Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis

Objective

We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3).

Methods

Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013.

Results

The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001).

Conclusion

Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.     

Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide

We previously evaluated Wilms’ tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA‐A*24:02 restricted, 9‐mer WT1‐235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1‐235‐specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1‐235 peptide (WT1‐235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine. The WT1‐235 IgG antibody, which was undetectable before vaccination, became detectable in 30 (50.8%) of a total of 59 patients during 3 months of WT1 peptide vaccination. The dominant WT1‐235 IgG antibody subclass was Th1‐type, IgG₁ and IgG₃. WT1‐235 IgG antibody production was significantly and positively correlated with both progression‐free survival (PFS) and overall survival (OS). Importantly, the combination of WT1‐235 IgG antibody production and positive delayed type‐hypersensitivity (DTH) to the WT1‐235 peptide was a better prognostic marker for long‐term OS than either parameter alone. These results suggested that WT1‐235 peptide vaccination induces not only WT1‐235‐specific CTLs as previously described but also WT1‐235‐specific humoral immune responses associated with antitumor cellular immune response. Our results indicate that the WT1 IgG antibody against the WT1 peptide may be a useful predictive marker, with better predictive performance in combination with DTH to WT1 peptide, and provide a new insight into the antitumor immune response induction in WT1 peptide vaccine‐treated patients.     

A retrospective analysis on the utility and complications of upper arm ports in 433 cases at a single institute

Background

We have employed upper arm central venous ports (UACVPs) since 2006 for long-term intravenous chemotherapy (CTx) or fluid supplementation. We evaluated the long-term availability of CVPs implanted in the upper arm to determine whether UACVPs could be one of the treatment options besides chest CVPs in terms of CVP-related complications.

Methods

We reviewed the medical records of all patients who underwent subcutaneous implantation of UACVPs at Kyoto University Hospital from 1 April, 2006 to 30 June, 2009. We assessed the indwelling duration of the UACVPs and the incidences of early and late UACVP-related complications.

Results

A total of 433 patients underwent subcutaneous implantation of UACVPs during this time period. The cumulative follow-up period was 251,538 catheter days, and the median duration of UACVP indwelling was 439.0 days (1–2, 24). There was no UACVP-related mortality throughout the study period. A total of 83 UACVP-related complications occurred (19.2 %), including 43 cases of infection (9.9 %, 0.17/1000 catheter days), ten cases of catheter-related thrombosis (2.3 %, 0.040/1000 catheter days), ten cases of occlusion (2.3 %, 0.040/1000 catheter days), nine cases of catheter dislocation (2.0 %, 0.036/1000 catheter days), five cases of port leakage (1.2 %, 0.019/1000 catheter days), four cases of skin dehiscence (0.9 %, 0.015/1000 catheter days) and two cases of port chamber twist (0.5 %, 0.008/1000 catheter days). The removal-free one-year port availability was estimated at 87.8 %.

Conclusions

UACVPs were of long-term utility, with complication rates comparable to those of chest CVPs previously reported.

     

Expression of the anaphylatoxin C5a receptor in gastric cancer: implications for vascular invasion and patient outcomes

The C5a receptor (C5aR) expressed in various types of cancers is involved in C5a-induced cancer cell invasion. However, its role in gastric cancer has not yet been fully elucidated. Therefore, we studied the clinical significance of C5aR expression in gastric cancer. The association of C5aR expression in gastric cancer, determined by immunostaining using the anti-C5aR antibody, with clinicopathological parameters and outcomes was evaluated in 148 patients. Further, the association of C5aR expression in liver metastatic sites with clinicopathological parameters was investigated in a separate cohort of 58 patients who underwent hepatectomy. High tumoral C5aR expression (n = 45, 30.4 %) was significantly related to tumor location, cancer invasion depth, vascular and lymphatic invasion, and tumor stage. The 5-year recurrence-free and overall survival rates of patients with high tumoral C5aR expression were significantly lower than those of patients with low tumoral C5aR expression (50.9 vs. 84.2 %, P = 0.002 and 58.8 vs. 86.1 %, P = 0.007, respectively). The incidence of liver metastasis was significantly higher in patients with high tumoral C5aR expression (13.3 %) than in those with low tumoral C5aR expression (3.9 %; P = 0.04). C5aR expression at liver metastatic sites was associated with the C5aR expression status at the primary site (P = 0.0004), vascular invasion at the primary site (P = 0.04), and tumor size at the metastatic site (P = 0.01). C5aR expression in gastric cancer was associated with cancer progression, liver metastasis, and poor prognosis. Therefore, C5aR may represent a prognostic factor and therapeutic target in gastric cancer.     

Clinicopathological features of gastric cancer in young patients

Background

Early-onset gastric cancer is relatively rare. To evaluate the clinicopathological features and surgical outcome of young patients with gastric cancer, this retrospective comparative study was conducted.

Methods

From 2000 to 2010, 4882 patients underwent surgery for gastric adenocarcinoma in our institution. A total of 136 patients under 40 years old were enrolled as the young group, and a total of 1435 patients aged between 60 and 69 were identified as the control group for this study. The patient’s characteristics, pathological findings, surgical and clinical outcomes were reviewed, and the risk factors of recurrence were compared between the two groups.

Results

Among the young group, patients had significantly fewer comorbidities and postoperative complications. The patient proportion having 7 or more lymph node metastases was higher in the young group (25 %) than in the control group (16 %). The presence of lymph node metastasis was identified as a strong risk factor for recurrence (odds ratio = 4.31) in the young group according to the results of the step-wise logistic regression analysis. Although the disease-specific survival at stage II was relatively better in the young group (p = 0.0439) than in the control group, there were no significant differences in overall survival for all stages.

Conclusion

Early-onset gastric cancer is likely to present lymph node metastases. The survival rate of gastric cancer in young patients was equivalent to that in patients in their 60s, which is the typical age at onset.

     

Detection of HBV core promoter and precore mutations helps distinguish flares of chronic hepatitis from acute hepatitis B

Background and Aim: Acute exacerbation of chronic hepatitis B has to be distinguished from acute hepatitis, because treatment strategies differ between them. Methods: Mutations in the core promoter and precore region of hepatitis B virus (HBV) were determined in 36 patients with acute exacerbation of chronic hepatitis B, in whom alanine aminotransferase (ALT) increased above 500 IU/L, as well as the 36 patients with acute hepatitis. Results: Mutations in the core promoter (A1762T/G1764A) and precore region (G1896A) were more frequent in patients with acute exacerbation of chronic hepatitis than acute hepatitis (81% vs 19%; P < 0.0001 and 58% vs 6%; P < 0.0001, respectively). Of the 19 patients with mutations in both the core promoter and precore region, 17 (89%) had acute exacerbation of chronic hepatitis. In contrast, among the 32 patients with the wild‐type for both the core promoter and precore region, 29 (89%) developed acute hepatitis. By multivariate analysis, the double mutation in the core promoter was predictive of acute exacerbation in chronic hepatitis with the highest odds ratio at 26.4. Conclusions: In patients with hepatitis B having ALT levels >500 IU/L, mutations in the core promoter and precore region are useful in distinguishing acute exacerbation of chronic from acute HBV infection. Detection of these mutations would be useful for commencing prompt antiviral treatments on patients with acute exacerbation of chronic hepatitis for a better prognosis.     

Impact of obesity on the surgical outcome following repeat hepatic resection in Japanese patients with recurrent hepatocellular carcinoma

AIM： To evaluate the impact of obesity on the postoperative outcome after hepatic resection in patients with hepatocellular carcinoma （HCC）. METHODS： Data from 328 consecutive patients with primary HCC and 60 patients with recurrent HCC were studied. We compared the surgical outcomes between the non-obese group （body mass index： BMI 〈 25 kg/m2） and the obese group （BMI ≥ 25 kg/m2）. RESULTS： Following curative hepatectomy in patients with primary HCC, the incidence of postoperative complications and the long-term prognosis in the nonobese group （n = 240） were comparable to those in the obese group （n = 88）. Among patients with recurrent HCC, the incidence of postoperative complications after repeat hepatectomy was not significantly different between the non-obese group （n = 44） and the obese group （n = 16）. However, patients in the obese group showed a significantly poorer long-term prognosis than those in the non-obese group （P 〈 0.05, five-yearsurvival rate; 51.9% and 92.0%, respectively）. CONCLUSION： Obesity alone may not have an adverse effect on the surgical outcomes of patients with primary HCC. However, greater caution seems to be required when planning a repeat hepatectomy for obese patients with recurrent HCC.