p53 mutations in gastric and colorectal cancers in Texas Hispanics versus Anglos

Gastric cancer is more than twice as common in Hispanics as in Anglos in Texas, while colorectal cancer is almost twice as common in Anglos as Hispanics. To test the hypothesis that mutations in the p53 tumour suppressor gene are involved in these differences, we examined 131 gastric and 138 colorectal cancers from Hispanic and Anglo patients from South Texas and Mexico using immunohistochemistry (IHC) as a screening assay for p53 mutations. The fraction of p53 positive cases was not significantly different in gastric cancers from Hispanics compared to Anglos (43% versus 61%, respectively, p=0.13) or in colorectal cancer (57% versus 58%, respectively, p=1.0), suggesting that p53 mutations are not involved in causing the different incidences of these cancers in these populations. In addition, the types of p53 mutations arising in gastric tumours from Hispanic patients were consistent with those reported in gastric tumours in other populations. Sequencing of mutations in five gastric cancers revealed two G: C to A: T transitions, two A: T to G: C transitions and one complex deletion. In contrast with findings in studies in other tumour types, neither stage nor survival was associated with p53 positive staining by IHC in either gastric or colorectal tumours in this study. Positive p53 immunostaining was associated with the diffuse histological subtype in gastric carcinoma (p=0.05) and high histological grade in colorectal carcinoma (p=0.04).     

Prognostic indicators in WHO 2003 low‐grade endometrial stromal sarcoma

Aims: Endometrial stromal sarcoma (ESS) has traditionally been divided into low and high grade, but the World Health Organization (WHO, 2003) has changed the definition. Since 2003, many studies have used the old criteria, and few have focused on WHO 2003‐defined ESS low grade (ESS‐LG). The aim of this study was to investigate prognosticators in ESS‐LG. Methods and results: We reviewed the WHO 2003 diagnostic criteria in 91 tumours (previously classified as ESS low and high grade). There were 68 cases of ESS‐LG and 23 of undifferentiated endometrial sarcoma (UES). In the ESS‐LG cases, the prognostic value of clinicopathological variables was studied. With a median follow‐up of 79 months (range: 20–474 months), the recurrence and death rates were 5/68 (7%) and 1/68 (1.5%) in the ESS‐LG cases. Ovarian preservation or no ovarian preservation (P < 0.0001, hazard ratio (HR) 10.4) and mitotic activity index (MAI) (0–3 versus >3, P = 0.005, HR 8.6) had independent prognostic value. Other frequently used MAI thresholds – age, tumour diameter, and vessel invasion – were not prognostic. Among patients without ovarian preservation (n = 61), none of 53 with MAI 0–3 suffered recurrence, contrasting with two of eight (25%) of those with MAI >3 (P = 0.003); one of these two recurrence patients died (P = 0.02). Among patients with ovarian preservation (n = 7), three (43%) suffered recurrence but none died, and MAI had no additional prognostic value. Conclusions: In ESS‐LG, ovarian preservation and MAI >3 are associated with increased risk of recurrence.     

Urbanization,migration, and indigenous health in Peru

Introduction

We compare demographic, socioeconomic, and anthropometric characteristics and blood pressure (BP), between rural and urban Peruvian indigenous women. These are preliminary results from a project on urbanization, migration, and health.

Methods

Data were collected cross-sectionally (2019) and compared between a rural (n = 92) and an urban (n = 93) community.

Results

Height: μ = 148.3 ± 5.0 cm (range = 137–162), weight: μ = 62.0 ± 11.5 (range = 37.5–108.7), median waist circumference = 89.0 (IQR = 15.8, range = 64.0–126.0), BMI = 28.3 (IQR = 6.2, range = 16.7–40.0), with no significant rural–urban differences. Systolic but not diastolic BP was significantly higher in urban versus rural women (median = 110, IQR = 18, range = 80–170 vs. median = 120, IQR = 10, range = 90–170, p = .002 and median = 70, IQR = 17, range = 50–100 vs. median = 70, IQR = 10, range = 60–100, p = .354), respectively.

Conclusions

Despite major lifestyle differences, there were no anthropometric differences between rural and urban women. Higher systolic BP in urban women may reflect social/economic stressors rather than dietary factors.     

A20 deletion is associated with copy number gain at the TNFA/B/C locus and occurs preferentially in translocation‐negative MALT lymphoma of the ocular adnexa and salivary glands

The genetic basis of MALT lymphoma is largely unknown. Characteristic chromosomal translocations are frequently associated with gastric and pulmonary cases, but are rare at other sites. We compared the genetic profiles of 33 ocular adnexal and 25 pulmonary MALT lymphomas by 1 Mb array–comparative genomic hybridization (CGH) and revealed recurrent 6q23 losses and 6p21.2–6p22.1 gains exclusive to ocular cases. High‐resolution chromosome 6 tile‐path array–CGH identified NF‐κB inhibitor A20 as the target of 6q23.3 deletion and TNFA/B/C locus as a putative target of 6p21.2–22.1 gain. Interphase fluorescence in situ hybridization showed that A20 deletion occurred in MALT lymphoma of the ocular adnexa (8/42 = 19%), salivary gland (2/24 = 8%), thyroid (1/9 = 11%) and liver (1/2), but not in the lung (26), stomach (45) and skin (13). Homozygous deletion was observed in three cases. A20 deletion and TNFA/B/C gain were significantly associated (p < 0.001) and exclusively found in cases without characteristic translocation. In ocular cases, A20 deletion was associated with concurrent involvement of different adnexal tissues or extraocular sites at diagnosis (p = 0.007), a higher proportion of relapse (67% versus 37%) and a shorter relapse‐free survival (p = 0.033). A20 deletion and gain at TNFA/B/C locus may thus play an important role in the development of translocation‐negative MALT lymphoma. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Analysis for loss of heterozygosity on chromosome arm 13q by STR analysis or SNP sequencing can replace analysis of FLT3‐ITD to detect patients with prognostically adverse AML

We aimed at developing novel assays for Loss of Heterozygosity (LOH) detection on 13q as a substitute for FLT3‐ITD analysis to identify acute myeloid leukemia (AML) patients with high risk of shorter survival. To this aim, we first analyzed a selected cohort of 185 patients with (n = 138) or without (n = 47) FLT3‐ITD by short tandem repeat (STR) analysis for 13q LOH. In 46 of 138 FLT3‐ITD positive cases, a FLT3‐ITD/FLT3wt ratio of ≥1 was measured indicating LOH. Applying analysis with a combination of five different STR markers, a threshold of an STR allelic ratio of >65% allows the identification of LOH in 40/46 (87%) samples. Survival analysis revealed significantly inferior outcome in patients with LOH as detected by STR analysis (event free survival (EFS): no LOH: 13.3 months versus LOH: 4.5 months, p < 0.001; overall survival (OS): no LOH: 35.8 months versus LOH: 9.7 months, p = 0.001). In multivariate Cox regression analysis, 13q LOH was found to be an independent adverse parameter for EFS and OS (p = 0.003 and p < 0.001, respectively) besides age and white blood cell count. Thus, the prognostic impact of 13q LOH is nearly identical to the one of FLT3‐ITD/FLT3wt load of ≥1 and thus is a feasible alternative to identify respective patients with high risk AML. In a second approach, a cohort of 91 patients was subjected to a proof‐of‐principle study of applying single nucleotide polymorphism analysis by next generation amplicon sequencing for detection of LOH. 53/91 cases had LOH and 50 were identified with this new method resulting in a positive detection rate of 94.3%. © 2014 Wiley Periodicals, Inc.     

Significance of liver histology in HBsAg‐positive,IgM anti‐HBc‐negative acute hepatitis B virus‐related hepatitis

Delladetsima I, Papatheodoridis G V, Tiniakos D G, Hatzakis A & Tassopoulos N C
(2012) Histopathology  61, 881–888 Significance of liver histology in HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus‐related hepatitis Aims: The natural course of HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus (HBV)‐related hepatitis is unclear. The aim of this study was to evaluate the prognostic significance of histological features and hepatic expression of HBV antigens in such patients. Methods and results: Fifty patients with HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B who underwent liver biopsy during the acute hepatitis episode were studied [HBeAg seroconversion (n = 16), persistently positive for HBeAg (n = 9), and persistently negative for HBeAg (n = 25)]. Twenty‐six cases had features of typical acute hepatitis only (group A), and 24 cases had changes suggesting pre‐existing chronic hepatitis (group B). HBcAg and/or HBsAg immunoreactivity was detected less frequently in group A than in group B (31% versus 79%, P = 0.01). HBsAg clearance was observed in 24% of patients, almost exclusively in cases with HBeAg seroconversion. HBsAg loss was significantly more frequent in group A than in group B (52% versus 0%, P < 0.001), and in cases without rather than with immunohistochemical expression of HBV antigens (55% versus 0%, P < 0.001). In group A, HBsAg clearance was observed in 80%, 54% and 0% of patients with mild, moderate or severe acute hepatitis, respectively (P = 0.034). Conclusions: Histological information is very important for the prognosis of HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B. HBeAg seroconversion with underlying typical acute hepatitis changes of mild to moderate severity without hepatic expression of HBV antigens strongly predicts subsequent HBsAg loss.     

Prognostic value of cells with more than 5c DNA content in node-negative breast cancer as determined by image cytometry from tissue sections

The aim of this investigation was to study the prognostic significance of 5c cells (presence of cancer cells with >5c DNA content; ie, over 18 pg of DNA per nucleus) in axillary node-negative breast cancer. Tissue sections (3 μm) from 134 tumors were stained for DNA using the Feulgen method and screened for the percentage of 5c cells with the CAS 200 image analysis system (Cell Analysis System, Inc, Lombard, IL). Cancer cells with a DNA content exceeding the 5c level were found in 45% (60 of 134) of the cases, accounting for a median of 0.2% (range, 0.05% to 1.05%) of all cells. The presence of 5c cells was associated with a high histologic grade of the tumor (P = .0001), a large number of mitoses (P < .0001), flow cytometric DNA aneuploidy and high S-phase fraction (P = .0002 and P < .0001, respectively), and c-erbB-2 oncoprotein and p53 tumor suppressor gene product overexpression (P = .0002 and P = .0006, respectively). Patients with 5c cell-positive tumors had a significantly worse 8-year survival rate (P = .003) than those with 5c cell-negative tumors. Subgroup analysis showed that the presence of 5c cells had a prognostic impact in low malignancy tumors, ie, in well-differentiated (grade I or II) and slowly proliferating tumors. Our findings suggest that determination of 5c cells may be a useful additional prognostic factor in axillary node-negative breast cancer. It adds prognostic information, especially in cases that are otherwise thought to have a favorable course.     

Adrenocorticotropin-Producing Pituitary Carcinoma with Expression of c-erbB-2 and High PCNA Index: A Comparative Study with Pituitary Adenomas and Normal Pituitary Tissues

Pituitary carcinomas are very rare neoplasms with a poor prognosis. We report a case of Cushing’s disease resulting from a pituitary carcinoma in a 22-yr-old female, who died of massive hepatic failure. At autopsy, there was invasion of the parasellar structures and vasculature by the tumor, which stained positively only for ACTH. There were two metastatic nodules in the liver, which also stained positively for ACTH. When compared to other cases of Cushing’s disease (n = 52), other pituitary adenomas (n=292), and normal pituitary tissues (n = 21), the pituitary carcinoma was the only one withc-erbB-2 membrane staining in both the sellar-located tissue and liver metastasis.C-erbB-2 staining was present in the cytoplasm of a variable number of cells in 40% of the invasive adenomas (n = 103), while only 1.2% of the noninvasive tumors (n = 241) expressed this protein (p < 0.001). No particular immunohistological type preferentially expressed this protein. In normal pituitary tissues, 10% of the cells expressed cytoplasmicc-erbB-2. A higher index of proliferating cell nuclear antigen (PCNA) in the primary tumor and liver metastasis (10%) was also found compared to other ACTH-secreting adenomas (invasive, 3.4±1.9% vs 1.7±1.5% in noninvasive) and other pituitary tumors (invasive, 2.9±1.5% vs 1.5±1.3% in noninvasive). The PCNA index was significantly higher in invasive tumors than in noninvasive adenomas (p = 0.004). PCNA staining was negative in normal pituitary tissues. Staining for p53, pRB and p^21ras was negative in the carcinoma and liver metastasis. We suggest that thec-erbB-2 membrane pattern and a higher PCNA index may indicate a worse prognosis in adenohypophyseal neoplasia.     

Array‐CGH predicts prognosis in plasma cell post‐transplantation lymphoproliferative disorders

Plasma‐cell post‐transplantation lymphoproliferative disorder (PC‐PTLD) is a rare monomorphic PTLD entity divided into plasma cell myeloma (PCM) and plasmacytoma‐like lesion (PLL) PTLD. To date, there are no exhaustive published cytogenetic data on PC‐PTLD. We report array‐based comparative genomic hybridization (aCGH) of 10 cases of PCM and PLL‐PTLD. Patients had received kidney (n = 6), heart (n = 2), lung (n = 1) or bone marrow (n = 1) transplantation. There were six men and median age at time of PTLD was 56.5 years (3–74). We identified two different cytological features, plasmacytic and plasmablastic, among six PLL and three PCM PTLD. Eight cases were associated with EBV. First line treatment was heterogeneous: rituximab alone (n = 5), CHOP‐like (n = 3) and multiple myeloma‐like (n = 1). One patient died before any treatment. After a median follow‐up of 19.5 months (0–150), five patients died (four from PTLD) and five were alive without evidence of disease. By aCGH, 5/10 demonstrated a complex profile. The most frequent abnormalities were +7q (5/10), +16q (5/10), +17q (5/10), +17p (4/10), +5q (4/10), t7 (4/10), t9 (3/10), del1p (3/10). No del17p13 (TP53) were observed. Del1p32.3 (CDKN2C) was observed in 2 cases. On univariate prognostic analysis, a complex aCGH was associated with a shorter OS. Thus, cytogenetic abnormalities seem to be closely related to those reported in multiple myeloma or diffuse large B cell lymphoma. Complex aCGH constitutes an unfavorable prognostic marker and aCGH should be integrated in the evaluation of patients with PLL/PCM‐PTLD. © 2016 Wiley Periodicals, Inc.     

Tumour budding and a low host inflammatory response are associated with a poor prognosis in oesophageal and gastro‐oesophageal junction cancers

Brown M, Sillah K, Griffiths E A, Swindell R, West C M, Page R D, Welch I M & Pritchard S A
(2010) Histopathology 56, 893–899
Tumour budding and a low host inflammatory response are associated with a poor prognosis in oesophageal and gastro‐oesophageal junction cancers Aims: Tumour budding and host inflammatory response are parameters easily assessed histologically that have prognostic significance in many cancers. There have been few studies examining these parameters in oesophageal or gastro‐oesophageal cancers. This study aims to address that deficiency. Methods and results: A two‐centre, retrospective study was carried out on 356 patients. Tumour budding and host inflammatory response at the invasive front were assessed histologically. Statistical analysis was performed to determine the prognostic significance of these factors. The median number of tumour buds was four (range 0–50) with 172 of 356 cases having five or more buds at the invasive front. The presence of five or more buds was associated with a poor prognosis on univariate analysis (P = 0.0001), as was a sparse or moderate host inflammatory response (P = 0.001). Tumour budding retained prognostic significance when tumours were separated into adenocarcinomas (n = 287) and squamous cell carcinomas (n = 69), but host inflammatory response was a significant prognostic factor only for adenocarcinomas. On multivariate analysis the presence of five or more buds retained significance (P = 0.002). Conclusions: Tumour budding and host inflammatory response are important prognostic factors in patients with oesophageal/gastro‐oesophageal cancer and can be used to identify high‐risk patients who would benefit from closer follow‐up and adjuvant therapies.     

Prognostic role of SPARC expression in gastric cancer: a meta-analysis

Introduction

Secreted protein acidic and rich in cysteine (SPARC) is involved in regulating cell adhesion, proliferation, migration, and tissue remodeling. We performed a meta-analysis to evaluate the association between SPARC expression and the clinicopathologic features and outcomes of gastric cancer patients.

Material and methods

Publications that assessed the clinical or prognostic significance of SPARC in gastric cancer up to October 2013 were identified. A meta-analysis was performed to clarify the association between SPARC expression and clinical outcomes.

Results

Ten studies, including 1417 cases, met the inclusion criteria. The data were analyzed and the results show that SPARC is not significantly associated with the depth of gastric cancer invasion (odds ratio (OR) = 1.17, 95% confidence interval (CI): 0.60–2.29, Z = 0.47, p = 0.64) or tumor differentiation (OR = 0.59, 95% CI: 0.22–1.58, Z = 1.06, p = 0.29). Moreover, SPARC was not significantly correlated with lymph node metastasis (OR = 0.72, 95% CI: 0.37–1.41, Z = 0.96, p = 0.34). However, SPARC overexpression was highly correlated with reduced overall survival (relative risk (RR) = 1.78, 95% CI: 1.52–2.09, Z = 7.10, p = 0.43).

Conclusions

The SPARC may play an important role in the progression of gastric cancer, and SPARC overexpression is closely correlated with poor patient survival. The SPARC is a potential clinical marker for the survival of gastric cancer patients; however, well-designed prospective studies are needed to confirm these findings.     

Comparison of quantitative and classic prognosticators in urinary bladder carcinoma

Summary The prognostic value of nuclear morphometry and DNA flow cytometry of paraffin embedded material of 58 patients with primary and untreated transitional cell carcinoma of the bladder was compared with that of histological grade (WHO-system), tumour stage (TNM-classification), tumour size, multiplicity and ulceration. Small nuclear size (mean nuclear area 95 µm²) (n=25) and DNA diploidy (n=28) indicated a favourable outcome (5-year survival 95.8% and 92.2%); large nuclei (mean nuclear area > 95 µm²) (n=33) and DNA aneuploidy (n=30) indicated a worse prognosis (5-year survival 61.4% and 62.5%) (Mantel-Cox:p=0.002 andp=0.007). The quantitative techniques had the advantage over subjective histological grading that distinguishment of an intermediate patient group (WHO-system: grade 2;n= 32) with heterogeneous outcome (5-year survival 78%) was avoided. Multivariate analysis showed tumour stage as the most important prognosticator of survival. Neither the quantitative techniques, nor the other classic features added significantly to the prediction. The additional value of the quantitative techniques was however shown in superficial carcinoma (TNM-classification: stage Ta and T1;n=37): large nuclei (mean nuclear area > 95 µm²) (n= 15 ) and aneuploid DNA peaks (n=13) were associated with progressive recurrent tumour (n=7) (Mantel-Cox:p= 0.03 andp=0.0004). The quantitative methods thus indicate which patients are at risk for progression and may enable more appropriate treatment at an earlier stage of disease.     

The length of positive surgical margins correlates with biochemical recurrence after radical prostatectomy

van Oort I M, Bruins H M, Kiemeney L A L M, Knipscheer B C, Witjes J A & Hulsbergen‐van de Kaa C A
(2010) Histopathology 56 , 464–471 The length of positive surgical margins correlates with biochemical recurrence after radical prostatectomy Aims: To evaluate the prognostic role of the length of a positive surgical margin (+SM) for biochemical recurrence (BCR) after radical prostatectomy (RP) for prostatic cancer. Methods and results: Consecutive RP specimens (n = 267) with +SM were analysed. All RP specimens were sectioned at 4‐mm intervals and completely embedded. Data were analysed using Kaplan–Meier survival analysis and proportional hazards models. In 267 patients the length of +SM ranged from 0.4 to 174.5 mm (median 11.2 mm) and correlated with preoperative prostate specific antigen (PSA) (P < 0.001), pathological stage (P < 0.001), tumour volume (P = 0.001), number of +SM (P < 0.001), Gleason grade at +SM (P < 0.001) and Gleason score (P = 0.015). Patients with detectable postoperative PSA levels (n = 34) or adjuvant therapy (n = 59) were excluded from BCR analysis. In the remaining 174 patients the 5‐year risk of BCR was 29%; in patients with +SM ≤10 mm and >10 mm this was 21% and 39%, respectively. On multivariable analysis BCR was associated with an increasing length of +SM (≤10 mm versus >10 mm; hazard ratio 2.15; 95% confidence interval 1.12, 4.15; P = 0.022). Conclusions: The length of +SM is an independent prognostic factor for BCR in patients with undetectable PSA after RP.     

Reduced IFN-γ Responses Associated with HLA-DR15 Presentation of Streptococcal Cell Wall Proteins to Dermal Th-1 Cells in Psoriasis

We have recently described a group A streptococcal (GAS)-reactive Th-1 subset specifically present in skin lesions of chronic plaque psoriasis. To investigate MHC presentation of GAS cell wall proteins, dermal T cell lines (TCL) cultured from the lesional skin of 39 HLA-typed psoriasis patients were stimulated with a cell wall extract, stained for intracellular IFN- expression, and analyzed by flow cytometry. TCL from a further seven psoriasis patients were also tested with S. mutans extract. Eight TCL were tested in the presence of anti-Class II antibodies or allogeneic antigen-presenting cells. The dermal T cell IFN- responses to the cell wall extract, which ranged from <1 to 28%, were significantly higher than that to S. mutans extract (p = 0.0052) and were self-HLA-DR allele restricted. A significantly decreased response was observed in TCL from DR15⁺ (n = 13) versus DR15^– (n = 26) patients (p = 0.0377). In addition, DR15⁺ patients had a later age of onset of disease and a decreased history of sore throats. In contrast, TCL from HLA-DR7⁺ (n = 23) patients responded similarly to those from individuals lacking the DR7 allele. However, DR7⁺ patients who coexpressed the MHC Class I antigen, Cw6 (n = 14) had a significantly higher IFN- response than Cw6^–, DR7⁺ patients ( n = 7; p = 0.0288) whose responses were also significantly lower than those of patients expressing non-DR7 alleles (n = 16; p = 0.0302). This study has shown that HLA-DR15 expression is associated with a reduced dermal Th-1 response to GAS cell wall proteins in patients with psoriasis. It is proposed that HLA-DR allelic variation may contribute to disease phenotype via effects on the immune response to group A streptococci.     

Downregulated parafibromin expression is a promising marker for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas

Parafibromin is a protein encoded by the hyperparathyroidism 2 oncosuppressor gene and its downregulated expression is involved in pathogenesis of parathyroid carcinomas. To clarify the roles of parafibromin expression in tumourigenesis and progression of gastric carcinomas, it was examined by immunohistochemistry (IHC) on tissue microarray containing gastric carcinomas (n = 508), adenomas (n = 45) and gastritis (n = 49) with a comparison of its expression with clinicopathological parametres of carcinomas. Gastric carcinoma cell lines (MKN28, AGS, MKN45, KATO-III and HGC-27) were studied for parafibromin expression by IHC and western blot. Parafibromin expression was localised in the nucleus of gastric epithelial cells, adenoma, carcinoma cells and cell lines. Its expression was gradually decreased from gastritis to gastric carcinoma, through gastric adenomas (p < 0.05) and inversely correlated with tumour size, depth of invasion, lymphatic invasion, lymph node metastasis and Union Internationale Contre le Cancer (UICC) staging (p < 0.05) but not with sex or venous invasion (p > 0.05). Parafibromin was strongly expressed in older carcinoma patients compared with younger ones (p < 0.05). There was stronger positivity of parafibromin in intestinal-type than diffuse-type carcinomas (p < 0.05). Univariate analysis indicated cumulative survival rate of patients with positive parafibromin expression to be higher than without its expression (p < 0.05). Multivariate analysis showed that age, tumour size, depth of invasion, lymphatic invasion, lymph node metastasis, UICC staging and Lauren’s classification but not sex, venous invasion or parafibromin expression were independent prognostic factors for carcinomas(p < 0.05). Downregulated parafibromin expression possibly contributed to pathogenesis, growth, invasion and metastasis of gastric carcinomas. It was considered as a promising marker to indicate the aggressive behaviours and prognosis of gastric carcinomas.     

Combined vindesine and razoxane shows antimetastatic activity in advanced soft tissue sarcomas

Background Razoxane and vindesine were shown to suppress distant metastasis in animal systems. Both drugs affect main steps of the metastatic cascade. Therefore, a pilot study was performed to study the influence of these drugs on the dynamics of metastasis in advanced soft tissue sarcomas (STS). This study was now updated. Methods Twenty-three patients with unresectable (n = 7) and oligometastatic STS (n = 16) received a basic treatment with razoxane and vindesine supported by radiotherapy and occasionally by surgery. Long-term treatment was intended in patients with metastatic disease. The cumulative number of new metastases after 6 and 9 months were determined. Thirty-six patients with comparable stages of STS treated with contemporary chemotherapy served as non-randomized, retrospective controls. The prognostic parameters of the groups were comparable. Results In patients receiving razoxane and vindesine, the median number of new metastases after 6 months was 0 (range, 0–40) and after 9 months likewise 0 (0–70). The corresponding numbers in the control group were 4.5 (range, 0–40) and 9 (0–>100) (P < 0.001). The progression-free survival at 6 months was 74% in the study group and 23% in the controls. The median survival time from the occurrence of the first metastasis or the time of unresectability was 20+ months (range, 8–120+) versus 9 months (range, 2–252) (P < 0.001). The combined treatment was associated with a low to moderate toxicity. Conclusions Trimodal treatment with razoxane, vindesine, and radiotherapy is feasible in patients with unresectable primaries and early metastatic STS. The combination inhibits the development of remote metastases in a majority of the patients and prolongs survival.     

Impact of tracheostomies on the long-term survival of patients with trisomy 13 syndrome

In this retrospective cohort study, we investigated the impact of tracheostomies on the long-term survival of children with trisomy 13 syndrome at a Japanese tertiary pediatric center. We compared survival and survival to discharge rates between patients who underwent tracheostomies during their NICU stays (T group, n = 8) and those who did not (non-T group, n = 11). A total of 19 patients enrolled. Median survival in all patients was 673 (266–1535) days. Significant differences in the 1-, 2-, and 3-year survival rates were found between the T and the non-T groups (100% vs. 46%, p = 0.018; 88% vs. 18%, p = 0.006; 63% vs. 9%, p = 0.041, respectively). The survival to discharge rate was higher in the T versus non-T group (75% vs. 45%, p = 0.352). This study highlights a significantly higher long-term survival of patients with trisomy 13 syndrome who underwent tracheostomies during their NICU stays.     

Impact of Switching Virologically Suppressed,HIV-1-Infected Patients from Twice-Daily Fixed-Dose Zidovudine/Lamivudine to Once-Daily Fixed-Dose Tenofovir Disoproxil Fumarate/Emtricitabine

Abstract

Objective: Evaluate the impact of switching from twice-daily zidovudine/lamivudine (AZT/3TC) to once-daily tenofovir DF plus emtricitabine (TDF/FTC) with efavirenz (EFV). Design: Prospective, multicenter, single-arm 24-week trial. Methods: Patients on EFV + AZT/3TC for =8 weeks with HIV-1 RNA <400 copies/mL were switched to EFV + TDF/FTC and assessed for safety/tolerability, virologic and immunologic responses, adherence, and quality of life at 4, 12, and 24 weeks. Results: Of 402 patients, 2% discontinued for an adverse event (AE) and 1 patient for virologic failure. At 24 weeks, 87% had HIV RNA <400 copies/mL, and 74% versus 71% at baseline had undetectable (HIV RNA <50 copies/mL) viral load (ITT; M=F). Treatment-emergent AEs were infrequent (≤5%) with gastrointestinal complaints being the most common. At 24 weeks compared to baseline, hemoglobin (Hb) increased by a median of 0.6 g/dL (p < .001), and a decrease in creatinine clearance of 7.6 mL/min (p < .001) was observed. Fasting lipids decreased slightly (p < .02) in a subset of patients studied (n = 160). A higher percentage of patients reported being “very satisfied” with treatment and the absence of regimen side effects at 24 weeks versus baseline (p < .001). At 24 weeks, 86% of patients took ≥95% of doses versus 78% at baseline (p = .002). Conclusion: Patients switched to EFV + TDF/FTC maintained virologic suppression and the regimen was well tolerated. Patients reported increased satisfaction with treatment and fewer were bothered by side effects.     

A Prognostic Biomarker for Gastric Cancer With Lymph Node Metastases

Gastric cancer is one of the leading causes of tumor‐related deaths in China. The tumor, node, metastasis (TNM) classification system is useful for predicting clinical prognosis of patients with gastric cancer. However, determining the presence of lymph node involvement in the early stages of gastric cancer is difficult without biopsy. Therefore, it is necessary to identify novel serum biomarkers for TNM cancer staging and prognostic follow‐up. In this study, we have reported fibrinopeptide‐A (FPA) with alanine truncation at the N‐terminal as a novel biomarker to differentiate gastric cancer with and without lymph node metastases. We analyzed 369 individual serum samples including gastric cancer patients without lymph node metastases (n = 33), gastric cancer patients with lymph node metastases (n = 157; confirmed by pathology), and age‐ and sex‐matched healthy individuals (n = 179). The data showed that 85.4% of patients with lymph node metastases were positive for FPA with alanine truncation at the N‐terminal (degAla‐FPA, 1,465.63 Da), as determined by tandem mass spectrometry (MS). Using degAla‐FPA as the biomarker, the sensitivity was 85.4% for gastric cancer patients with lymph node metastases, and the specificity was 100% for gastric cancer patients without lymph node metastases. The high sensitivity and specificity achieved with serum degAla‐FPA levels indicated that MS technology could facilitate the discovery of a novel and quantitative prognostic biomarker for gastric cancer with lymph node involvement. Anat Rec, 296:590–594, 2013. © 2013 Wiley Periodicals, Inc.     

Non‐invasive detection of glycine as a biomarker of malignancy in childhood brain tumours using in‐vivo 1H MRS at 1.5 Tesla confirmed by ex‐vivo high‐resolution magic‐angle spinning NMR

Management of brain tumours in children would benefit from improved non‐invasive diagnosis, characterisation and prognostic biomarkers. Metabolite profiles derived from in‐vivo MRS have been shown to provide such information. Studies indicate that using optimum a priori information on metabolite contents in the construction of linear combination (LC) models of MR spectra leads to improved metabolite profile estimation. Glycine (Gly) is usually neglected in such models due to strong overlap with myo‐inositol (mI) and a low concentration in normal brain. However, biological studies indicate that Gly is abundant in high‐grade brain tumours. This study aimed to investigate the quantitation of Gly in paediatric brain tumours using MRS analysed by LCModel?, and its potential as a non‐invasive biomarker of malignancy. Single‐voxel MRS was performed using PRESS (TR 1500 ms, TE 30 ms/135 ms) on a 1.5 T scanner. Forty‐seven cases (18 high grade (HG), 17 low grade (LG), 12 ungraded) were retrospectively selected if both short‐TE and long‐TE MRS (n = 33) or short‐TE MRS and high‐resolution magic‐angle spinning (HRMAS) of matched surgical samples (n = 15) were available. The inclusion of Gly in LCModel? analyses led to significantly reduced fit residues for both short‐TE and long‐TE MRS (p < 0.05). The Gly concentrations estimated from short‐TE MRS were significantly correlated with the long‐TE values (R = 0.91, p < 0.001). The Gly concentration estimated by LCModel? was significantly higher in HG versus LG tumours for both short‐TE (p < 1e‐6) and long‐TE (p = 0.003) MRS. This was consistent with the HRMAS results, which showed a significantly higher normalised Gly concentration in HG tumours (p < 0.05) and a significant correlation with the normalised Gly concentration measured from short‐TE in‐vivo MRS (p < 0.05). This study suggests that glycine can be reliably detected in paediatric brain tumours using in‐vivo MRS on standard clinical scanners and that it is a promising biomarker of tumour aggressiveness. Copyright © 2009 John Wiley & Sons, Ltd.