Anatomical basis of laparoscopic medial‐to‐lateral mobilization of the descending colon

In laparoscopic colorectal resection, the medial‐to‐lateral approach has been largely adopted. This approach can be initiated by the division of either the inferior mesenteric artery (IMA) or the inferior mesenteric vein (IMV). This cadaveric study aimed to establish the feasibility of IMV dissection as the initial landmark of medial‐to‐lateral left colonic mobilization for evaluating the size of the peritoneal window between the IMV at the lower part of the pancreas and the origin of the IMA (IMA‐IMV distance) and the point of origin of the IMA compared to the lower edge of the third part of the duodenum (IMA‐D3 distance). These distances were recorded on 30 fresh cadavers. The IMA‐D3 distance was 0.4 ± 2.2 cm (mean ± SD). The IMA originated from the aorta at the level of or below the D3 in 21 cases (70%). The IMA‐IMV distance was 5.5 ± 1.8 cm and was greater or equal to 5 cm (large window) in 21 cases (70%). IMA‐IMV distance was correlated with IMA‐D3 showing that a large window was inversely correlated with a low IMA origin (P < 0.001). IMA‐D3 distance was not correlated with weight, height and sex. IMA‐IMV distance was largerin male (6.7 ± 0.9 vs. 4.9 ± 1.8, P = 0.001) and correlated with weight, (r = 0.60, 95%CI = 0.03–0.10, P < 0.001) and height (r = 0.54, 95%CI = 0.05–0.21, P = 0.002). IMV can be used as the initial landmark for laparoscopic medial‐to‐lateral dissection in two‐thirds of cases. A too‐small window can require first IMA division. The choice between the two different medial‐to‐lateral approaches could be made by evaluating the anatomical relationship between IMA, IMV, and D3. Clin. Anat., 2013. © 2013 Wiley Periodicals, Inc.     

Evaluation of the serum levels of soluble IL‐2 receptor and endothelin‐1 in children with Crimean‐Congo hemorrhagic fever

We aimed to assess the association between serum levels of soluble IL‐2 receptor (sIL‐2r) and endothelin‐1 and severe infection in children with Crimean‐Congo hemorrhagic fever (CCHF). Fifty‐two patients under 18 years of age with a laboratory‐ confirmed diagnosis of CCHF and 38 healthy controls were enrolled in the study. Patients were classified into two groups based on disease severity (severe group and non‐severe group). The sIL‐2r and endothelin‐1 levels were observed to be significantly higher in patients with severe CCHF compared with those with non‐severe CCHF and the control group (p < 0.05). In addition, those with non‐severe CCHF were also found to have a significantly higher sIL‐2r level relative to the control group (p < 0.001). Although there was a positive correlation between sIL‐2r and endothelin‐1 levels, serum levels of both sIL‐2r and endothelin‐1 were negatively correlated with the platelets count. In children with CCHF, serum levels of sIL‐2r and endothelin‐1 were increased, and this increase is related to the severity of the disease. In this study, we concluded through prognosis that serum levels of sIL‐2r and endothelin‐1 might be related, and that hemophagocytic lymphohistiocytosis and endothelial injury might contribute to a pathogenesis of the disease.     

Proportion of goblet cell is associated with malignant potential in invasive mucinous adenocarcinoma of the lung

Invasive mucinous adenocarcinoma (IMA) is a newly classified variant of lung adenocarcinoma. The aim of this study was to examine the correlation between the proportion of goblet cells and the clinicopathological characteristics of IMA. Ninety‐nine patients with stage I IMA were included in this study. We estimated prognostic impact of goblet cell proportion. We classified them into two groups: the cases with a high goblet cell proportion (HGP, goblet cell proportion ≥80%) and the cases with a low goblet cell proportion (LGP, goblet cell proportion ≤30%), and compared the expression levels of five cancer progression markers and the number of tumor‐promoting stromal cells between the two groups. Univariate and multivariate analysis revealed that the goblet cell proportion was a prognostic factor for recurrence free survival (P < 0.01) and overall survival (P = 0.01). The expression levels of the cancer stem cell‐related marker, ALDH‐1, and proliferation‐related marker, geminin were significantly higher in the LGP group than in the HGP group. CD204+ tumor‐associated macrophages were significantly more in the LGP stroma than the HGP stroma. Our current study indicated that the proportion of goblet cells was correlated with the malignant potential in surgically resected IMA.     

Effect of TLR10 (2322A/G, 720A/C,and 992T/A) polymorphisms on the pathogenesis of Crimean Congo hemorrhagic fever disease

Crimean Congo hemorrhagic fever (CCHF) is a tick‐borne disease caused by the Crimean Congo hemorrhagic fever virus (CCHFV). Toll‐like receptors (TLRs) are type 1 transmembrane proteins of immune cells that play a critical role in innate and adaptive immunity. The present study first time aims to investigate the relation between TLR10 gene polymorphisms (720A/C, 992T/A, and 2322A/G), severity/non‐severity, fatality/non‐fatality, and CCFH disease by using PCR‐RFLP assay in a Turkish population. TLR10 720A/C polymorphism was determined to be statistically significant both genotype and allele frequency (P = 0,011, P = 0.015, respectively). TLR10 992T/A polymorphism was found statistically significant relationships between patient and control (P = 0.026) and individual with AA genotype have approximately three times greater risk than TT genotype (OR = 2.93). There was not a significant difference in 2322A/G genotype distribution (P = 0.152). There were also statistically significant associations between both TLR10 992T/A and 2322A/G polymorphism and patient mortality (P = 0.001 and P = 0.008, respectively). We have not found statistically any linkage among TLR10 haplotype, but individual AAA and GAT haplotype have higher risk than individual AAT haplotype (OR = 3.22, OR = 1.93, respectively). Consequently, this study shows that pathogenesis of CCHF disease is associated with the TLR10 720A/C and 992T/A polymorphisms. There is a statistically significant association in fatal/non‐fatal patients with TLR10 720A/C and 992T/A. The TLR10 992AA genotype might increase and TLR10 720CC genotype might decrease susceptibility to pathogenesis of CCHF disease. TLR 10 polymorphisms may be also an important biomarker for CCHF susceptibility and fatality rate.     

Prognostic relevance of miR‐124‐3p and its target TP53INP1 in pediatric ependymoma

Ependymoma is a malignant pediatric brain tumor, often incurable under the current treatment regimen. We aimed to evaluate the expression of microRNAs (miRs) in pediatric ependymoma tumors in an attempt to identify prognostic molecular markers which would lead to potential therapeutic targets. Following miR‐array expression analysis, we focused on 9 miRs that correlated with relapse which were further validated by quantitative real‐time PCR (qRT‐PCR) in a cohort of 67 patients. Western blotting and immunohistochemistry were used to measure target protein expression in 20 and 34 tumor samples, respectively. High expression of miR‐124‐3p significantly correlated with the lower progression‐free survival (PFS) of 16% compared to 67% in those expressing low levels (P = .002). Interestingly, in the group of patients with local disease (n = 56) expression levels of this miR distinguished 2 subgroups with a significantly different outcome (P = .001). miR‐124‐3p was identified as an independent prognostic factor of relapse in the multivariate analysis performed in the whole cohort and in the group with localized disease. In the localized group, a patient expressing high levels of miR‐124‐3p had a 4.1‐fold increased risk for relapse (P = .005). We demonstrated the direct binding of miR‐124‐3p to its target TP53INP1. Negative TP53INP1 protein levels correlated with a poor outcome (P = .034). We propose miR‐124‐3p and TP53INP1 as new biomarkers for prognostic stratification that may be possible therapeutic targets for ependymoma.     

Early use of tocilizumab in the prevention of adult respiratory failure in SARS‐CoV‐2 infections and the utilization of interleukin‐6 levels in the management

Respiratory failure in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection appears related to cytokine release syndrome that often results in mechanical ventilation (MV). We investigated the role of tocilizumab (TCZ) on interleukin‐6 (IL‐6) trends and MV in patients with SARS‐CoV‐2. In this longitudinal observational study, 112 patients were evaluated from 1 February to 31 May 2020. TCZ was administered followed by methylprednisolone to patients with >3L oxygen requirement and pneumonia severity index score ≤130 with computed tomography scan changes. IL‐6, C‐reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), D‐dimer, and procalcitonin were monitored on days 0, 3, and 6 of therapy. Statistical analyses were performed with significance ≤0.05. Eighty out of 112 SARS‐CoV‐2‐positive patients (45 males, 56.96%; 34 females, 43.04%) were included in this study. Seven patients expired (8.75%) and nine patients required MV (11.25%). Median IL‐6 levels pre‐administration of TCZ was 342.50 (78.25‐666.25) pg/mL compared with post‐administration on day 3 (563; 162‐783) pg/mL (P < .00001). On day 6, the median dropped to 545 (333.50‐678.50) pg/mL compared with day 3 (P = .709). CRP, ferritin, LDH, and D‐dimer levels were reduced after TCZ therapy. Early use of TCZ may reduce the need for MV and decrease CRP, ferritin, LDH, and D‐dimer levels. The sequential use of methylprednisolone for 72 hours seems to potentiate the effect and prolong the suppression of the cytokine storm. IL‐6 levels may be helpful as a prognostic tool.     

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.     

Evaluation of the association of serum levels of hyaluronic acid,sICAM-1, sVCAM-1, and VEGF-A with mortality and prognosis in patients with Crimean-Congo hemorrhagic fever

BackgroundCrimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral hemorrhagic disease. Pathogenesis of the disease has not been well described yet. A well-known pathogenic feature of CCHF virus is its capability to damage endothelium. Increased hyaluronic acid (HA) levels indicate liver sinusoidal endothelial damage. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and vascular endothelial growth factor-A (VEGF-A) play a role in the inflammatory process, vascular damage and plasma leakage.ObjectivesTo investigate whether or not there is a relationship between HA, sICAM-1, sVCAM-1 and VEGF-A serum levels and fatality in CCHF.Study designSixty-one patients who were confirmed by RT-PCR and serological tests for CCHF, included in the current study. HA, sICAM-1, sVCAM-1, VEGF-A levels in serum samples were analyzed by ELISA.ResultsThere were statistically significant differences between fatal and non-fatal CCHF patients in terms of HA, sICAM-1, sVCAM-1, and VEGF-A levels. In addition, AST and ALT levels were positively correlated with HA, sICAM-1, sVCAM-1, and VEGF-A levels.ConclusionHA, sICAM-1, sVCAM-1, and VEGF-A levels of the patients that died during hospitalization were statistically significantly higher than the patients that survived, and this finding suggests that the level of these molecules could be used as a prognostic marker in CCHF.     

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.     

Comparison of the diagnostic accuracy of thyroid fine‐needle aspiration in follicular‐patterned lesions using a 5‐tiered and a 6‐tiered diagnostic system: A double‐blind study of 140 cases with histological confirmation

Five‐tiered and 6‐tiered systems for reporting thyroid fine‐needle aspiration (FNA) results are used widely throughout the world. In this study, we present a double‐blind study of histologically confirmed follicular‐patterned neoplasms and evaluate the cytological classification of the same lesions according to both systems. One hundred and forty consecutive surgically resected thyroid follicular‐patterned lesions with a diagnostic preoperative FNA were retrieved from our archive. Two cytopathologists, who were blinded to all clinical information, classified each FNA case according to their respective routine diagnostic reporting system (5‐tiered or 6‐tiered). Interobserver variability was assessed using Cohen's Kappa (K) coefficient. Diagnostic accuracy was determined by measuring sensitivity and specificity. Receiver operator characteristic (ROC) curves were calculated for each cytopathologist. The 140 thyroid FNAs included histologically confirmed nodular hyperplasia, follicular adenomas, follicular carcinomas, and papillary carcinomas, follicular variant (35 cases for each) obtained from 104 females and 36 males with a mean age of 48.8 years and a mean tumor diameter of 27.8 mm. Negative predictive values (PV) for benign cases were 72.2% and 68.8% in the 5‐tiered and 6‐tiered systems, respectively (P = 0.7009). Positive PV were 100% for malignant cases in both systems. The sensitivity (78.6% vs. 72.9%, P = 0.4305), specificity (55.7% vs. 47.1%, P = 0.3103), and diagnostic accuracy (67.1% vs. 60.0%, P =0.2143) were similar between the systems. ROC curves almost entirely overlapped (P = 0.8937). Both the 5‐tiered and 6‐tiered systems show similar diagnostic accuracy in follicular‐patterned lesions, further supporting the adoption of a common reporting system for thyroid cytopathology. Diagn. Cytopathol. 2014;42:744–750. © 2014 Wiley Periodicals, Inc.     

Prognostic significance of immunophenotypes and a nodular pattern in primary mediastinal large B‐cell lymphoma

To investigate the clinicopathological and prognostic significance of a nodular pattern and immunophenotypes in primary mediastinal large B‐cell lymphoma (PMBL), histopathological features, including a nodular pattern and immunophenotypes, were analyzed in 58 Japanese PMBL patients. The patients were 23 men and 35 women with a median age of 31 years. The 4‐year progression free survival (PFS) rate was 78%, and the 4‐year overall survival (OS) rate was 89%. Among the histopathological and immunohistochemical features, Bcl6⁺ (P = 0.013), MUM1⁺ (P = 0.091), and pale cytoplasm (P = 0.064) were favorable prognostic indicators of PFS, and Bcl6⁺ (P = 0.051) and MUM1⁺ (P = 0.07) were favorable prognostic indicators of OS. Patients with Bcl2 negativity (n = 11) had 4‐year PFS and OS rates of 100%. Histologically, a nodular pattern, resembling nodular sclerosis classical Hodgkin lymphoma (CHL), was observed in 22 patients (38%). However, this was not a significant prognostic indicator. In conclusion, Bcl6⁺, MUM1⁺, Bcl2^‐, and pale cytoplasm are candidate favorable prognostic indicators for PMBL and should be further examined in larger studies. We suggest that PMBL with a nodular pattern may belong to the same histological spectrum as nodular sclerosis CHL.     

Association of MCP-1 promotor polymorphism with disease severity of Crimean-Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF) is a thick-borne viral zoonotic disease. The pathogenesis and the reasons why cases have a mild or severe course in CCHF have not yet been explained. In this study, we investigated the relationship between promoter -2518 A/G single-nucleotide polymorphism (SNP) of the MCP-1 gene and the clinical course of CCHF. The MCP-1-2518 A/G SNP (rs1024611) frequency was examined in 128 virologically/serologically confirmed CCHF patients and 181 healthy controls by using the PCR-RFLP method. When CCHF patients and controls were compared, no significant difference was found between genotype distributions and allele frequencies of the -2518 A/G SNP of MCP-1 gene (P > .05). Compared to the AA genotype, both AG (P = .016; OR = 2.57) and GG genotype (P = .039; OR = 3.43) were found with significantly higher frequencies in mild/moderate cases than in severe cases. Compared to the AG + GG genotype, AA showed a significant risk for severe CCHF (60.0% vs 38.4%, P = .02; OR = 2.41). In contrast, the AG genotype showed a significant protective effect against severe disease compared to AA + GG genotype (29.1% vs 47.9%, P = .013; OR = 2.58). Compared to mild/moderate cases, the A allele was found to be significantly higher in severe cases (0.745 vs 0.623, P = .039; OR = 1.77). However, no significant relationship was found between fatal and nonfatal cases in terms of genotype or allele frequencies (P > .05). In conclusion, both -2518 AA genotype and A allele of MCP-1 were associated with disease severity, and the AG genotype had a protective effect against a severe disease course in CCHF patients.     

Prognostic Evaluation of CapG,Gelsolin, P‐gp,GSTP1, and Topo‐II Proteins in Non‐Small Cell Lung Cancer

Metastasis and multidrug resistance (MDR) are the main reasons for the poor prognosis of non‐small cell lung cancer (NSCLC) patients. The use of biomarkers may contribute to a more accurate prediction of tumor metastasis, a better response to chemotherapy, and better patient survival. Gelsolin‐like actin‐capping protein (CapG) and gelsolin have been identified as playing important roles in tumor invasion and metastasis. Permeability glycoprotein (P‐gp), glutathione S‐transferase pi (GSTP1), and topoisomerase‐II (Topo‐II) are proteins that are closely related to MDR. In this study, we assessed the prognostic significance of CapG and gelsolin (both markers of tumor motility), and of P‐gp, GSTP1, and Topo‐II (markers of MDR) in NSCLC patients. One hundred and twenty‐one patients with pathologically confirmed, resectable NSCLC were included in the study. The expression levels of the five kinds of proteins mentioned above were determined by immunohistochemistry (IHC). The correlation between the clinical characteristics and IHC findings were analyzed. Expression of CapG, gelsolin, and P‐gp was found to be associated with an increased risk of death (Hazard Ratio (HR) = 2.799, 95% Confidence Interval (CI) = 1.2705–6.169, P = 0.011; HR = 3.968, 95% CI = 1.811–8.693, P = 0.001; HR = 3.251, 95% CI = 1.456–7.260, P = 0.004, respectively), whereas expression of GSTP1 and Topo‐II was not. These results suggest that higher tumor motility and MDR may be important in NSCLC prognosis. Anat Rec, 2012. © 2011 Wiley Periodicals, Inc.     

Prognostic significance of CD20 expression and Epstein‐Barr virus (EBV) association in classical Hodgkin lymphoma in Japan: A clinicopathologic study

To investigate the clinicopathological significance of CD20 expression and Epstein‐Barr virus (EBV) association in Hodgkin and Reed–Sterberg cells of classical Hodgkin lymphoma (CHL), CD20 expression and EBV positivity (by EBER in situ hybridization) were investigated in 389 CHL patients in Japan. They included 74 CD20‐positive cases (19%) and 315 CD20‐negative cases (81%). CD20‐positive cases showed significantly older age at onset (P = 0.018) and higher association with EBV (P = 0.002). Multivariate analysis identified EBV‐positivity (but not CD20‐positivity), presence of B symptoms, thrombocytopenia, elevated serum lactate dehydrogenase and performance status >1 as poor prognostic factors for overall survival (OS). We constructed a new prognostic model with these five factors classifying patients into three groups: low risk, 0–1 adverse factor; intermediate risk, 2–3 factors; high risk, 4–5 factors. This prognostic model could stratify the prognosis of CHL patients (P < 0.0001). For 144 patients (58%) classified into the low‐risk group, the 5‐year OS was 91%. For 92 patients (37%) in the intermediate group, the 5‐year OS was 66%; for 11 patients (5%) in the high‐risk group, the 5‐year OS was 36%. In conclusion, EBV is identified as an independent poor prognostic factor for CHL patients. Therefore, examination of EBV association in CHL is recommended as routine pathologic practice especially in countries where EBV infection prevails.     

Serum thrombin-activatable fibrinolysis inhibitor levels and its relation with pathogenesis and bleeding and prognosis in patients with Crimean Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF) is a viral hemorrhagic fever, which is common in Turkey and globally. The pathogenesis of coagulation disorders, which is seen in viral hemorrhagic fevers remains to be elucidated. Thrombin-activatable fibrinolysis inhibitor (TAFI) has a key role in this process In this study, we aimed to evaluate whether TAFI levels contributed to bleeding and whether it is related to prognosis in CCHF patients. Eighty-four patients older than 15 years of age, who were admitted to our hospital who had positive immunoglobulin M (enzyme-linked immunosorbent assay [ELISA]) and/or polymerase chain reaction test results for CCHF between 2009 and 2010, were included in the study. The control group included 30 healthy adults. The plasma TAFI levels were compared between patients and controls, and also between patients with bleeding and no bleeding, and between patients with mild-moderate and severe disease. The mean TAFI levels were lower in patients (mean: 87.82 ng/ml, median: 61.69 ng/ml (interquartile range [IQR] 30.49–537.95) than controls (mean: 313.5 ng/ml with a median: 338.5 ng/ml (IQR 182–418). However, median TAFI levels were significantly higher in patients with bleeding compared to those without bleeding (78.99 and 50.28 ng/ml, respectively; p = 0.032). Median IQR TAFI levels were similar between patients with mild-moderate and severe disease (64.72 (41.37–113.85), and, 58.66 (42.44–118.93) ng/ml, respectively; p = 0.09) and survivors and nonsurvivors (86.14 ± 77.98 and 103.48 ± 69.92, respectively; p = 0.3). Although TAFI levels were lower in the patients with CCHF compared to healthy controls, it does not seem to be a major player in the prognosis.     

Nm23‐H1 nuclear expression is associated with a more favourable prognosis in laryngeal carcinoma: univariate and multivariate analysis

Marioni G, Ottaviano G, Lionello M, Lora L, Lovato A, Staffieri C, Favaretto N, Giacomelli L, Stellini E, Staffieri A & Blandamura S
(2012) Histopathology
Nm23‐H1 nuclear expression is associated with a more favourable prognosis in laryngeal carcinoma: univariate and multivariate analysis Aims: To use image analysis and multivariate analysis to investigate the prognostic significance of Nm23‐H1 subcellular localization in a large cohort of laryngeal squamous cell carcinomas (LSCCs). Methods and results: Nm23‐H1 total and nuclear levels were immunohistochemically determined and calculated with an image analysis system in 104 consecutively operated LSCCs. The mean follow‐up was 58.3 ± 35.1 months (median 45 months). Total Nm23‐H1 levels correlated only with patient stratification by pT (P = 0.01). Mean nuclear Nm23‐H1 levels were lower in patients with recurrent disease (P = 0.01), and disease‐free survival (DFS) was longer in patients whose nuclear levels of Nm23‐H1 were >2.0% than in those with levels ≤2.0% (P = 0.019). On multivariate analysis, Nm23‐H1 nuclear expression [hazard ratio (HR) 2.59, P = 0.005] and N stage (HR 3.60, P = 0.0001) were prognostically significant in relation to DFS. Conclusions: In LSCC, Nm23‐H1 nuclear expression may be useful for identifying patients at higher risk of recurrence after treatment and who might be considered for more aggressive therapy. Further investigations are needed before Nm23‐H1 can be considered for use in targeted treatments for LSCC.     

Ischemia-modified albumin improves the usefulness of standard cardiac biomarkers for the diagnosis of myocardial ischemia in the emergency department setting

We studied the role of ischemia-modified albumin (IMA) with standard biomarkers (myoglobin, creatine kinase-MB [CK-MB], troponin I [TnI]) in assessment of 200 patients with suspected myocardial ischemia admitted to the emergency department. Every case was reviewed by a cardiologist. A clinical diagnosis of ischemia was assigned and correlated with biomarker test results. Of the patients, 25 (13.0%) had myocardial ischemia. Receiver operating characteristic curves demonstrated IMA as highly sensitive but somewhat poorly specific for the presence of ischemia (area under curve, 0.63; P = .01). With a cut point of 90 U/mL, the Albumin Cobalt Binding Test had 80% sensitivity and 31% specificity for diagnosing ischemia and a negative predictive value of 92%. IMA was positive in 4 of 5 patients with electrocardiographic (ECG) evidence of ischemia and 16 of 20 patients with coronary ischemia but negative ECG. Among the same patients, the myoglobin-CK-MB-TnI triad had a sensitivity of 57%. The combination of IMA-myoglobin-CK-MB-TnI increased the sensitivity for detecting ischemia to 97%, with a negative predictive value of 92%. IMA is highly sensitive and has a high negative predictive value, which might improve the usefulness of standard biomarkers of myocardial ischemia.     

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.     

The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever

BackgroundCrimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family. It has recently been reported that soluble urokinase-type plasminogen activator receptor (suPAR), secreted from endothelial cells and the mononuclear phagocyte system, one of the main targets of the CCHF virus, is a potential biomarker for several bacterial and viral infection diseases.ObjectivesThis study was intended to determine the diagnostic and prognostic significance of suPAR levels in CCHF.Study designThis retrospective study was conducted between June 2006 and August 2009 using plasma from patients monitored with a diagnosis of CCHF and from healthy blood donors. Levels of plasma suPAR were determined using an enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's instructions.ResultsOne hundred CCHF patients were enrolled in the study. The control group was made up of 53 healthy blood donors. suPAR values of 6.2 ± 4.2 were determined in the CCHF patients and of 2.3 ± 0.6 in the control group (p < 0.0001). A suPAR level optimum diagnostic cut-off point of 3.06 ng/mL was determined, with an area underneath the ROC (AUROC) curve of 0.94 (95% CI: 0.89–0.97), sensitivity of 87% (95% CI: 79–93%), specificity of 92% (95% CI: 82–98%), PPV of 95% and NPV of 79%. Five of the patients died. suPAR was 18.4 ± 9.1 in the patients that died and 5.6 ± 2.6 in the survivors (p = 0.034). In terms of mortality, suPAR level had an optimum diagnostic cut-off point of 10.6 ng/mL, AUROC of 0.97 (95% CI: 0.94–0.99), sensitivity of 100% (95% CI: 48–100%), specificity of 96% (95% CI: 90–99%), PPV of 50% and NPV of 100%.ConclusionsPlasma suPAR level, a new biomarker, is a test that can be used in the differential diagnosis and monitoring of CCHF in patients admitted to hospital with suspected infection. The test is at the same time important in being a possible predictor of mortality.