CTLA-4 +49 A/G genotype and HLA-DRB1 polymorphisms in Turkish patients with Henoch–Schönlein purpura

The pathogenesis of Henoch–Schönlein purpura (HSP) remains unknown; however, it is generally considered to be an immune complex-mediated disease. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is expressed on activated T cells, and, thus, it is critically involved in the immune response. We aimed to investigate the possible influence of CTLA-4 polymorphisms for susceptibility to HSP and determine if there were associations with human leukocyte antigen (HLA)-DRB1 genotypes. Using polymerase chain reaction-based DNA genotyping, we investigated the polymorphisms located in the genes encoding CTLA-4 in 100 patients with HSP and 156 ethnically matched healthy controls. When CTLA-4 +49 A/G polymorphism of HSP patients and control group was compared, no associations with joint, gastrointestinal or renal manifestations, or susceptibility to HSP, were observed. However, patients with nephrotic proteinuria had higher HLA-DRB1*13 positivity [odds ratio (OR)?=?3.76, 95% confidence interval (95%CI)?=?1.25–11.23, P?=?0.025]. When the patients were stratified according to CTLA-4 polymorphism, a significant association between nephrotic proteinuria patients and carriage of the AG genotype was also found (OR?=?15.42, 95%CI?=?1.59–148.82, P?=?0.008). These results suggested that CTLA-4 +49 A/G polymorphism does not contribute to susceptibility to HSP; however, the presence of CTLA-4 AG genotype and HLA-DRB1*13 could be a risk factor for developing nephrotic-range proteinuria in these patients.     

Arterial thrombosis associated with factor V Leiden and methylenetetrahydrofolate reductase C677T mutation in childhood membranous glomerulonephritis

Acquired abnormalities of coagulation and fibrinolysis in nephrotic syndrome have been implicated in the pathogenesis of deep-vein and arterial thrombosis. A mutation in the factor V and methylenetetrahydrofolate reductase (MTHFR) gene, the commonest inherited risk factor for venous thrombosis, may contribute to the risk of both arterial and deep-vein thrombosis in patients with nephrotic syndrome. Here, we report on an arterial thrombosis in a young girl with idiopathic membranous glomerulonephritis associated with heterozygous factor V Leiden and homozygous MTHFR C677T mutation. We postulate that screening for factors such as factor V Leiden and MTHFR C677T mutation may be beneficial to patients associated with thromboembolism and idiopathic nephrotic syndrome.     

Current utility of staging laparoscopy for pancreatic and peripancreatic neoplasms

BACKGROUND: The routine use of staging laparoscopy in patients with radiographically resectable pancreatic and peripancreatic neoplasms remains controversial. STUDY DESIGN: We reviewed a prospective database that identified 1,045 patients who underwent staging laparoscopy for radiographically resectable pancreatic or peripancreatic tumors between 1995 and 2005. Radiographic resectability was determined by review of radiographic reports, surgeons' notes, and cross-sectional imaging studies. Factors were assessed for their association with the laparoscopic identification of radiographically occult unresectable disease. Recursive partitioning was used to build a decision tree, with laparoscopic identification of unresectable disease as the outcomes, including only patients since 1999 (modern imaging) and factors available preoperatively. RESULTS: Unresectable disease was identified laparoscopically in 145 of the 1,045 radiographically resectable patients (14%). Factors associated with radiographically occult unresectable disease included the time period of the study, whether imaging was performed at our institution (internal versus external imaging), primary site, histology, weight loss, and jaundice. Primary site (pancreatic versus nonpancreatic) was identified as the strongest predictor of yield. In patients with nonpancreatic tumors, the yield of laparoscopy was 4%. In patients with pancreatic tumors, the yield of laparoscopy was 14% overall, but was 8.4% in patients with internal imaging versus 17% in patients with external imaging (p < 0.01). This higher-risk subgroup was partitioned by the presence of weight loss, then by primary site within the pancreas. CONCLUSIONS: During the time period of this study, the yield of staging laparoscopy decreased and exceeded 10% only for patients with pancreatic adenocarcinoma. When high-quality cross-sectional imaging reveals no evidence of unresectable disease, routine staging laparoscopy may not be warranted for pancreatic or peripancreatic tumors other than presumed pancreatic adenocarcinoma.     

Whole-brain N-acetylaspartate spectroscopy and diffusion tensor imaging in patients with newly diagnosed gliomas: a preliminary study

BACKGROUND AND PURPOSE: Glial cancer cells can be found well beyond the MR imaging T2 signal-intensity hyperintensity. To quantify the extent of the diffuse microstructural tissue damage possibly due to the presence of these satellite tumor cells, we investigated the relationships between global metabolic and microstructural abnormalities in the normal-appearing brain regions of patients with newly diagnosed glioma. MATERIAL AND METHODS: Ten patients (6 men, 4 women) with radiologically suspected untreated supratentorial glial tumors and 9 healthy controls (5 men, 4 women) were studied with T1- and T2-weighted MR imaging, diffusion-weighted echo-planar MR imaging, and whole-brain N-acetylaspartate (WBNAA) proton MR spectroscopy. The relationship between the WBNAA concentration, the mean diffusivity (MD), and fractional anisotropy (FA) values in a large contralateral normal-appearing white matter (NAWM) brain region was investigated with the Spearman rank correlation test. RESULTS: WBNAA values were significantly lower (P < .001) in patients (9.7 +/- 1.7 mmol/L) than controls (13.1 +/- 1.1 mmol/L). MD values were higher (P = .0001) in patients (0.95 +/- 0.07 mm(2)s(-1)) than in controls (0.61 +/- 0.04 mm(2)s(-1)). FA values did not differ between patients (0.42 +/- 0.08) and controls (0.43 +/- 0.041). A strong inverse correlation between WBNAA and MD (r = -0.88, P = .0008) was found in the patients but not in controls (r = 0.012, P = .975). CONCLUSION: The correlation between the WBNAA and MD in the contralateral NAWM suggests that the microstructural damage possibly related to the presence of infiltrative tumor cells contributes to WBNAA decline in these patients.     

The impact of systemic chemotherapy on testicular FDG activity in young men with Hodgkin’s lymphoma

Purpose

Based on prior reports suggesting a positive correlation between fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT and total sperm count and concentration, we sought to identify changes in testicular FDG uptake over the course of chemotherapy in young men with Hodgkin’s lymphoma.

Methods

Fifty-two patients with a mean age of 24.2 years (range 15.5–44.4) at diagnosis monitored with FDG PET/CT to assess treatment response for Hodgkin’s lymphoma were selected for this retrospective analysis under an Institutional Review Board waiver. Of the patients, 26 were treated with a chemotherapy regimen known to cause prolonged and sometimes permanent azoospermia (BEACOPP—bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) and 26 with a regimen known to have a much milder effect on gonadal function (ABVD—doxorubicin, bleomycin, vincristine, and dacarbazine). Each patient underwent one FDG PET/CT before treatment and at least one FDG PET/CT after start of chemotherapy. In all examinations, FDG activity was measured in the testes with different quantification metrics: maximum standardized uptake value (SUV_max), SUV_mean, functional volume (FV) and total testicular glycolysis (TTG), and blood pool activity determined (SUV_mean).

Results

Testicular FDG uptake (SUV_max) was significantly associated with blood pool activity (p?<?0.001). Furthermore, testicular FDG uptake metrics incorporating volume (e.g., FV and TTG) were associated with age. There was no significant change in SUV_max, SUV_mean, FV, and TTG from the PET/CT at baseline to the PET/CTs over the course of chemotherapy either for patients treated with BEACOPP or for patients treated with ABVD.

Conclusion

For patients undergoing chemotherapy for Hodgkin’s lymphoma, there is a significant association between testicular FDG uptake and blood pool activity, but no significant changes in FDG uptake over the course of chemotherapy. Therefore, FDG uptake may not be a feasible surrogate marker for fertility monitoring in patients with Hodgkin’s lymphoma undergoing chemotherapy.     

Profile of Plasma Angiogenic Factors Before and After Hepatectomy for Colorectal Cancer Liver Metastases

Background Circulating angiogenic factors in patients with colorectal cancer liver metastases may promote tumor growth and contribute to liver regeneration after partial hepatectomy. Methods We analyzed blood samples from 26 patients with colorectal cancer liver metastases before and after liver resection and used samples from 20 healthy controls as a reference. Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and hepatocyte growth factor (HGF) were measured, and levels were correlated with recurrence. Results The median preoperative levels of all four factors were significantly higher and more variable in colorectal cancer liver metastasis patients than in controls. HGF and bFGF levels increased significantly 3 days and 1 month after hepatectomy, respectively, and returned to near preoperative levels at 3 months. Postoperative VEGF and EGF levels remained relatively stably increased over 3 months. After a median follow-up of 19 months, 10 patients (42%) experienced recurrence. Higher preoperative VEGF and HGF levels correlated with subsequent recurrence (P = .018 and .021, respectively), and a preoperative adjusted total value of all four factors accurately identified patients at low, moderate, and high risk of recurrence (P = .034). Patients who experienced disease recurrence also had relatively higher bFGF levels 3 months after operation (P = .035). Conclusions Plasma angiogenic factors are increased in patients with colorectal cancer liver metastases and remain increased at least 3 months after partial hepatectomy. Measurement of certain factors before and after hepatic resection can predict recurrence. Targeted biological agents may counteract the tumor-promoting effects of these circulating factors on subclinical disease.     

Triphalangeal Thumb with Polydactyly: An Alternative Surgical Method

Triphalangeal thumb (TPT) is congenital hand anomaly which a thumb consists of three phalanges. Thumb appearance can differ widely; the thumb can be longer than usual or it can be deviated in the radio-ulnar plane. Thumb strength and function can be significantly diminished. The goals of surgical treatment are to reduce the elongated thumb length, establish normal thumb function, maintain a stable joint and improve thumb position if necessary. In general, surgical treatment is performed for improvement of thumb function. The case presented here had a TPT with pre-axial polydactyly. The TPT was well developed but it had no movement at the proximal or distal interphalangeal joints. The rudimentary thumb had a well-developed and functioning interphalangeal (IP) joint. So as an alternative surgical technique we planned to transfer the functioning IP joint of rudimentary thumb to the TPT.     

ACE Gene Polymorphism in Turkish Children with Nephrotic Syndrome

Since 1990, the role of angiotensin converting enzyme (ACE) gene polymorphism in various renal and cardiac diseases is still debated. This study comprised 71 pediatric patients with nephrotic syndrome, 47 males (66%) and 24 females (34%) with a mean age of 57.4 ± 37.6 months, and a control group of 83 healthy males (59%) and 57 healthy females (41%) with a mean age of 505 ± 160.5 months. The distribution of the ACE genotype in the control group was II, 11%; ID, 53%; and DD, 36%, and the nephrotic syndrome was II, 4%; ID, 78%; and DD, 18%. Angiotensin-converting enzyme genotypes were significantly different between patients and control groups (p<0.05). The study groups consisted of 52 (73%) with steroid-sensitive nephrotic syndrome (SNSS) and 19 (27%) with steroid-resistant nephrotic syndrome (SRNS). The distribution of the ACE genotype was II, 6%; ID, 75%; and DD, 19% in the SSNS population and ID, 84% and DD, 16% in the SRNS population. No statistically significant difference was found between steroid sensitivity and ACE genotypes (p=0.5). The results show that ACE I/D polymorphism does not contribute to the steroid resistance, even though this study indicates that the presence of the I/D genotype has a much higher risk—approximately 2.8 times—of having nephrotic syndrome. Further studies with a larger number of patients are needed.     

Association of Positive Transection Margins with Gastric Cancer Survival and Local Recurrence

Purpose

To examine the association between positive resection margins and survival and local recurrence in patients with gastric cancer undergoing resection with curative intent.

Methods

Patients who underwent curative intent resection for gastric carcinoma from 1985 to 2010 were identified from a prospectively maintained database. Positive margins were defined as disease present at the line of luminal transection. Clinicopathological features and outcome of patients undergoing gastrectomy with negative and positive margins were compared.

Results

Among 2384 patients undergoing curative intent resection, 108 (4.5 %) had positive margins. Positive margins were associated with higher American Joint Committee on Cancer (AJCC) stage, T stage, N stage, median number of positive nodes, diffuse Lauren type, and poorly differentiated tumors. Treatment of positive margins consisted of: observation (39 %), chemoradiotherapy (26 %), chemotherapy (20 %), repeat resection (10 %), radiotherapy (4 %), and unknown (1 %). Multivariate analysis of the entire cohort demonstrated margin status, T stage, N stage, grade, and perineural invasion to be independent predictors of survival. Margin status was an independent predictor of survival in patients with ≤3 positive nodes or T1–2 disease but was not in patients with >3 positive nodes or T3–4 disease. Local recurrence occurred in 16 % of patients with a positive margin. We identified no factors predictive of local recurrence in patients with positive margins.

Conclusions

Positive resection margin is associated with advanced AJCC stage and aggressive tumor biology but remains an independent predictor of worse survival. The significance of a positive margin in gastric cancer is confined to patients with nontransmural disease and/or limited nodal involvement.

     

Clinical nodal staging scores for bladder cancer: a proposal for preoperative risk assessment

Background

Radical cystectomy (RC) with pelvic lymph node dissection (LND) is the standard of care for refractory non-muscle-invasive and muscle-invasive bladder cancer. Although consensus exists on the need for LND, its extent is still debated.

Objective

To develop a model that allows preoperative determination of the minimum number of lymph nodes (LNs) needed to be removed at RC to ensure true nodal status.

Design, setting, and participants

We analyzed data from 4335 patients treated with RC and pelvic LND without neoadjuvant chemotherapy at 12 academic centers located in the United States, Canada, and Europe.

Measurements

We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed clinical (preoperative) nodal staging scores (cNSS), which represent the probability that a patient has LN metastasis as a function of the number of examined nodes.

Results and limitations

The probability of missing a positive LN decreased with an increasing number of nodes examined (52% if 3 nodes were examined, 40% if 5 were examined, and 26% if 10 were examined). A cNSS of 90% was achieved by examining 6 nodes for clinical Ta-Tis tumors, 9 nodes for cT1 tumors, and 25 nodes for cT2 tumors. In contrast, examination of 25 nodes provided only 77% cNSS for cT3-T4 tumors. The study is limited due to its retrospective design, its multicenter nature, and a lack of preoperative staging parameters.

Conclusions

Every patient treated with RC for bladder cancer needs an LND to ensure accurate nodal staging. The minimum number of examined LNs for adequate staging depends preoperatively on the clinical T stage. Predictive tools can give a preoperative estimation of the likelihood of nodal metastasis and thereby allow tailored decision-making regarding the extent of LND at RC.