical control patients treated with Sandimmune CsA and Imuran, of which 36 had undergone protocol biopsies at months 1, 2, 3, and 6 (Sandimmune + Azathioprine [AZA] Protocol Bx), and 36 had a protocol biopsy at month 6 (Sandimmune + AZA Control). Baseline immunosuppression with Neoral + MMF decreased the incidence of early clinical rejections (0 to 3 mo) and cumulative corticosteroid exposure, but had no impact on the prevalence of early subclinical rejection. Moreover, to maximally decrease the risk of developing late clinical rejections (months 7 to 12) in Neoral + MMF patients required that protocol biopsies be done and that subclinical rejection be treated. The paradoxical finding of recent clinical trials that a reduction in acute clinical rejection has not improved long-term graft outcome may be explained in part by the failure to control subclinical rejection.


2020 ◽  
Vol 104 (S3) ◽  
pp. S39-S39
Author(s):  
Yu Ho Lee ◽  
Yuki Sato ◽  
Mitsuru Saito ◽  
Shingo Fukuma ◽  
Atsushi Komatsuda ◽  
...  

2020 ◽  
Author(s):  
Na Li ◽  
Jinhai Gou ◽  
Lin Li ◽  
Xiu Ming ◽  
Ting Wenyi Hu ◽  
...  

Abstract Purpose The study is aimed to evaluate the potential effect of clinicopathologic and surgical factors on the prognosis and fertile outcomes in the patients with borderline ovarian tumors. Patients and Methods We performed a retrospective analysis involving BOT patients who had underwent surgical procedures in West China Second University Hospital from January 2008 to January 2015 . The disease-free survival (DFS) outcomes and potential prognostic factors were evaluated using Kaplan-Meier method and Cox regression analysis, respectively. Furthermore, the fertile outcomes were analyzed using Pearson Χ2 and Fish correlation test. Results A total of 448 patients were included with a median age of 37.1 years and a median follow-up time of 113 months. Forty-two (11.6%) recurrences with the mean recurrence interval 80.2 months and four (0.9%) deaths were observed. One hundred and eighteen (26.3%) patients were underwent staging surgery and the remaining 330 (73.7%) patents underwent unstaged surgery. A total of 233 patients undergoing fertility sparing surgery (FSS) attempted to conceive and 92 (39.48%) of them achieved pregnancy. No statistically significant difference of fertile outcomes were found between staging surgery group or not (P=0.691). In univariate analyse, staging surgery was obviously associated with DFS (HR=2.191 P=0.005), but was not an independent prognostic factor (p=0.600) for DFS on multivariate analysis. The multivariate Cox analysis revealed that advanced FIGO stage (≥stage II), positive ascites\pelvic washings and laparotomy approach were independent prognostic factors for DFS in overall patients, whereas advanced stage (≥stage II), laparotomy approach, cystectomy-included procedure, invasive implants and bilateral tumors were independent prognostic factors for DFS in patients undergoing FSS. In addition, laparoscopy approach had better prognosis than laparotomy in patients of early stage (stage I) with fertility desire. Conclusion Patients with BOT fail to benefit from surgical staging in prognosis and fertile outcomes. Laparoscopy will be recommended to patients of stage I with fertility desire. Patients with fertility desire at advanced stage (≥stage II), invasive implants and bilateral tumors should pay more attention to the risk of recurrence and choose FSS carefully.


2020 ◽  
Vol 15 ◽  
Author(s):  
Athira K ◽  
Vrinda C ◽  
Sunil Kumar P V ◽  
Gopakumar G

Background: Breast cancer is the most common cancer in women across the world, with high incidence and mortality rates. Being a heterogeneous disease, gene expression profiling based analysis plays a significant role in understanding breast cancer. Since expression patterns of patients belonging to the same stage of breast cancer vary considerably, an integrated stage-wise analysis involving multiple samples is expected to give more comprehensive results and understanding of breast cancer. Objective: The objective of this study is to detect functionally significant modules from gene co-expression network of cancerous tissues and to extract prognostic genes related to multiple stages of breast cancer. Methods: To achieve this, a multiplex framework is modelled to map the multiple stages of breast cancer, which is followed by a modularity optimization method to identify functional modules from it. These functional modules are found to enrich many Gene Ontology terms significantly that are associated with cancer. Result and Discussion: predictive biomarkers are identified based on differential expression analysis of multiple stages of breast cancer. Conclusion: Our analysis identified 13 stage-I specific genes, 12 stage-II specific genes, and 42 stage-III specific genes that are significantly regulated and could be promising targets of breast cancer therapy. That apart, we could identify 29, 18 and 26 lncRNAs specific to stage I, stage II and stage III respectively.


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