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To investigate, along the pituitary- testis- prostate axis, the potential of preoperative serum TT in contributing to defining separate prostatectomy Gleason score (pGS) groups of the prostate cancer (PC) population.The data of 126 patients operated on for PC were retrospectively reviewed. No patient had previously received 5α-reductase inhibitor, luteinizing hormone (LH)-releasing hormone analogs or testosterone replacement treatment. The patient population was grouped according to the prostatectomy Gleason score (pGS) as 6=3+3, 7=3+4, 7=4+3 and 8-10. Twelve variables were simultaneously investigated in each group: age, prolactin (PRL), follicle stimulating hormone (FSH), LH, total testosterone (TT), free testosterone (FT), estradiol (Er), prostate specific antigen (PSA), percentage of prostate biopsy positive cores (P+), biopsy Gleason score (bGS), overall cancer volume estimated as percentage of prostate volume (V+) and prostate weight (Wi). Univariate analysis of variance (ANOVA), multivariate analysis of variance (MANOVA) and multivariate discriminant analysis were the statistical methods used for evaluating the data.There were 38 patients in pGS 6=3+3, 57 in pGS 7=3+4, 15 in pGS 7=4+3 and 16 in pGS 8-10. ANOVA showed that bGS (p0.0001), P+ (p0.0001), V+ (p0.0001), PSA (p=0.02), Wi (p=0.001) and TT (p=0.04) were significantly different in the four pGS groups. MANOVA tests showed that only bGS (p0.0001) and TT (p=0.005) were the significant variables that individually and independently contributed a significant amount to separation of the four pGS groups of the PC population. Multivariate discriminant analysis confirmed that TT (p=0.005) and bGS (p0.0001) were the only variables that independently and significantly contributed to separating the pGS groups.along the pituitary- testis- prostate axis, serum TT is a significant preoperative variable that independently contributes to separating the prostate cancer population into pGS score groups. Pretreatment baseline serum TT levels should be measured for their inclusion in nomograms and future neural networks to be considered in the patient population diagnosed with PC.

To evaluate Luteinizing hormone (LH) physiopathology along the pituitary testicular prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population.Age, percentages of positive cores at Trans Rectal Ultrasound Scan Biopsy (TRUSB) (P+), biopsy Gleason score (bGS), LH, Total Testosterone (TT), Free Testosterone (FT) and Prostate Specific Antigen (PSA) were the continuous clinical variables. All patients had histologically proven carcinoma of the prostate and had not previously received 5α-reductase inhibitors, LH-releasing hormone analogues or testosterone replacement treatment. Correlation analysis was performed for the patient population. Correlation analysis, linear regression and analysis of variance was computed in groups and subgroups of the prostate cancer population.Correlation analysis of the patient population showed that LH was significantly correlated to age (p=0.02) and FT (p=0.01). The population was clustered in LH I (LH≤7.5 IU/l) and LH II (LH7.5 IU/l). Correlation analysis showed significant LH correlations for TT (p0.0001) and FT (p=0.0004) for LH I; significant LH correlation to FT (p=0.0001) for LH II. Simple linear regression showed that LH was significantly predicted by both TT (p-Value0.0001) and FT (p-Value=0.0004) in LH I; but only FT (p-Value0.0001) in LH II. Multiple linear regression showed that LH was significantly predicted by both TT (p-Value=0.0004) and PSA (p-Value=0.03) in LH I; but only by FT (p-Value=0.003) in LH II. Analysis of variance showed that: a) LH and age were significantly lower in LH I than II; b) LH I expressed higher mean FT levels (p=0.08) and lower mean P+ (p=0.07) than LH II. The LH versus PSA plot was computed for LH group I and 3 sub clusters were created: LH I group A (LH/PSA≤0.25), B (0.25LH/PSA ≤0.75), and C (LH/PSA0.75). Correlation analysis showed that LH was significantly correlated to age (p=0.01), TT (p=0.03) and PSA (p=0.0004) in LH IA; LH was significantly correlated to PSA (p0.0001) in LH IB; and LH significantly correlated to TT (p=0.005), FT (p=0.01), and PSA (p=0.008) in LH 1C. Multiple linear regression showed that LH was significantly correlated to age (p=0.02) and PSA (p=0.01) in LH IA, to TT (p=0.01) and PSA (p0.0001) in LH IB, and to PSA (p=0.003) and weakly to TT (p=0.09) in LH IC. The groups differed significantly for mean levels of LH (p=0.0004), TT (p=0.005), FT (p=0.01), PSA (p0.0001), bGS (p=0.003). Analysis of variance between the subgroups of the patient population (LH IA, LH IB, LH IC, LH II) showed significant differences in mean levels for LH (p0.0001), age (p=0.004), TT (p=0.009), FT (p=0.02), PSA (p0.0001), PSA/FT (p0.0001), bGS (p=0.01), but not for P+ (p=0.10).According to LH physiopathology, the prostate cancer population could be clustered into hypo-gonadic and non-hypo-gonadic group at diagnosis. The hypo-gonadic group expresses an aggressive tumor phenotype and might be divided into two more different significant subsets including primary and secondary hypo-gonadic patients: the former (LH II) including older patients with high LH levels, the latter (LH IA) including younger patients with low LH and LH/PSA levels (subgroup LH IA). The non-hypo-gonadic group showed a less aggressive tumor phenotype and according to the LH/PSA ratio might beclustered into LH IB (0.25LH/PSA≤0.75) and LH IC (LH/PSA0.75), the former showing a more aggressive tumor phenotype than the latter. Confirmatory studies are necessary.

To evaluate estradiol (E(2)) physiopathology along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer (PC) and subsequent cluster selection of the patient population.Records of the diagnosed (n=105) and operated (n=91) patients were retrospectively reviewed. Age, percentage of positive cores at-biopsy (P+), biopsy Gleason score (bGS), E(2), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), free-testosterone (FT), prostate-specific antigen (PSA), pathology Gleason score (pGS), estimated tumor volume in relation to percentage of prostate volume (V+), overall prostate weight (Wi), clinical stage (cT), biopsy Gleason pattern (bGP) and pathology stage (pT), were the investigated variables. None of the patients had previously undergone hormonal manipulations. E(2) correlation and prediction by multiple linear regression analysis (MLRA) was performed. At diagnosis, the log E(2)/log bGS ratio clustered the population into groups A (log E(2)/log bGS ≤ 2.25), B (2.25log E(2)/log bGS ≤ 2.48) and C (2.48log E(2)/log bGS ≤ 2.59). The operated population was clustered according to the log E(2)/log pGS ratio into groups A (log E(2)/log pGS ≤ 2.25), B (2.25log E(2)/log pGS ≤ 2.48) and C (2.48log E(2)/log pGS ≤ 2.59). Simple linear regression analysis of bGS and pGS predicting E(2) was computed; differences between the clusters were assessed by analysis of variance (ANOVA) and by contingency tables.At diagnosis, E(2) was correlated to TT (r=0.32, p=0.0006) and FT (r=0.25, p=0.0009); moreover, E(2) was independently-predicted by TT (p=0.009) and bGS (p=0.04) on MLRA. The bGS significantly predicted E(2) in all groups. Groups A, B and C differed in mean values for E(2) (p0.0001), TT (p=0.005), FT (p=0.05), P+ (p=0.01) and bGS (p=0.003); moreover, the frequencies of the different bGPs were significantly different in the three groups (p=0.004). Interestingly, groups A, B, and C were associated with high-, intermediate- and low-bGS tumor grade, as well as with low-, intermediate- and high-serum levels of E(2), TT and FT, respectively. In the operated population, E(2) significantly correlated to FSH (r=-0.20, p=0.04), TT (r=0.34, p=0.0008), FT (r=0.29, p=0.003), bGS (r=0.22, p=0.03) and V+ (r=0.26, p=0.01); moreover, E(2) was independently-predicted by TT (p=0.05) and bGS (p=0.03) on MLRA. The pGS significantly predicted E(2) in all groups that differed for mean values of E(2) (p0.0001), TT (p=0.004), FT (p=0.002) and pGS (p=0.007), as well as for pT (p0.0001) and pGS (p=0.008) frequencies. Interestingly, clusters A, B, and C were associated with high-, intermediate- and low-pGS-pT frequencies as well as with low-, intermediate- and high-mean serum levels of E(2), TT and FT, respectively.In a diagnosed- and operated-PC population, E(2) serum levels were functionally related along the pituitary-testis-prostate cancer axis; also the log E(2)/log bGS and log E(2)/log pGS ratio, clustered the population in three groups where the risk of progression might be ranked as high (group A), intermediate (group B) and low (group C). However, further confirmatory studies are needed.

To evaluate the prolactin hormone (PRL) physiopathology along the pituitary testicular prostate axis at the time of initial diagnosis of prostate cancer and the subsequent cluster selection of the patient population after radical prostatectomy in relation to clinical and pathological variables.Ninety-two operated prostate cancer patients were retrospectively reviewed. No patient had previously received hormonal treatment. The investigated variables included PRL, follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), free testosterone (FT), total prostate specific antigen (PSA), percentage of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), estimated tumor volume in relation to percentage of prostate volume (V+), overall prostate weight (Wi) and age. Empirical PRL correlations and multiple linear predictions were investigated along the pituitary testis prostate axis in the different groups of the prostate cancer population and clustered according to pT (2a/b, 3a, 3b/4) status. The patient population was classified according to the log(10) PRL/V+ ratio and clustered as follows: group A (log(10) PRL/V+ ≤1.5), B (1.5log(10)PRL/V+ ≤2.0) and C (log(10) PRL/V+2.0). Simple linear regression analysis of V+ predicting PRL was computed for assessing the clustered model and analysis of variance was performed for assessing significant differences between the groups.PRL was independently predicted by FSH (p=0.01), LH (p=0.008) and P+ (p=0.06) in low-stage prostate cancer (pT2a/b). Interestingly, PRL was independently predicted by LH (p=0.03) and FSH, TT, FT, PSA, bGS, pGS, V+, Wi and age (all at p=0.01) in advanced stage-disease (pT3b/4). V+ was also significantly correlated (r=0.47) and predicted by P+ (p0.0001) in the prostate cancer population. PRL was significantly correlated and predicted by V+ when the patient population was clustered according to the log(10)PRL/V+ ratio in group A (p=0.008), B (p0.0001) and C (p0.0001). Moreover, the three groups had significantly different mean values of PRL (p0.0001), PSA (p=0.007), P+ (p=0.0001), V+ (p0.0001), Wi (p=0.03), bGS (p=0.008), pGS (p=0.003); also, groups A, B and C had significant different pGS (p=0.03), pT (p=0.0008) and pR (p=0.01) frequency distributions.At diagnosis, in an operated prostate cancer population, PRL was significantly correlated and independently predicted along the pituitary testis prostate axis in high-stage disease; V+ was also significantly correlated and predicted by P+. Because of the high correlation and prediction of PRL by both V+ and P+, the prostate cancer population at diagnosis was clustered according to the log(10)PRL/V+ ratio into groups A, B and C that, in theory, might be models with prognostic potential and clinical applications in the prostate cancer population. However, confirmatory studies are needed.

Oil Red O is a useful tool to assess donor liver steatosis on frozen sections during transplantation. Steatosis is a frequent finding in liver evaluation during transplantation, accounting for 9% to 26% of biopsied donor liver. The degree of macrovesicular steatosis is classified as mild, moderate, and severe; the latter is considered an absolute contraindication to liver transplantation because it is associated with poor allograft outcome. Because of the scarcity of organs, there is a debate whether livers with less severe macrovesicular steatosis are still suitable for transplant. Consequently, tools or methods that allow a more accurate intraoperative assessment of steatosis on frozen sections are mandatory. The aim of this study is to improve intraoperative evaluation of steatosis during transplantation using Oil Red O stain on liver biopsies. Methods Twenty consecutive liver biopsies of donors were collected during transplantation procedures from September 2017 to February 2018 at the Institute of Pathology of the University and Hospital Trust of Verona, Italy. Each liver biopsy was cut at a different thickness (3, 5, and 8 μm) and stained with both Oil Red O and conventional hematoxylin and eosin for intraoperative consultation. The degree (percentage of hepatocytes involved) of fatty changes was recorded. The results obtained during the intraoperative consultation were finally compared with the formalin-fixed and paraffin-embedded permanent section. Results Assessment of steatosis on hematoxylin and eosin frozen sections was reported as mild in 17 cases (85%), moderate in 2 cases (10%) and severe in 1 case (5%). Oil Red O frozen sections reported the following results: mild steatosis in 16 cases (80%), moderate in 2 cases (10%), and severe in 2 cases (10%). The percentage of liver steatosis obtained with Oil Red O was consistent in all cases with that of the permanent sections. The staining procedure for Oil Red O required approximately 18 minutes. Conclusions Oil Red O special stain is a fast and inexpensive tool to improve the assessment of steatosis on frozen biopsies during liver transplantation.

Background: Evidence about the reliability of pre-implantation biopsy is still conflicting, depending on both biopsy type and pathologist’s expertise. Aim of the study is to evaluate the agreement of general v specialist pathologists and to compare scores on biopsy and whole organs in a set of discarded kidneys. Methods: 46 discarded kidneys were identified with their corresponding biopsies. The biopsies were reviewed by three general and two specialist pathologists, blinded to the original report, according to Remuzzi score. The intraclass correlation coefficient (ICC) was calculated for both groups. Discarded kidneys were scored according to Remuzzi score by a single specialist pathologist. Biopsies and organs were compared by Wilcoxon signed rank test. Weighted κ coefficients between biopsy and organ scores were also calculated. Results: Specialist pathologists achieved higher values of ICC, reaching excellent or good agreement in most of the parameters, while general pathologists values were mainly fair or good. On whole organs, scores were consistently lower than biopsies, with a significant difference in most of the parameters. Weighted κ coefficient was slight or fair for most of the parameters. Conclusions: Our data suggests that the creation of a pool of specialist pathologists would improve organ utilization. Moreover, biopsies are not representative of the whole organ. As the Remuzzi score on biopsy is a major reasons for discard, a quota of transplantable kidneys may be erroneously discarded. Refinement in Remuzzi cut-offs based on expert reporting and recognition of sampling error of biopsies in correlation with clinical outcome data should be undertaken.

Background: Diffuse grade II and grade III gliomas are actually classified in accordance with the presence of isocitrate dehydrogenase mutation (IDH-mut) and the deletion of both 1p and 19q chromosome arms (1p/19q codel). The role of tumour grading as independent prognostic factor in these group of tumours remains matter of debate. The aim of this study was to determine if grade is an independent prognostic factor and not somehow associated to IDH mutation and 1p/19q status of the tumour. Methods: We analysed 399 consecutive patients with newly diagnosed, histologically proven World Health Organisation (WHO) 2016 grade II or grade III IDH-mut gliomas, assessed by polymerase chain reaction, immunohistochemistry or next-generation sequencing (NGS). Results: The analysis included 399 patients with grade II (n = 250, 62.7%) or grade III (n = 149, 37.3%) diffuse gliomas. Median follow-up time was 105.3 months. Median survival was 148.1 months. In multivariate analysis, grade II (hazard ratio [HR] = 0.342, 95% confidence interval [CI]: 0.221–0.531; P < 0.001) and 1p/19q codeletion (HR = 0.440, 95% CI: 0.290–0.668; P < 0.001) were independently associated with a lower risk for death. The difference in survival remained significant (p = 0.006 in astrocytomas, p = 0.014 in oligodendrogliomas) when adjusted for histological subtype. Residual disease after surgery (or biopsy) negatively affected survival (HR: 2.151, 95% CI: 1.375–3.367, P = 0.001). Post-surgical treatment with radiotherapy + adjuvant chemotherapy improved survival compared with follow-up and other treatments (HR: 0.316, 95% CI: 0.156–0.641, P = 0.001). Conclusions: In our study, histopathological grade still affects survival in IDH-mutant WHO grade II and III diffuse gliomas. This effect appears to be independent from molecular features, extension of surgical resection and post-surgical treatments. Therefore, physicians should continue to take into account tumour grade, along their molecular characteristics, for a better clinical and therapeutic management of the patients.

BACKGROUND Kidneys with single or multiple tumors, provided that they have histological features recognized as being associated with low risk of recurrence, are considered suitable for transplantation. It is known that kidneys with multiple primary renal tumors show poor renal function and that function dramatically declines when tumors have a miliary configuration. Despite this, no guidelines are in place to differentiate between multifocal tumors and those that are miliary in nature. CASE REPORT We report a case in which initial examination revealed papillary renal cell neoplasia in deceased donor kidneys, which were later confirmed on histological and genetic testing to be multiple and miliary in distribution. Gross examination showed closely opposed neoplasms, and on histological examination these were found to be papillary renal cell carcinomas and renal papillary adenomas. This ultimately led to the decision that both kidneys were unsuitable for transplantation. CONCLUSIONS At present there are no recommendations as to how tumor-bearing donor kidneys should be handled in order to determine if miliary neoplasia is present. From our case it is apparent that, in addition to obvious tumor nodules, at least 3 samples of cortex should be examined. This case highlights the important role of the pathologist in assessing donor kidneys with evidence of neoplasia.

Purpose To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting. Patients and Methods From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m2 of TMZ every 28 days. Chromosome 1p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction. Results The overall response rate was 46.3% (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P = .003). Combined 1p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09). Conclusion TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.

We compared survival in patients with anaplastic astrocytoma (AA) treated with adjuvant procarbazine, lomustine, and vincristine (PCV) with survival in patients treated with temozolomide. A retrospective analysis was made of patients with newly diagnosed AA treated with adjuvant postradiotherapy chemotherapy. Outcome analysis included progression-free survival and overall survival. The following prognostic factors were taken into account: patient age, extent of resection, performance status, presence of contrast enhancement in pre-surgical imaging, and type of adjuvant treatment. Among 109 AA patients, 49 were treated with PCV and 60 with temozolomide. The treatment groups were well matched for pretreatment characteristics, except for the presence of contrast enhancement. Age, extent of surgery, performance status, and presence of contrast enhancement were statistically significant prognostic factors according to the Cox model analysis of survival. Type of adjuvant chemotherapy was not a significant factor, either for progression-free survival or for overall survival. Hematological toxicity, nonhematological toxicity grades 3–4, and premature discontinuation due to toxicity were observed in 9%, 3% to 5%, and 37%, respectively, of cases in the PCV group versus 4% to 5%, 0, and 0, respectively, in the temozolomide group. Although the present study was not randomized, it was well designed, and it reports on two homogeneous and consecutive series of patients, for whom histology was verified to obtain survival data only for patients with AA following the recent WHO 2000 classification. Even if no survival advantage has been demonstrated for temozolomide versus PCV, we conclude that temozolomide should be preferred because of its greater tolerability.

Background The utility of stereotactic brain biopsy (SBB) in AIDS patients still remains controversial. The authors investigated SBB-related diagnostic accuracy, complications, and postoperative sequelae in nonimmunocompromised (NIC) patients and AIDS patients. The role of bioptic yield in treatment planning was also studied in AIDS patients. Methods From 1990-95, 200 computerized tomography (CT) or magnetic resonance imaging (MRI)-guided SBBs were performed in our Department; 172 bioptic procedures were performed in NIC patients (169), and 28 SBBs in AIDS patients (27). The statistical significance was evaluated using the Fisher exact t-test. Results SBB accuracy was very high in both NIC (94.8%) and AIDS (92.9%) patients. Statistical analysis indicated nonsignificant (NS) differences between the two study groups (P > 0.05). Diagnostic yield resulted higher in contrast-enhancing (CE) brain lesions (98.6% in NIC and 95.0% in AIDS patients; P > 0.05; NS), than in non-CE lesions (74.1% in NIC and 87.5% in AIDS patients; P > 0.05; NS). The overall complication rate was similar in both groups (17.2% in NIC and 14.8% in AIDS patients, P > 0.05, NS). The most frequent complication was hemorrhage, with statistically negligible differences between the two study groups (P > 0.05). The frequency of complications involving minor/major morbidity or mortality was very low in NIC (5.9%, 0.6%, and 2.4%, respectively), and in AIDS (3.7%, 7.4%, and 0.0%, respectively) patients. Regarding the therapeutic impact of bioptic diagnosis for neuro-AIDS patients, the preoperative treatment attitude was modified in 23/27 cases (85.2%), and the empiric anti-toxoplasmosis regimen was changed or withdrawn in 17/21 patients (81.0%). Conclusion Our experience demonstrated SBB to be an accurate, manageable, and reasonably safe diagnostic tool in both NIC and AIDS patients. These results suggest also that timely SBB indication in selected AIDS patients, reaching an early diagnosis, may on one side prevent unnecessary and potentially toxic empiric therapeutic regimens, and on the other address the appropriate treatment, thereby improving length and quality of life in such patients.

The frequency of AIDS-associated primary central nervous system (PCNS) lymphoma is rapidly increasing in adults and children. In AIDS-related PCNS lymphoma, different authors have reported an overall poorer response rate to conventional radiation compared with immunocompetent patients. This poorer response consists of a significantly positive, although transient effect on survival following radiotherapy (XRT), with a poor toleration for prolonged whole-brain RT (WBR) and with radiation-induced changes within the normal CNS tissue on autopsy examinations after a course of XRT. These observations led us to consider highly focused single-session radiosurgical treatments as a potentially useful therapeutic modality for AIDS-associated PCNS lymphomas. A multi-institutional diagnostic and therapeutic protocol for the evaluation and treatment of AIDS patients with high-risk intracerebral space-occupying lesions has been developed at the University Hospital of Verona. Therapy is based on tumor biopsy. Tumorsor = 3.5 cm in diameter are subjected to Gamma Knife radiosurgery, whereas tumorsor = 4.5 cm are treated with stereotactic brachytherapy. At the Department of Neurosurgery, Verona, Italy, Gamma Knife treatment was performed in 2 cases of deep-seated histologically verified malignant non-Hodgkin's lymphoma. A short-term cliniconeuroradiological follow-up (2 months later) showed neurologic improvement and virtually complete disappearance of the tumor in both patients. The excellent local control and the well-tolerated single-session treatment and absence of brain toxicity signs on CT scan indicate a putative role for Gamma Knife radiosurgery in the treatment of these patients.