Evaluation of blood supply and metabolism in tumor, axillary lymph node and normal breast tissue with F-18 FDG PET/CT in breast cancer: comparison with pathological prognostic factors.

BACKGROUND AND PURPOSE: Perfusion parameters obtained in F-18 FDG PET/CT performed for staging purposes in breast cancers may provide additional information about tumor biology as well as glucose metabolism. The aim of this study was to evaluate throughout F-18 FDG PET/CT the relationship between blood flow and glucose metabolism and histological parameters of the primary tumor, normal mammary gland, and axillary lymph nodes in breast cancer patients. MATERIALS AND METHODS: Sixty six female patients (mean age 51 y ± 12,81) were prospectively included to this study. We performed dynamic blood flow (f) study that started with 296-444 MBq (8-12 mCi) F-18 FDG injection and lasted for 10 minutes, and glucose metabolism (m) imaging one hour later. On each frame, mean activity concentration (AC) values (Bq/mL) were recorded on a spherical volume of interest (VOI) having a volume of ~ 1 cm3 on the hottest voxel of primary tumor (T), across normal breast gland (NG) and ipsilaterally axillary lymph nodes (iLN). Correlations among PET parameters and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (c-erbB2) and Ki67 index were analyzed. RESULTS: T volume (TV) ranged from 1.1 to 85.28 cm3 [median (IR): 6.44 (11.78)]. There were positive correlations between c-erbB2 and TACf and between c-erbB2 and iLNACf (p = 0.045, r = + 0.248; p = 0.050, r = + 0.242). In the ER positive (ERP) patients, TV and TACm were significantly lower than those of ER negative (ERN) (respectively p = 0.044 and p = 0.041). In patients with two positive Ki-67 indices, iLN-SUVmax was significantly higher than one-positive patients (p = 0.020). There was a negative correlation between NGACm and histological grade of tumor (p = 0.005, r = - 0.365). CONCLUSIONS: Breast cancer shows differences in progression, metastasis and survival due to its diversity in terms of molecular, biological and angiogenesis. High glucose metabolism in breast cancers is associated with tumor aggressiveness. Being able to examine tumor tissue characteristics such as blood flow and glucose metabolism with a single diagnostic technique and to reveal its relationship with histological parameters can provide a reliable pretherapeutic evaluation in breast cancers.

Human chorionic gonadotropin expression in endometrial hyperplasia and endometrial carcinoma: could it be a new marker?

OBJECTIVE: Human chorionic gonadotropin (hCG) is a glycoprotein hormone expressed in a variety of tumors and is correlated with advanced stage disease and poor prognosis. This study aimed to determine hCG expression immunohistochemically in endometrial specimens obtained from patients with normal endometrium, endometrial hyperplasia, and endometrial carcinoma, and to determine if there is a correlation between invasiveness and hCG positivity. METHODS: The histologic materials and medical records for patients diagnosed with normal endometrium, endometrial hyperplasia with/without atypia, and endometrial carcinoma between September 2017 and September 2020 were retrospectively reviewed. Immunohistochemical staining for hCG was performed and analyzed semi-quantitatively. RESULTS: A total of 96 patients were included: normal endometrium (27.1%) (n=26); endometrial hyperplasia without atypia (25%) (n=24); atypical endometrial hyperplasia (22.9%) (n=22); endometrioid endometrial cancer (25%) (n=24). Median age of the patients was 48 (range 28-81) years. hCG was positive in 8.3% of patients with endometrial hyperplasia without atypia, 18.2% in those with atypical endometrial hyperplasia, and 41.7% in those with endometrial cancer (p<0.001). None of the patients with normal endometrium had a positive hCG. The rate of endometrial cancer was 62.5% in the hCG-positive group and 17.5% in the hCG-negative group. CONCLUSION: hCG is expressed to a significantly greater degree in patients with atypical endometrial hyperplasia and endometrial carcinoma and it may be potentially used as a marker for these lesions.

An unusual form of kidney injury without glomerulonephritis in microscopic polyangiitis: a case report.

BACKGROUND: Microscopic polyangiitis (MPA), a kind of antineutrophil cytoplasmic autoantibody associated vasculitis (AAV), predominantly affects small-sized vessels. MPA is a significant cause of the pulmonary-renal syndrome. Pauci-immune necrotizing and crescentic glomerulonephritis is the typical renal histological feature of AAV. Tubulointerstitial lesions may occur and mostly form with inflammatory cell infiltration in the interstitium. However, a few cases reported only tubulointerstitial involvement without glomerular lesions in patients with MPA. CASE PRESENTATION: We present an MPA case, a 70-year-old male patient diagnosed with acute kidney injury accompanying the dialysis requirement. Only acute tubulointerstitial nephritis was revealed in kidney biopsy without evidence of glomerular injury. Also, interstitial pulmonary fibrosis was determined on computerized tomography, and myeloperoxidase antineutrophil cytoplasmic autoantibody was positive. Consequently, we have considered the main diagnosis as MPA. We did not prefer a standard tubulointerstitial nephritis treatment regimen due to the presence of life-threatening systemic vasculitis. Treatment was established like crescentic glomerulonephritis. Induction therapy consisted of pulse steroid, cyclophosphamide, and plasmapheresis. Unfortunately, severe SARS-CoV-2 infection caused death during induction therapy in this case. CONCLUSIONS: The lack of glomerular injury and solely interstitial inflammation is atypical regarding AAV involvement in the kidney. This diversity might be initially considered as only a simple histological elaboration. However, it is a significant entity for guiding the treatment of AAV.

Patient Outcomes of Henoch-Schönlein Purpura Nephritis According to the New Semiquantitative Classification.

Background: A new semiquantitative classification (SQC) for pediatric Henoch-Schönlein nephritis (HSN) was defined recently. The outcomes of pediatric HSN patients are reevaluated according to the new classification. Methods: Primary kidney biopsies from 80 HSN patients were scored using the new SQC. The International Study of Kidney Disease in Children (ISKDC) and SQC classifications were compared in terms of the patient outcomes. Outcomes were defined as: Outcome A (n = 44) patients with no sign of renal disease, Outcome B (n = 32) patients with minor urinary abnormalities, and Outcome C (n = 4) patients with active renal disease. Results: The patients with outcome C had significantly higher biopsy scores and chronicity indices than patients in group A. There was no significant difference in areas under the curve between total biopsy SQC scores and ISKDC findings. Conclusions: Our results suggest that the modified SQC is not more sensitive than ISKDC classification for predicting the outcome in HSN cases.

Twenty children with non-Wilms renal tumors from a reference center in Central Anatolia, Turkey

Background/aim: Non-Wilms renal tumors (NWRTs) are rarely encountered in children. The aim of this study is to determine the treatment strategies, prognosis, outcomes, and survival of children with NWRTs at Erciyes University in Kayseri, Turkey. Materials and methods: Medical records of all patients (n = 20) treated for NWRTs over a 23-year period (1995­2018) were reviewed retrospectively. Results: There was male predominance (female/male: 7/13); the median age at diagnosis was 3.2 years old (0.1­13.5 years old). The major histological groups included mesoblastic nephroma (MBN), (n: 5, 25%), malignant rhabdoid tumor (MRT), (n: 5, 25%), renal cell carcinoma, (n: 3, 15%), inflammatory myofibroblastic tumor (n: 2, 10%), multilocular cystic renal tumors (n: 2, 10%), metanephric adenoma (n: 1, 5%), renal neuroblastoma (n: 1, 5%), and bilateral renal Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) (n: 1, 5%). All of the patients with NWRTs had radical nephrectomy except the child with bilateral renal ES/PNET. Six children died because of progressive disease; the mortality rate was 30% (n: 6). Conclusion: We have made the first report of bilateral renal involvement of ES/PNET in the English medical literature. Physicians dealing with pediatric renal masses should be alert to the high mortality rate in children with MRT, MBN, and ES/PNET and they should design substantial management plans for NWRTs.

Comparison of the Upgrading Rates of International Society of Urological Pathology Grades and Tumor Laterality in Patients Undergoing Standard 12-Core Prostate Biopsy versus Fusion Prostate Biopsy for Prostate Cancer.

BACKGROUND: Histopathological discrepancies between biopsy and radical prostatectomy (RP) specimens may lead to unnecessary, excessive, or incomplete treatment in prostate cancer (PCa) patients. OBJECTIVES: To compare the upgrading rates of International Society of Urological Pathology (ISUP) grades and tumor laterality in patients that underwent standard 12-core transrectal ultrasound-guided standard prostate biopsy (SPB) versus multiparametric magnetic resonance-guided fusion prostate biopsy (FPB) for PCa. METHODS: This retrospective study included 152 patients that underwent prostate biopsy and RP in our clinic. The patients were divided into 2 groups: Group A (n = 90) included patients that underwent SPB and Group B (n = 62) included patients that underwent FPB (targeted biopsy + standard biopsy). Upgrading of ISUP grades, tumor laterality, and upgrading of tumor laterality were compared between the 2 groups. Upgrading of tumor laterality defined as detection of tumor at both lobes in RP pathology while it was at unilateral lobe in biopsy pathology. RESULTS: ISUP grade 1 was the most common histopathology in both groups. The ISUP upgrading rate on final pathology was significantly lower in the FPB group compared to the SPB group (22.7 vs. 37.7%; p < 0.048). Similarly, the upgrading rate of tumor laterality was lower in the FPB group compared to the SPB group (37.7 vs. 9.7%; p < 0.001). CONCLUSION: The results suggested that FPB can provide more accurate results compared to SPB.

Correlation between prenatal ultrasound and fetal autopsy findings on urinary system anomalies terminated in the second trimester.

OBJECTIVE: This prospective study was designed to compare ultrasound and autopsy findings on fetal urinary system malformations in second trimester terminations of pregnancy to evaluate the degree of agreement of such findings. METHODS: From January 2003 to October 2012, a total of 308 second trimester terminations of pregnancy were performed because of fetal malformation diagnosed through second trimester ultrasound examination at a tertiary referral center. RESULT: Among 308 second trimester fetuses with congenital anomalies, 62 (20.1%) had urinary anomalies. Ultrasound and fetal autopsy findings were in full agreement for urinary system malformations in 45 (72.6%) of 62 cases. In six (9.7%), autopsy confirmed the malformations detected by ultrasound but showed additional lesser urinary anomalies. In 10 (16.1%) cases, autopsy revealed major urinary anomalies not determined by ultrasound. In one case (1.6%), ultrasound reported bilateral renal agenesis; however, autopsy revealed a horseshoe kidney. The ultrasound screening sensitivity was 83.8%, and specificity was 99.5%. CONCLUSION: The results showed that prenatal ultrasound achieved a high accuracy in diagnosing fetal urinary malformations. However, fetal autopsy occasionally adds valuable information to prenatal ultrasound findings.

Compare the effects of intravenous and intraperitoneal mesenchymal stem cell transplantation on ultrafiltration failure in a rat model of chronic peritoneal dialysis.

AIM: The purpose of this study was to compare the possible healing effects of intraperitoneal (IP) and intravenous (IV) mesenchymal stem cell (MSC) transplantation on ultrafiltration failure (UFF) in a chronic rat model of peritoneal dialysis (PD). METHODS: Rats were initially divided into two groups. The UFF-group received once-daily IP injections of 20 mL of 3.86% glucose PD solution for six weeks to stimulate the development of UFF, and a control group received no injections. The UFF group was sub-divided into four groups: an UFF-C group, a MSC-IP group, a MSC-IV group and a placebo (P) group. Peritoneal equilibration tests (PETs) and peritoneal biopsies were performed in the control and UFF-C groups. MSCs were administered by IP injection in the MSC-IP group and by IV injection in the MSC-IV group. The P group received IP injection of placebo. PETs and peritoneal biopsies were performed in the MSC-IP, MSC-IV and P groups at the three weeks after receiving MSCs or placebo. RESULTS: When compared with the control group, ultrafiltration capacity significantly decreased, and the submesothelial thickness increased in the UFF-C and P group, but there were no differences between the control and MSC-IP and MSC-IV groups. The rate of glucose transport was high in the UFF-C and P group compared with the control group, and D/PCr rates in the UFF-C and P group were lower than in the control group. However, D/D0glucose was higher and D/PCr was lower in the MSC-IP group than in the UFF-C and P groups, but D/D0glucose rate of MSC-IV group similar to UFF-C and P groups and there was no difference between MSC-IV group and the other groups in terms of D/PCr rates. The MSC-IP, MSC-IV and P groups had significantly decreased tumor necrosis factor α concentrations compared with the UFF-C group. MSC-IP group had lower levels of TGF-ß1 compared with the P group; MSC-IP group had also lower levels of interleukin-6 compared with UFF-C group. CONCLUSION: The UFF group had a high permeability UFF. These results showed that IV and IP MSC transplantation exerted positive effects on UFF in a chronic rat model of PD. However, healing effect of small solute transport in MSC-IP group was better than MSC-IV group. IP MSC transplantation may be more effective than IV MSC transplantation for the renewal of the peritoneum in chronic PD patients with UFF.

Mesenchymal stem cell transplantation may provide a new therapy for ultrafiltration failure in chronic peritoneal dialysis.

BACKGROUND: The purpose of this study was to investigate possible healing effects of intraperitoneal (IP) mesenchymal stem cell (MSC) transplantation on ultrafiltration failure (UFF) in a chronic rat model of peritoneal dialysis (PD). METHODS: Rats were initially divided into two groups. The APUF group received once-daily IP injections of 20 mL of 3.86% glucose PD solution for 6 weeks to stimulate the development of UFF and a control group received noinjections. The PUF group was sub-divided into three groups: a PUF-C group, an MSC group and a Placebo (P) group. Peritoneal equilibration tests (PETs) and peritoneal biopsies were performed in the control and PUF-C groups. MSCs were administered by IP injection in the MSC group and the PUF-C and P groups received IP injection of placebo. PETs and peritoneal biopsies were performed in the MSC and P groups at the first [P-1 (and MSC-1 groups] and second [P-2 and MSC-2 groups] week after receiving MSCs or placebo. RESULTS: When compared with the control group, ultrafiltration capacity significantly decreased and the submesothelial thickness increased in the PUF-C and P groups (P-1, P-2) (P < 0.05), but there were no differences between the control and MSC groups (MSC-1, MSC-2). The rate of glucose transport was high in the PUF-C and P-2 groups compared with the control group, and D/PCr rates in the PUF-C and P-2 groups were lower than in the control group (P < 0.05). However, D/D0(glucose) was higher and D/P(Cr)was lower in the MSC-2 group than in the PUF-C and P-2 groups (P < 0.05). Transforming growth factor-ß (TGF-ß) levels were lower in the MSC groups than in the P and PUF-C groups (P < 0.05). CONCLUSION: The PUF-C group had a high permeability UFF. These results showed that MSC transplantation exerted positive effects on UFF in a chronic rat model of PD. MSC transplantation may provide new options for the renewal of the peritoneum in chronic PD patients with UFF.

A case of dichorionic twin pregnancy concordant for bilateral cleft lip and palate and discordant for spina bifida; schisis association.

BACKGROUND: The schisis theory suggests that neural tube defect (NTD), cleft lip and palate (CL/P), omphalocele and diaphragmatic hernia are associated to each other more frequently than at the expected random combination rates in a given fetus. However, it is unusual to see schisis-associated defects concordantly in dichorionic twin pregnancy with other schisis-associated and non-associated defects. In addition, the association of lower limb oligodactly with oral cleft and spina bifida has not been reported before. CASE: A 24-year-old woman with twin gestation at 21 weeks was referred to our unit. At ultrasound examination, bilateral CL/P and single umbilical artery in male fetus, and bilateral CL/P and open lumbar spina bifida in female fetus were revealed. At autopsy, oligodactyly of both lower limbs was demonstrated in the female fetus. The parents had no family history of NTD and CL/P. There was no consanguinity, nor was the mother exposed to teratogens.

Pauci-immune crescentic glomerulonephritis caused to dilemma in a patient with suspected systemic lupus erythematosus: a case report.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and there is a distinct differentiation of clinical manifestations. Lupus nephritis (LN) is clinically apparent in approximately half of patients. A kidney biopsy is essential to define the kidney injury, exclude other injurious causes, and determine the histopathologic subtypes. Autoantibodies are crucial to the pathogenesis and the deposition of immune complexes in glomeruli is a hallmark of LN. The histopathology of LN is quite varied. Despite pauci-immune LN being an unexpected condition in SLE, it has been observed rarely with the presence of antineutrophil cytoplasmic autoantibodies (ANCA). We present a young male who was admitted to the emergency with syncope. The brain imaging revealed small infarct areas and signs of cerebral vasculitis. Also, he had elevated inflammatory markers, moderate proteinuria, and preserved kidney function. Anti-nuclear antibodies and anti-dsDNA were positive. Pauci-immune crescentic glomerulonephritis (PICGN) was observed in a kidney biopsy, however, ANCA was negative. SLE diagnosis was established by neurological manifestation, specific antibodies, proteinuria, and kidney biopsy findings. We administered a combination induction regimen, including pulse steroid and parenteral cyclophosphamide. The proteinuria was resolved in the follow-up. Our case highlights that SLE-associated ANCA-negative PICGN can be the initial presentation in the absence of typical manifestations. LN exhibits various pathological mechanisms in the kidney. As a consequence, SLE should be considered in the differential diagnosis of all forms of kidney injury.

Synthesis and antimycobacterial activity of some phthalimide derivatives.

Structurally modified phthalimide derivatives were prepared through condensation of phthalic and tetrafluorophthalic anhydride with selected sulfonamides with variable yields. All compounds were screened for their antimycobacterium activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) using a micro broth dilution technique. The fluorinated derivatives (compounds 2c, 2d, 2f and 2h) had antimycobacterium activity comparable with classical sulfonamide drugs. The minimum inhibitory concentration (MIC) of compounds 2c, 2d, 2f and 2h was greater than that of isoniazid (MIC<0.02 µg/mL) and in vitro activity was greater than that of pyrazinamide, another first line antimycobacterium drug (MIC 50-100 µg/mL). The new compounds could be considered new lead compounds in the treatment of multi-drug resistant tuberculosis.

Modulation of inflammation by mesenchymal stem cell transplantation in peritoneal dialysis in rats.

AIM: The purpose of this study was to determine the effect of mesenchymal stem cell (MSC) transplantation on the peritoneal morphology and inflammation markers in rat models of peritoneal dialysis (PD). MATERIALS AND METHODS: Wistar albino rats were divided into two groups: control (C) (n = 8) and experimental groups (n = 50). PD solution was given to the experimental group during 6 weeks. Then, experimental group was divided into three groups as PD, MSC, and placebo (P) groups. MSC group was treated with MSC (1.5 × 10(6) cells/kg) and P group was treated with phosphate buffer solution via intraperitoneal injection. Evaluation was performed to C and PD groups at the end of 6 weeks and to MSC and P groups at second and third week of the treatment (MSC-2, P-2, MSC-3, and P-3 groups). RESULTS: The submesothelial area was significantly thickened in PD and P groups compared to C and MSC groups. Peritoneal fibrosis was seen in P-3 group but not in MSC group. There were no significant differences between the MSC-3 and C groups according to morphological findings. Levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly increased in MSC-2 group compared to the other groups (p-values ranged from 0.0001 to 0.04). TNF-α and IL-6 levels in MSC-3 and P-3 groups were lower than PD and C groups (p < 0.0001 for TNF-α and p = 0.0001-0.002 for IL-6). CONCLUSION: Giving MSC may protect the peritoneal membrane from the deleterious effect of PD and extend the life of the peritoneal membrane. Our study is the first on this issue and more detailed studies are needed.

Relationship of Gamma-glutamyl Transferase Levels at Diagnosis with Clinicopathological Features in idiopathic IgA Nephropathy.

OBJECTIVE: To compare clinicopathologic features of idiopathic IgA nephropathy in terms of serum gamma-glutamyl transferase (GGT) levels. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Nephrology and Department of Pathology, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey, from January 2010 to January 2021. METHODOLOGY: All patients diagnosed with IgA nephropathy were retrospectively evaluated. Patients were divided into quartiles of gamma-glutamyl transferase. Clinical and pathological features were compared between the groups. RESULTS: A total of 69 patients with idiopathic IgA nephropathy were analysed. The GGT quartiles consisted of Q1(GGT ≤14 U/L) in 18 patients, Q2(GGT = 14.01-20 U/L) in 17 patients, Q3(GGT = 20.1-35 U/L) in 18 patients, and Q4(GGT >35 U/L) in 16 patients. The rates of mesangial cellularity, segmental glomerulosclerosis, and tubular atrophy were found to be significantly different among GGT groups (p= 0.024, p= 0.048, and p<0.001 respectively). Serum albumin and 24-hours proteinuria were also significantly different between groups (p<0.001). CONCLUSION: Gamma-glutamyl transferase may play a role in some clinical and pathological features of IgA nephropathy. KEY WORDS: Gamma-glutamyl transferase, IgA nephropathy, Proteinuria, Serum albumin, Mesangial Cellularity, Segmental glomerulosclerosis, Tubular atrophy.

Acute postinfectious glomerulonephritis with native aorta valve endocarditis and myopericarditis due to brucellosis.

Human brucellosis is a systemic disease that involves multiple organs and tissues concomitantly. In this case, we describe a patient with pancarditis and nephrotic syndrome requiring hemodialyses, which is an unusually fatal condition resulting from brucellosis. He was successfully treated with early aortic valve replacement and intensive medical therapy.

Evaluation of the children with C3 glomerulopathy.

C3 glomerulopathy (C3G) is a clinical spectrum that presents with a variety of symptoms, ranging from a mild disease with asymptomatic microhematuria and/or proteinuria to severe disease with nephritic or nephrotic syndrome and renal impairment. Herein, we aim to document the clinical and laboratory findings, response to immunosuppressive and supportive treatment and prognosis of the children with C3G. We retrospectively reviewed the medical records of patients diagnosed with membranoproliferative glomerulonephritis (MPGN). Kidney biopsy materials were reexamined for the diagnosis of C3G. The inclusion criteria for C3G are the dominant C3 staining with or without scanty immunoglobulins (Ig) deposition on immuno- fluorescence (IF) and MPGN patterns on light microscope. Twelve of 69 patients with MPGN were included in the study based on the definition criteria of C3G. Ten of them had only C3 staining and the rest of the patients had both C3 staining and a small amount of IgG/M staining on IF microscopy. One patient was on remission with only ACEI. The rest of the patients used immunosuppressive treatment and two of them needed eculizumab therapy. One of them did not respond to the treatment of eculizumab and progressed to end-stage renal failure. C3G is a disease characterized by a heterogeneous clinical presentation and outcome. Because of this broad spectrum of disease, treatment may vary widely. We think that complement-targeting therapy with eculizumab should be an alternative option for refractory cases, especially in the early stage of disease, if they did not respond to immunosuppressive treatment.