Comparison of the renal cortex and the medulla for antibody mediated rejection.

OBJECTIVES: The presence of the peritubular capillaritis and its extent are important for diagnosis of the antibody-mediated rejection in kidneys. However, it is recommended that peritubular capillaritis should only be scored in the cortex. This study aims to focus on peritubular capillaritis scoring both in the cortex and the medulla to understand the value of the medulla in the diagnosis of antibody-mediated rejection. METHODS: Fifty-one allograft renal biopsy were re-evaluated for peritubular capillaritis, C4d and acute tubular injury, separately for the cortex and the medulla according to the Banff. RESULTS: Seventeen cases (33.3%) had peritubular capillaritis both in the cortex and the medulla and three (5.9%) cases had peritubular capillaritis only in the cortex while five (9.8%) cases had only in the medulla. Eighteen (35%) of the cases had C4d staining both in the cortex and the medulla and 14 (27.5%) cases had C4d positivity only in the cortex and 18 (35.3%) cases only in the medulla. Twenty-three (45%) cases had acute tubular injury both in the cortex and the medulla and 31 (60.7%) cases had acute tubular injury only in the cortex and 23 (45.1%) cases had only in the medulla. The sensitivity, specificity, positive and negative predictive values of medullar peritubular capillaritis predicting cortical peritubular capillaritis were 85.7%, 86.7%, 81.8% and 89.7%, respectively. CONCLUSION: In case of absence of the cortical tissue, medulla can be used as a reference for antibody-mediated rejection considering the morphological features, results of donor-specific antibody and renal function tests.

Core curriculum illustration: colonic intussusception due to pedunculated lipoma.

This is the 48th installment of a series that will highlight one case per publication issue from the bank of cases available online as a part of the American Society of Emergency Radiology (ASER) educational resources. Our goal is to generate more interest in and use of our online materials. To view more cases online, please visit the ASER Core Curriculum and Recommendations for study online at http://www.aseronline.org/curriculum/toc.htm .

Mesangial C4d deposition is independently associated with poor renal survival in patients with primary focal segmental glomerulosclerosis.

BACKGROUND: C4d deposition is defined as the footprint of immune injury and it is associated with unfavorable renal outcomes in patients with IgA nephropathy. We searched whether mesangial C4d deposition is associated with poor renal survival in patients with primary focal segmental glomerulosclerosis (FSGS). METHODS: Biopsy specimens were stained with anti-C4d antibody. Patients were classified based on mesangial C4d deposition as C4d-negative and C4d-positive. Groups were compared according to baseline and follow-up clinical variables. Factors that predict renal progression and treatment failure were determined using Cox-regression and multivariate logistic regression models, respectively. RESULTS: Forty-one FSGS patients were followed for a mean of 67.7 ± 40.8 months. C4d-positive group included 18 patients while remaining 23 patients were C4d-negative. Urinary protein excretion and serum creatinine levels at baseline were comparable between groups. Fifteen patients reached the composite primary endpoint which included serum creatinine increasing > 30% from the baseline and reaching > 1.5 mg/dl, and/or evolution to end-stage renal disease (36.6%). In multivariate regression analysis, baseline eGFR (OR 0.71, 95% CI 0.53-0.94; p = 0.016) and mesangial C4d deposition (OR 10.5, 95% CI 1.51-73.18; p = 0.018) were independently associated with treatment failure rates. Mesangial C4d deposition was independently associated with the progression to the primary endpoint (HR 6.54, 95% CI 1.49-28.7, p = 0.013). CONCLUSION: We showed for the first time that mesangial C4d deposition is an independent predictor of disease progression and treatment failure in patients with primary FSGS.

Clinical significance of mesangial IgM deposition in patients with IgA nephropathy.

BACKGROUND: Glomerular immunoglobulin G deposition in patients with immunoglobulin A nephropathy (IgAN) has been shown to be associated with adverse renal outcomes. Clinical significance of mesangial immunoglobulin M (IgM) deposition in these patients remains to be proven. METHODS: One hundred patients who had a diagnosis of IgAN between 2001 and 2017 were enrolled. Patients were divided into two groups based on mesangial IgM deposition status. Groups were compared for demographic, clinical, and pathologic variables at baseline and in follow-up. Cox regression analysis was performed to evaluate the effect of mesangial IgM positivity on renal survival. RESULTS: IgM-positive group included 51% of participants. Baseline demographic and clinical parameters were not significantly different between groups. Mesangial IgM deposition was significantly associated with a higher segmental sclerosis score (p = 0.008). At last visit, median serum creatinine was higher (p = 0.021) and eGFR was lower (p = 0.006) in IgM-positive group. Nineteen (19%) of all patients reached the combined primary outcome which includes doubling in serum creatinine or evolution to ESRD. Cumulative renal survival was lower (p = 0.001) and resistant disease was more frequent in IgM-positive group (p = 0.026). Renal survival at 15 years was 94.2% and 59.7% in IgM-negative and IgM-positive groups, respectively (p = 0.006). Time-averaged proteinuria (HR 2.9; 95% CI 1.9-4.5; p < 0.001) and mesangial IgM deposition (HR, 13.2; 95% CI 1.9-93.1; p = 0.01) were found to be independent predictors of unfavorable renal outcomes. CONCLUSIONS: In conclusion, we demonstrated that mesangial IgM deposition independently associated with worse renal outcomes in patients with IgA nephropathy.

Predictors and histopathological characteristics of non-diabetic renal disorders in diabetes: a look from the tubulointerstitial point of view.

BACKGROUND: Prevalence and characteristics of non-diabetic renal diseases (NDRD) in patients with type 2 diabetes mellitus is different between populations, and seems to be largely dependent on biopsy policies. AIM: To investigate clinical clues for NDRD in patients with type 2 diabetes mellitus and to analyse renal prognosis of patients based on pathological diagnosis. METHODS: We retrospectively searched medical records of 115 patients with type 2 diabetes who underwent a renal biopsy between 2004 and 2018. Patients were divided into three groups as diabetic nephropathy (DN), NDRD + DN or NDRD based on histopathological examination. RESULTS: Thirty-six (31.3%) patients had DN, 33 (28.7%) had DN + NDRD and 46 (40%) had NDRD. The absence of diabetic retinopathy, recent onset of diabetes, abnormal disease chronology, and blood haemoglobin was associated with the presence of NDRD in univariate analysis. Abnormal disease chronology which was defined as the presence of acute proteinuria and/or acute kidney injury that are unexpected to be related to evolution of diabetic nepropathy (odds ratio 4.65, 95% confidence interval 1.44-15.00; P = 0.010) and absence of diabetic retinopathy (odds ratio 3.44, 95% confidence interval 1.32-8.98; P = 0.012) were independently associated with the presence of NDRD in multivariate analysis. Focal segmental glomerulosclerosis was the most frequent type of NDRD. Diseases that affect tubulointerstitial area were more prevalent in the DN + NDRD group compared to the NDRD group (P = 0.001). Renal survival, which was defined as evolution to end-stage renal disease, was 59.5 ± 14.4 months, 93.7 ± 11.7 months and 87.2 ± 2.6 months for DN, DN + NDRD and NDRD groups, respectively (P = 0.005). CONCLUSIONS: Renal biopsy is essential in certain clinical conditions as diagnosis of NDRD is vital for favourable renal survival. DN may facilitate superimposed tubular injury in the presence of toxic insults.

Infliximab-associated focal segmental glomerulosclerosis in a patient with ankylosing spondylitis.

The introduction of tumor necrosis factor-alpha (TNF-α)-targeting drugs has given new opportunities in the treatment of various inflammatory rheumatic diseases and has been the most important development in the treatment of spondyloarthritis (SpA). However, the increasing use and longer follow-up periods of treatment also pose risks of developing various adverse effects ranging from common ones including infections to uncommon renal complications. This report describes a case of infliximab-induced focal segmental glomerulosclerosis (FSGS) in a 40-year-old female patient with ankylosing spondylitis (AS) who presented with asymptomatic proteinuria and microscopic hematuria. To the best of our knowledge, this is the second reported case of FSGS attributed to infliximab (IFX). A review of the English literature was conducted for cases of possible IFX-associated renal disorders in patients with SpA and SpA spectrum diseases. In this respect, the reported renal pathologies were IgA nephropathy, crescentic glomerulonephritis, acute renal artery occlusion, acute tubulointerstitial nephritis (ATIN), FSGS, and membranous glomerulopathy. Furthermore, partial or complete resolution was reported after cessation of therapy. In conclusion, although renal complications of TNF inhibitors (TNFi) are uncommon, spot urine evaluation may be recommended in the follow-up of patients treated with TNFi.

Contribution of Electron Microscopy to the Clinicopathologic Diagnosis in Childhood Glomerular Renal Diseases.

Background: Electron microscopy (EM) provides another diagnostic assessment of glomerular lesions in addition to light and fluorescent microscopy. Objectives: We evaluated the contribution of diagnostic EM in childhood glomerular diseases. Patients and methods: Forty-eight renal biopsies which were assessed by EM between 2000 and 2014 were evaluated. Results: There were 21 (44%) females and 27 (56%) males, ages ranged between 6 and 204 months. EM findings were compatible with light and immunofluorescence microscopy in 65%, made additional contributions to diagnosis in 31% (especially in focal segmental glomerulosclerosis, Alport disease, membranoproliferative glomerulonephritis, dense deposit disease, thin basement membrane disease, and nephronophthisis), and was non-contributory in 4%. Conclusion: Electron microscopic evaluation supports other histopathological diagnoses in most cases, contributes additional diagnostic information in pediatric glomerular disease, especially in FSGS, thin glomerular basement membrane nephropathy, Alport disease, MPGN, and dense deposit disease, and its utilization should clinically justify the increase in cost and testing time.

Treatment of intraoperatively detected peritoneal carcinomatosis of colorectal origin with cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND: Diagnosis of peritoneal carcinomatosis (PC) may be missed by preoperative imaging. We are presenting our experience with incidentally detected PC of colorectal origin treated with cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) at the same operation. METHODS: Between January 2010 and September 2016, 19 patients underwent CRS and IPC due to incidentally detected PC of colorectal origin. Data were analyzed from a prospectively collected database. RESULTS: The median age was 59 (29-78). In three patients, PC was diagnosed during emergency surgery. The primary tumor was located in the rectum (three patients; one with recurrent disease), left colon (9 patients), and right colon (7 patients). All patients underwent CRS and IPC, and one patient operated laparoscopically. Median peritoneal cancer index (PCI) was 5 (range, 3-14), and complete cytoreduction (CC-0) was achieved in 14 patients. After CRS, 8 patients received early postoperative intraperitoneal chemotherapy (EPIC), 7 patients received hyperthermic intraperitoneal chemotherapy (HIPEC), and 4 patients received both HIPEC and EPIC. The median hospital stay was 9 (6-29) days. Postoperative complications occurred in 6 patients. There was no postoperative mortality. Median follow-up was 40.2 (12-94) months. Five-year overall survival was 63.2%. Estimated mean survival time is longer in patients who underwent complete cytoreduction compared to patients having CC-1 or CC-2 cytoreduction (87.7 vs. 20.3 months; p < 0.001). CONCLUSION: Cytoreductive surgery and IPC can be performed safely in patients with intraoperatively detected incidental PC of colorectal origin.

Pretreatment with paricalcitol attenuates level and expression of matrix metalloproteinases in a rat model of renal ischemia-reperfusion injury
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BACKGROUND: Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI). The inflammatory response that drives IRI involves upregulation of matrix metalloproteinases (MMPs), which results in proteolytic degradation of renal microvascular matrix. Evidence suggests a potential protective role of active vitamin D on ischemic injury by downregulating MMPs. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal IRI model and the potential beneficial effect of paricalcitol on both level and expression of MMPs and tubular injury caused by IRI. MATERIALS AND METHODS: 20 Wistar albino rats were divided into three groups: sham-operated, ischemia-reperfusion, and paricalcitol-pretreated. IRI model was induced by bilateral clamping of renal arteries for 45 minutes followed by 24 hours of reperfusion. The analysis of serum creatinine and levels of MMPs were performed after 24 hours of IRI. The effects of paricalcitol on the quantity and expression of MMP-2 and MMP-9 in renal tubular epithelial cells were investigated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy. RESULTS: Creatinine levels decreased in the paricalcitol group, although this was not proven to be significant. Rats in the paricalcitol group showed significant decrease in both level and expression of MMPs and in tubular injury scores as compared to the IRI group. CONCLUSION: Paricalcitol may attenuate renal tubular injury caused by IRI by decreasing both level and expression of MMPs. Further studies are required to investigate the interplay between activated vitamin D and MMPs in AKI.
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Pretreatment with nebivolol attenuates level and expression of matrix metalloproteinases in a rat model of renal ischaemia-reperfusion injury.

AIM: Matrix metalloproteinases (MMPs) are zinc-containing proteinases that are involved in the degradation of extracellular matrix (ECM) and a number of cell surface proteins in order to maintain tissue homeostasis. They are involved in pathogenesis of several ischaemic organ injuries. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal ischaemia-reperfusion injury (IRI) model and the potential beneficial effect of nebivolol, a ß1 -adrenergic receptor blocker, on both MMP-2 and -9 level and expression and tubular injury caused by IRI. METHODS: Twenty Wistar albino rats were divided into three groups: sham-operated , ischaemia-reperfusion, and nebivolol-pretreated. IRI model was induced by bilateral clamping of renal arteries for 45 min followed by 24 h of reperfusion. The analysis of serum creatinine levels, quantity and expression of MMP-2 and MMP-9 were performed after 24 h of IRI. The effects of nebivolol on level and expression of MMP-2 and MMP-9 levels were investigated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy. RESULTS: Creatinine levels increased significantly in the ischaemia-reperfusion group compared to the sham-operated group. Rats in the nebivolol-pretreated group showed significant decrease in expression and quantity of MMP-2 and MMP-9 during IRI. The pathological examinations demonstrated significantly low level of tubular injury score in nebivolol-pretreated group. CONCLUSION: Nebivolol attenuated IRI by decreasing the expression and level of MMP-2 and MMP-9.

IgA nephropathy: association of C4d with clinical and histopathological findings and possible role of IgM.

BACKGROUND: In patients with IgA nephropathy (IgAN) lectin and alternative pathways of the complement can be activated. Our aim was to analyze the association of glomerular and extraglomerular C4d staining--the representative of lectin pathway-with demographic, clinical and histopathological findings in primary IgAN patients. DESIGN: Seventy-three patients were enrolled and after re-evaluation 37 of them were included in this study. Biopsies were analyzed for staining with anti-C4d primary monoclonal antibody by immunohistochemistry. Patients were classified as positive and negative groups based on their glomerular C4d deposition. Groups were compared for their baseline clinical and histopathological findings. RESULTS: Sixteen (43.2%) of 37 patients were C4d-positive. Glomerular C4d-staining was associated with more severe proteinuria (2906 mg/day vs. 1091 mg/day; p = 0.002), lower GFR (54.87 mL/min vs. 95 mL/min; p = 0.023), higher blood pressure (p = 0.022), more severe endocapillary hypercellularity (p < 0.001) and more severe tubular atrophy (p < 0.01). Mesangial IgM deposition was found to be associated with glomerular C4d staining and nephrotic range proteinuria. CONCLUSIONS: Glomerular C4d deposition was found to be associated with more unfavorable histopathological and clinical findings at the time of diagnosis. Association of mesangial IgM deposition with the activation of lectin pathway is a novel finding. Mesangial IgM deposition in our patients may reflect the genetic heterology of IgAN between diverse populations. However, since these data are about association, a cause-and-effect about IgM and IgAN cannot be proven solely with these findings.

Evaluation of c-kit (CD 117) expression as a prognostic factor in testicular germ cell tumors: an Izmir Oncology Group (IZOG) study.

PURPOSE: Despite the successful use of targeted and molecular therapies in other cancers, little progress has been made in the management of testicular germ cell tumors (TGCTs). c-kit (CD 117) is a good target for cancer treatment and possesses an impressive role in the current oncological practice. We aimed to evaluate c-kit expression in early stage TGCTs as a prognostic factor. METHODS: Patients with TGCTs who were referred to the Medical Oncology Clinic and underwent curative surgical operation were included in our study before starting chemo- therapy. Immunohistochemistry was performed on formalin-fixed and paraffin-embedded three-micrometer thick sections with CD 117 Rabbit Anti c-kit in vitro gene kit. Biochemically, we utilized AFP and ß-HCG Immunlite 2000 device with solid phase chemiluminescent immunometric method, and LDH Roche models with the DP-standardized UV method. AFP 0-15 ng/ml, ß-HCG < 0.1 mlu/ml and LDH 240-480 mg/dl were considered as normal values. RESULTS: Sixty-five patients were included in our study. Forty-one (63%) patients had non-seminoma tumors (NSGCTs) and 24 (37%) had seminoma. Statistically significant c-kit expression was found in patients with seminoma (p<0.0001). There was no difference between negative or positive c-kit expression in terms of clinicopathological characteristics, including preoperative serum levels of AFP, ß-HCG, LDH, lymph node involvement, distant metastasis, and IGCCCG risk classification. No correlation was found between these parameters and 5-year progression free survival (PFS) rate except for tumor stage, presence of lymph node metastasis and IGCCCG score (p=0.001, p=0.04, and p=0.0001, respectively). Five-year PFS rate of patients with positive CD 117 was 72.2% (95% CI, 54.6-89.8), and 56.6% (95% CI, 31.2-82.1) for those without CD 117 expression involvement (p=0.12). CONCLUSION: So far, there has been no significant breakthrough in the treatment of cisplatin-refractory TGCTs in the era of targeted therapies. No prognostic importance of c-kit expression has been found in our study. However, we believe that c-kit expression, in numerical terms, can be considered as a good prognostic factor for patients with TGCTs. The fact that all seminoma cases displayed positive c-kit expression is what we think has driven this result.

The prognostic value of detecting symptomatic or asymptomatic recurrence in patients with gastric cancer after a curative gastrectomy.

BACKGROUND: Although studies have investigated whether a routine follow-up should be performed after a gastrectomy, no consensus has been reached on the significance of the follow-up or the optimal surveillance protocol. In the present study, we evaluated the significance of the presence or absence of symptoms in the detection of recurrences after curative gastrectomy for gastric cancer. METHODS: We retrospectively analyzed 173 patients with recurrent gastric cancer who underwent radical gastrectomy. We evaluated the prognostic significance of the presence of cancer-related symptoms at the diagnosis of recurrence, and the relationship between the presence of symptoms and other clinicopathological factors. RESULTS: We detected a symptomatic recurrence in 42.2% of patients. The presence of symptoms were significantly correlated with tumor size, pT stage, pN stage, pathologic stage, and short disease-free interval (<12 mo). The median disease-free survival (DFS), post-recurrence survival (PRS), and overall survival (OS) times for patients with asymptomatic recurrence were significantly longer than those of patients with symptomatic recurrence (disease-free survival was corrected as DFS, 11.1 versus 9.3 mo, P < 0.001; PRS, 4.9 versus 3.1 mo, P = 0.02; OS, 18.3 versus 12.3 mo, P = 0.001, respectively). Multivariate analysis showed that the presence of cancer-related symptoms (P = 0.033; hazard ratio [HR], 0.81) was an independent prognostic factor for PRS, as were short disease-free intervals (P < 0.001; HR, 2.42), age (P = 0.02; HR, 1.53), and the presence of chemotherapy in recurrence (P = 0.001; HR, 0.49). In addition, multivariate analysis indicated that the presence of symptoms, short disease-free interval, and age were also independent prognostic indicators for OS. CONCLUSIONS: Our results demonstrate that symptomatic recurrence is an important prognostic factor for PRS of patients with gastric cancer after a curative gastrectomy. The presence of symptomatic recurrence may be a new and beneficial prognostic marker to evaluate biologic aggressiveness, which is an important determinant of survival at the time of recurrence diagnosis during a follow-up for gastric cancer.

Plexiform fibrohistiocytic tumor of bone.

Plexiform fibrohistiocytic tumor is an extremely rare soft tissue tumor with a low malignancy potential. The patient is usually a child or a young adolescent and the tumor is usually localized in the upper extremities. We report on a case of a 21-year old male with a plexiform fibrohistiocytic tumor in the left fibula admitted to our hospital due to a swelling and pain in the left lower extremity. Radiologically a lytic lesion in the distal end of left fibula consistent with a non-aggressive lesion with low biological activity was found. Treated with curettage, the specimen revealed plexiform proliferation of mononuclear histiocyte-like cells, multinucleated osteoclast-like cells, and spindle fibroblast-like cells in variable proportions histopathologically. Immunohistochemical stains were positive for CD68 in scattered fashion in histiocytes and giant cells, and spindle like cells showed positivity for smooth muscle actin. Under electron microscopy, rough endoplasmic reticulum and collagen bundles in the spindle cells suggested fibroblastic differentiation. Also multiple large electron-dense lysosomal granules in histiocytoid cells were found. Multinucleated giant cells exhibited osteoclast-like appearance. All these findings suggested plexiform fibrohistiocytic tumor. Interestingly, the tumor was localized in bone. During the follow up for 27 months after the resection, there was no recurrence or metastasis.

Long-Term Outcomes of Patients With Amyloidosis Following Kidney Transplant.

OBJECTIVES: Reported graft and patient survival rates in amyloidosis after renal transplant differ considerably between studies. MATERIALS AND METHODS: Group 1 included 24 patients who had end-stage renal disease secondary to amyloidosis. Group 2 (the control group) included 24 consecutive patients who had kidney disease secondary to various causes other than amyloidosis. Comparisons between groups were made for kidney and patient survival rates and other complications following kidney transplant. We also compared survival rates of patients in group 1 versus another control group that included patients with amyloidosis who were treated with hemodialysis (group 3; n = 25). RESULTS: Mean follow-up was 109.5 ± 79.8 months. Biopsy-proven acute rejection and graft failure rates were not significantly different between groups. In group 1 versus group 2, the cumulative 10-year and 20-year patient survival rates were 68.2% versus 86.1% and 36.9% versus 60.3%, respectively (P = .041). Survival was not significantly different in group 1 compared with group 2 and group 3, although patients in group 3 had significantly shorter duration of time to death after the start of renal replacement therapy. CONCLUSIONS: Patient survival may be lower in kidney transplant recipients with amyloidosis compared with patients with end-stage renal disease due to other causes. However, graft failure and acute rejection rates seem to be similar.

Diagnostic performance of magnetic resonance imaging in preoperative local staging of rectal cancer after neoadjuvant chemoradiotherapy

PURPOSE: This paper aims to investigate the diagnostic performance of magnetic resonance imaging (MRI) in predicting the pathologic stage of locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT) and the role of MRI in selecting patients with a pathologic complete response (ypCR). METHODS: Restaging MRI (yMRI) examinations of 136 patients with LARC treated with neoadjuvant CRT followed by surgery were retrospectively analyzed by two radiologists. All examinations were performed on a 1.5 Tesla MRI machine with a pelvic phased-array coil. T2-weighted turbo spin-echo images and diffusion-weighted imaging were obtained. Histopathologic reports of the surgical specimens were the reference standard. The accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) of yMRI in predicting the pathologic T-stage (ypT), N-stage, and ypCR were calculated. The inter-observer agreement was evaluated using kappa statistics. RESULTS: The yMRI results showed 67% accuracy, 59% sensitivity, 80% specificity, 81% PPV, and 56% NPV in identifying ypT (ypT0-2 versus ypT3-4). In predicting the nodal status, the yMRI results revealed 63% accuracy, 60% sensitivity, 65% specificity, 47% PPV, and 75% NPV. In predicting ypCR, the yMRI results showed 84% accuracy, 20% sensitivity, 92% specificity, 23% PPV, and 90% NPV. The kappa statistics revealed substantial agreement between the two radiologists. CONCLUSION: Utilization of yMRI showed high specificity and PPV in predicting the tumor stage and high NPV in predicting the nodal stage; in addition, yMRI revealed moderate accuracy in the T and N classifications, mainly due to underestimating the tumor stage and overestimating the nodal status. Finally, yMRI revealed high specificity and NPV but low sensitivity in predicting the complete response.

Peritubular Capillaritis in Native Kidney Biopsies.

OBJECTIVES: To determine the frequency and predictors of peritubular capillaritis (PTCitis) among native kidney biopsies. METHODS: Consecutive native kidney biopsies of 169 patients were reexamined for capturing possible PTCitis according to the Banff Classification. The relation of PTCitis with demographic and clinicopathologic findings was evaluated. Logistic regression analysis was performed to determine predictors of PTCitis. RESULTS: Peritubular capillaritis was captured in 90 (53.3%) patients, with scores of 1, 2, and 3 in 57 (33.7%), 31 (18.3%), and 2 (1.2%) patients, respectively. The highest frequency of PTCitis was observed in pauci-immune glomerulonephritis. In univariate analysis, male sex, the presence of interstitial inflammation, pauci-immune glomerulonephritis, and a higher serum creatinine level were associated with a higher risk of PTCitis, while severe interstitial fibrosis/tubular atrophy was associated with a lower risk. The presence of interstitial inflammation (odds ratio [OR], 5.94 [95% confidence interval (CI), 1.41-25.03]; P = .015), pauci-immune glomerulonephritis (OR, 3.08 [95% CI, 1.01-9.36]; P = .048), and a higher serum creatinine level (per 1 mg/dL) (OR, 1.56 [95% CI, 1.14-2.11]; P = .005) were independent predictors of PTCitis development in a multivariate regression model. CONCLUSIONS: Peritubular capillaritis is common in native biopsies and more likely to be observed in the presence of interstitial inflammation, pauci-immune glomerulonephritis, and a higher serum creatinine level.

Causes of Granulomatous Inflammation in Native and Allograft Kidneys: Case Series from A Single Center and A Review of the Literature.

OBJECTIVE: Granulomatous interstitial nephritis is a rare finding, and etiology differs by geography. We aimed to investigate the distribution of causes of granuloma/granulomata in the kidney and renal survival of these patients in a tertiary care hospital in Western Turkey. MATERIAL AND METHOD: Medical records of adults who underwent a kidney biopsy procedure in our institution between January 2000 and June 2019 were reviewed. Pathology reports were searched for biopsies where a granuloma was identified. RESULTS: Nineteen of 1121 (1.7%) kidney biopsies included granuloma, 17 in native kidneys, and 2 in transplants. The majority of indications for native kidney biopsy was a rise in serum creatinine. Etiologies of granuloma included the following: pauci-immune vasculitis (n=11, 64.7%), tuberculosis (n=2, 11.8%), drug-induced (n=2, 11.8%), tubulointerstitial nephritis/uveitis (TINU) syndrome (n=1, 5.9%), and systemic-lupus erythematosus (n=1, 5.9%). Despite treatment, 6 of 11 (54.5%) patients with vasculitis developed end-stage kidney disease (ESKD) during the median follow-up of 16 months. Both of the patients with tuberculosis, and the patient with TINU syndrome developed ESKD months after the kidney biopsy, despite appropriate therapies. The only case with drug-induced granuloma and both cases with allograft kidney granuloma responded well to glucocorticoids, achieving a complete renal recovery. CONCLUSION: The majority of our series had granuloma in the kidney secondary to vasculitis and renal outcomes appear considerably unfavorable despite treatment, probably related to the primary diagnosis. Multicenter studies are needed to better determine the etiology and outcome of each granuloma etiology at different geographic locations.

Molecular characteristics of colorectal hyperplastic polyp subgroups.

BACKGROUND/AIMS: The importance of hyperplastic polyps during colorectal carcinogenesis is appreciated related to the understanding of serrated pathway. The morphologic subtypes of hyperplastic polyps in carcinogenesis and the nomenculature of lesions with both hyperplastic and adenomatous areas are controversial. We aimed to reveal the molecular properties of hyperplastic polyp subtypes and the molecular changes in polyps containing both hyperplastic and adenomatous areas. Matherial and Methods: 49 hyperplastic polyps [19 microvesicular (MVHP), 19 goblet-rich (GRHP), 11 mucin-poor (MPHP)] and 10 mixed hyperplastic and adenomatous polyps were analysed for KRAS, BRAF mutations and MSI with real-time PCR. RESULTS: 68,4% of MVHPs and 81% of MPHPs which were localized in right colon had BRAF mutations. While none of the GRHPs showing a KRAS mutation with a rate of 73% was localized in the ascending colon, 63% of them were localized in the rectosigmoid area. In five (50%) of the mixed polyps, KRAS mutation was detected both in the hyperplastic and adenoma components. There was no BRAF mutation in any of the mixed polyps. However, in two cases, the hyperplastic component was MSI-H and the adenoma area was MSS. CONCLUSION: Hyperplastic polyps, even if smaller than 5 mm, are precancerous lesions bearing different mutations. GRHPs with predominant KRAS mutations and MVHPs and MPHSs with predominant BRAF mutations are precancerous. Although the molecular investigations for HPP/SP are not necessary the morphological subtyping should be included if the case is diagnosed with HPP/SP as it will be useful for attracting the gastroenterologist's attention.

The Prognostic Implications of FIX and FLO Patterns in Mucinous Colon Carcinomas.

PURPOSE: Colon mucinous carcinomas (MUCs) have two morphological patterns: (i) glands lined by mucinous epithelium with direct contact to the stroma (FIX) and (ii) carcinoma cells floating in mucin (FLO). In this study, we evaluated the prognostic value of these patterns. METHODS: Digital images were captured from the 38 MUC's tissue sections. A grid with 140 points was laid over the computer screen. Totally, 100 points, falling on tumor cells floating in mucin (FLO patterned cells) or on cells contacting stroma (FIX patterned cells), were counted. Tumors were grouped according to the median value of the FIX patterned cells. Cases with more than this value were grouped as FIX and less were grouped as FLO cases. The prognostic value of FIX and FLO pattern was evaluated. RESULTS: The median for FIX patterned cells was 66%, and the cases with lower values than this were grouped as FLO (N = 18; 47.37%), while the rest were grouped as FIX cases. There was no significant difference between FIX and FLO cases for overall survival cases (p = 0.167). For FIX cases, 62.7 and 51.3% of the patients were alive at second and third years, while this was 78.9 and 72.4% for the FLO group, respectively. CONCLUSIONS: This is the first study using a quantitative methodology depending on count pointing to evaluate FIX/FLO feature of MUCs to the best of our knowledge, although we could not observed any prognostic and clinicopathologic relationship statistically. This distinctive feature should be studied in larger cohorts with prognostic information, with a quantitative method, like the one that was applied in this study, in order to achieve strict conclusions.