Unusual benign paratesticular tumor in an infant mimicking rhabdomyosarcoma

Paratesticular tumors are extremely rare, with paratesticular rhabdomyosarcoma being the most common finding. A 6-month-old boy presented with an asymptomatic, right intrascrotal mass whereby the testicle was surrounded by a friable lipomatous tumor. Frozen section revealed an inflammatory process, negative for malignancy. Tumorectomy with vaginal resection was performed, maintaining the testicle and excretory ducts. Histopathologic findings showed a juvenile xanthogranuloma, a non-Langerhans histiocytosis commonly described in infants in the skin and skeletal muscle. The patient is doing well 2 years after surgery and is the first such case reported in the literature with successful conservative treatment.     

右半结肠癌淋巴结转移规律及其临床意义

目的 研究右半结肠癌淋巴转移规律,指导手术根治范围。方法 收集1997年1月至2000年12月根治性切除76例右半结肠癌患的病理资料,按日本结直肠癌临床病理约定（JGR）进行淋巴结分组、分站,分析右半结肠癌的淋巴转移规律。结果 76例患有淋巴结转移49例,转移率64．5％;转移淋巴结184个,转移度17．1％。N1组淋巴结转移率、转移度、阳性淋巴结分布率分别为63．2％、21．5％、53．3％,N2组为39．5％、16．5％、34．2％,N3组为15．8％、9．0％、10．9％,N4组为3．9％、1．5％、1．6％。N1站98个阳性淋巴结沿肠管纵轴分布距肿瘤5cm以内、5－10cm、10－15cm、15－20cm各占68．4％、29．6％、1．0％、1．0％,20cm以上无阳性淋巴结;10cm内外有明显的差异。淋巴转移和结肠癌的组织学类型、浸润深度、肿瘤大小有明显的相关关系。本组发生淋巴结跳跃式转移10例,主要见于组织学分化较差、肿瘤较大、浸润较深,尤其是肿瘤浸润深度达pT3。跳跃式转移的形式以N1（＋）－N2（－）－N3（＋）为主。结论 右半结肠癌淋巴转移主要向中枢方向转移;对低分化癌、肿瘤浸润超过pT3主张把D3式淋巴结廓清作为标准术式;切除结肠肠管的长度以距肿瘤20cm以上为宜。     

Effects of melatonin on spermatogenesis and testicular ischemia-reperfusion injury after unilateral testicular torsion-detorsion

Purpose

This study aimed to determine the effect of melatonin in preventing ischemia-reperfusion (I-R) injury-induced tissue damage and on spermatogenesis after experimental testicular torsion (TT).

Methods

Forty peripubertal rats were divided into 4 groups each containing 10 rats: control (C), sham (S), torsion plus detorsion (TD), and torsion plus melatonin (M). The left testes were rotated 720° for 6 hours and detorsed for 6 hours thereafter. Serum inhibin B (IB) levels were measured in blood samples taken from all groups. Left orchiectomies were performed to determine the tissue levels of Johnsen's scores (JS) and malondialdehyde (MDA).

Results

Serum IB levels in the S and TD groups were significantly lower compared with that in the C group, whereas they were higher in the M group compared with the TD group. The MDA levels were significantly lower in the C, S, and, M groups compared with the TD group. Johnsen's scores were significantly higher in the C, S, and M groups compared with the TD group.

Conclusions

Our results suggested that melatonin is a potent antioxidant agent in preventing testicular I-R injury, as shown by increased IB levels and JS.     

Gradual detorsion of torsioned rat testis attenuates ischemia reperfusion injury

Aim

This study was designed to investigate effect of gradual detorsion on testicular ischemia reperfusion injury.

Materials and Methods

A total of 21 male rats were divided into 3 groups, each containing 7 rats. Torsion was created by rotating the left testis 720° in a clockwise direction. Group 1 underwent sham operation. Group 2 (sudden detorsion) served as a torsion/detorsion group, receiving 2 hours torsion and 2 hours detorsion. In group 3, 360° detorsion was done for 20 minutes after 720° torsion for 2 hours. Then, testis was done full detorsion for 100 minutes. At the end of the experiments (fourth hour), left orchiectomy was performed to measure the tissue levels of malondialdehyde (MDA), superoxide dismutase, and glutathione peroxidase and to perform histologic examination in testes.

Results

The MDA levels of testis tissues were significantly increased in the sudden detorsion group as compared with the sham group. We found decrease of the MDA level in gradual detorsion group, but it was not a statistically significant amount. Significant decrease was found in the superoxide dismutase and glutathione peroxidase activities in the sudden detorsion group as compared with the sham and gradual detorsion groups. Histologic examinations were in accordance with the testicular tissue MDA levels.

Conclusion

In the light of our biochemical and histopathologic findings, we can say that gradual detorsion has a trend to decrease the degree of testicular reperfusion injury in the rat torsion/detorsion model.     

Radiographic and pathological stages of the changes at the bone-cement interface: an in-vivo experimental study

Introduction  Chemical and physical effects of cementation cause radiographic and histological changes at bone-cement interface. These changes can be of interest in the assessment of the residual lesions and subsequent recurrences after local resection and cementation of local aggressive tumours. Aim  The aim of the study was to evaluate the evolution and determine the stages of the changes that occur at the bone-cement interface after cementation of cavitary lesions. Material and methods  We operated on 16 hind legs of 8 sheep (Ovies Aries) under general anaesthesia (Xylasin HCl, Ketamin HCl and Forane). A bone cavity of 12 cm³ was produced by curettage of the distal femoral condyle and was filled with cement. Control radiographs were taken at 2 days; 3, 6 and 12 weeks, and again at 6 months. One sheep each time was killed after second day and sixth month and two sheep each time after the third, sixth and 12th week and the specimens underwent pathological examination. Results  After the first 3 weeks, a reactive fibrous membrane was detected on pathological examinations. This membrane consisted of granulation tissue, necrotic bone and bone marrow, which were replaced gradually by fibrous tissue. The radiographic revelation of this fibrous membrane was a radiolucent zone of 0.5–1.5 mm at 3 weeks. A Sclerotic rim appeared around this radiolucent zone at 6 weeks. With new bone formation the fibrous membrane disappeared at 3 months. This was seen on radiographs as the replacement of the radiolucent zone by a sclerotic ring of 0.5–2 mm. This sclerotic ring disappeared at 6 months, when a diffuse sclerosis and cortical bone thickening was detected on radiographs. Discussion  According to our findings we suggest to consider the pathological processes at the bone-cement interface in 3 phases: (1) Reactive phase (first 3 weeks); (2) Resorption phase (3–6 weeks), and (3) Formation phase (6 weeks to 6 months). We have distinguished five different radiographic stages: Stage 1—Early stage with no apparent zone (first 3 weeks); Stage 2—Radiolucent zone (3–6 weeks); Stage 3—Radiolucent zone with a sclerotic rime (6 weeks to 3 months); Stage 4—sclerotic ring (after 3 months) and Stage 5—Diffuse cortical thickening (after 6 months). Determining the phases of tissue reaction after cementation and its radiographic revelation will ease the diagnosis of residual lesions and subsequent recurrences after local resection and cementation of local aggressive tumors.     

Predictors of renal scar in children with urinary infection and vesicoureteral reflux

We evaluated the predictors of renal scar in children with urinary tract infections (UTIs) having primary vesicoureteral reflux (VUR). Data of patients who were examined by dimercaptosuccinic acid (DMSA) scintigraphy between 1995 and 2005 were evaluated retrospectively. Gender, age, reflux grade, presence/development of scarring, breakthrough UTIs, and resolution of reflux, were recorded. The relation of gender, age and VUR grade to preformed scarring and the relation of gender, age, VUR grade, presence of preformed scarring, number of breakthrough UTIs and reflux resolution to new scarring were assessed. There were 138 patients [male/female (M/F) 53/85]. Multivariate analysis showed that male gender [odds ratio (OR) 2.5], age ≥ 27 months in girls (OR 4.2) and grades IV–V reflux (OR 12.4) were independent indicators of renal scarring. On the other hand, only the presence of previous renal scarring was found to be an independent indicator for the development of new renal scar (OR 13.4). In conclusion, while the most predictive variables for the presence of renal scarring among children presenting with a UTI were male gender, age ≥ 27 months in girls, and grades IV–V reflux, the best predictor of new scar formation was presence of previous renal scarring.     

The common P446L polymorphism in GCKR inversely modulates fasting glucose and triglyceride levels and reduces type 2 diabetes risk in the DESIR prospective general French population

OBJECTIVE— Hepatic glucokinase (GCK) is a key regulator of glucose storage and disposal in the liver, where its activity is competitively modulated, with respect to glucose, by binding to glucokinase regulatory protein (GCKR) in the presence of fructose 6-phosphate. Genome-wide association studies for type 2 diabetes identified GCKR as a potential locus for modulating triglyceride levels. We evaluated, in a general French population, the contribution of the GCKR rs1260326-P446L polymorphism to quantitative metabolic parameters and to dyslipidemia and hyperglycemia risk.RESEARCH DESIGN AND METHODS— Genotype effects of rs1260326 were studied in 4,833 participants from the prospective DESIR (Data from an Epidemiological Study on the Insulin Resistance syndrome) cohort both at inclusion and using the measurements at follow-up.RESULTS— The minor T-allele of rs1260326 was strongly associated with lower fasting glucose (−1.43% per T-allele; P = 8 × 10⁻¹³) and fasting insulin levels (−4.23%; P = 3 × 10⁻⁷), lower homeostasis model assessment of insulin resistance index (−5.69%; P = 1 × 10⁻⁸), and, conversely, higher triglyceride levels (3.41%; P = 1 × 10⁻⁴) during the 9-year study. These effects relate to a lower risk of hyperglycemia (odds ratio [OR] 0.79 [95% CI 0.70–0.88]; P = 4 × 10⁻⁵) and of incident cases during the study (hazard ratio [HR] 0.83 [0.74–0.95]; P = 0.005). Moreover, an additive effect of GCKR rs1260326(T) and GCK (−30G) alleles conferred lower fasting glycemia (P = 1 × 10⁻¹³), insulinemia (P = 5 × 10⁻⁶), and hyperglycemia risk (P = 1 × 10⁻⁶).CONCLUSIONS— GCKR-L446 carriers are protected against type 2 diabetes despite higher triglyceride levels and risk of dyslipidemia, which suggests a potential molecular mechanism by which these two components of the metabolic syndrome can be dissociated.The enzyme glucokinase (GCK) is the major glucose sensor of the pancreatic β-cells, where it adapts insulin secretion to blood glucose levels. GCK also participates in regulating glycogen synthesis and gluconeogenesis in the liver (1). GCK activity is allosterically controlled in hepatocytes by the glucokinase regulatory protein (GCKR), which reversibly binds to GCK and inhibits its activity in the presence of fructose 6-phosphate. GCKR acts as a competitive inhibitor of GCK with respect to glucose and is suppressed by the specific metabolite fructose 1-phosphate (2).In GCKR-deficient mice, the disruption of this regulation and the subsequent decrease in GCK activity leads to altered glucose metabolism and impaired postprandial glycemic control (3,4), although no change in fasting blood glucose concentration is observed. Adenoviral-mediated hepatic overexpression of GCKR in mice with high-fat diet–induced diabetes improves fasting and glucose-induced glycemia and leads to a concomitant increase in insulin sensitivity and triglyceride levels and a decrease in leptin levels (5). Heterozygous mutations in GCK resulting in a reduction of enzymatic activity are responsible for a subtype of monogenic diabetes (maturity-onset diabetes of the young-2) (1,6). Previous genetic studies at the GCKR locus have not reported intragenic mutations associated with type 2 diabetes in humans (7,8).The Diabetes Genetics Initiative (DGI) genome-wide association study for type 2 diabetes and quantitative metabolic traits reported an intronic polymorphism of GCKR (rs780094) explaining interindividual variability in plasma triglyceride (TG) levels and a trend toward association with lower fasting glycemia, less insulin resistance, and lower risk for type 2 diabetes (9). The HapMap II CEU data (www.hapmap.org) showed that rs780094 is in strong linkage disequilibrium (r² = 0.932) with a non-synonymous GCKR variant (Pro446Leu, rs1260326) that we previously identified by the DNA sequencing of French individuals (7). Marju Orho-Melander and colleagues recently communicated their fine-mapping data showing the strongest signal for TG levels at the coding single nucleotide polymorphism (SNP) (rs1260326; P = 1.5 × 10⁻⁹), with lesser associations to fasting glycemia and insulin sensitivity (M. Orho-Melander, O. Melander, V. Lyssenko, for the DGI, unpublished data). Similar findings for the intronic variant rs780094 were reported in a Danish population (10).We evaluated the association between GCKR rs1260326-P446L and TG levels in a middle-aged general French population with a follow-up of 9 years (11). Given the key role of GCKR in hepatic glucose metabolism, we also assessed the effect of rs1260326 on glucose homeostasis parameters and on the risk of impaired fasting glycemia and type 2 diabetes. Furthermore, as we previously showed a strong association of the GCK (−30A) promoter variant (rs1799884) to increased fasting glycemia and type 2 diabetes risk in the same study cohort (11), we also assessed possible additive effects of GCKR rs1260326-P446L and GCK −30G/A SNPs on fasting glucose, insulin, TG levels, and hyperglycemia risk.     

Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma

OBJECTIVES

To analyse the implications of DNA mismatch repair genes hMLH1 and hMSH2 in sporadic renal cell carcinoma (RCC).

MATERIALS AND METHODS

Specimens of tumour and healthy renal tissue were collected from 89 patients treated for sporadic RCC. Another 95 blood samples taken from individuals with no history of cancer were also analysed. After DNA extraction and PCR amplification, microsatellite instability (MSI) was determined using the Bethesda microsatellite panel, two exonic microsatellites of the TGFbRII and BAX genes, and the microsatellite D3S1611. The promoter methylation status of hMLH1 was investigated using the HpaII and MspI restriction enzymes. In addition, a sequencing analysis of complete coding region of hMLH1 and hMSH2 genes was performed.

RESULTS

MSI and promoter hypermethylation of hMLH1 were not detected. Interestingly, loss of heterozygosity (LOH) was common among patients with RCC, particularly in microsatellite D3S1611 (34.9%). Mutations were identified in eight patients: K618A and V716M in gene hMLH1; and I145V, G322D, and the novel mutation P349A, in gene hMSH2. The mutations also appeared in healthy renal tissue and therefore, were considered as germline DNA sequence variations. There were G322D and K618A changes in >1% of the healthy control subjects, suggesting that they are DNA polymorphisms.

CONCLUSIONS

Our data show that loss of function of both hMLH1 and hMSH2 is not involved in sporadic RCC, either by promoter methylation or mutation in their exons. However, LOH indicated that chromosomal instability affecting large fragments of DNA was the main genetic alteration we detected associated with RCC.     

A comparison of the performance of microsatellite and methylation urine analysis for predicting the recurrence of urothelial cell carcinoma, and definition of a set of markers by Bayesian network analysis

OBJECTIVE

To compare the potential of two diagnostic methods for detecting recurrence of urothelial cell carcinoma (UCC) of the bladder, by (i) detecting alterations in microsatellite DNA markers and loss of heterozygosity (LOH), and (ii) detecting aberrant gene hypermethylation, as UCC has a high recurrence rate in the urinary tract and the disease can invade muscle if new tumours are overlooked.

PATIENTS AND METHODS

Over 1 year, urine samples were retrieved from 40 patients already diagnosed with bladder UCC (30 pTa, two pTis, eight pT1). Samples were collected 6 months after bladder tumour resection, during the follow‐up schedule. We used samples to analyse nine microsatellite markers and the methylation status of 11 gene promoters. Receiver operating characteristic curves were generated and Bayesian statistics used to create an interaction network between recurrence and the biomarkers.

RESULTS

During the study, 15 of the 40 patients (38%) had a tumour recurrence and 14 were identified by cystoscopy (reference method). Overall, microsatellite markers (area under curve, AUC 0.819, 95% confidence interval, CI, 0.677–0.961) had better performance characteristics than promoter hypermethylation (AUC 0.448, 0.259–0.637) for detecting recurrence. A marker panel of IFNA, MBP, ACTBP2, D9S162 and of RASSF1A, and WIF1 generated a higher diagnostic accuracy of 86% (AUC 0.92, 0.772–0.981).

CONCLUSION

Microsatellite markers have better performance characteristics than promoter hypermethylation for detecting UCC recurrence. These data support the further development of a combination of only six markers from both methods in urinary DNA. Once validated, it could be used routinely during the follow‐up for the early detection and surveillance of UCC from the lower and upper urinary tract.