How best to interpret mixed human papillomavirus genotypes in high-grade cervical intraepithelial neoplasia lesions

Objectives

This study aimed to determine human papillomavirus (HPV) genotypes present in biopsy sections from young women of vaccine eligible age living in Victoria, Australia, with confirmed cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS) using laser capture microdissection (LCM).

Methods

Histologically confirmed CIN3 or AIS positive biopsies from vaccine eligible women (born after 30th June 1981, n = 169), between May 2011 and March 2013, were identified. CIN3 or AIS lesions were isolated from biopsy material using LCM, and the HPV genotypes present in whole tissue sections (WTS) as well as LCM-isolated lesion tissue were determined by a sensitive reverse hybridisation assay; RHA kit HPV SPF10-LiPA25, version 1 (Labo Bio-medical Products, Rijswijk, The Netherlands).

Results

One hundred and sixty-eight cases were shown to be HPV positive (99%), of which 20 (12%) had more than one HPV genotype detected using WTS-PCR. Evaluation by LCM of individual biopsies with mixed infections showed 18 cases (90%) had only one HPV genotype associated with each CIN3 lesion. HPV 16 was the most common HPV type, found in 95/168 cases (57%).

Conclusion

LCM-PCR allowed us to confirm the presence of a single HPV genotype associated with each biologically separate CIN3 lesion, supporting the theory that only one virus type causes each independent CIN lesion. LCM will provide an important tool in assessing vaccine effectiveness in HPV vaccine programs.     

Health-related quality of life following radical prostatectomy: long-term outcomes

Purpose

To identify the health-related quality of life (HRQoL) domains that radical prostatectomy (RP) impacts most negatively and to define the recovery of these domains over 30 months of observation.

Patients and methods

A total of 1,200 RP patients completed the Patient-Oriented Prostate Utility Scale-Psychometric (PORPUS-P; range 0–100, higher is better), a prostate cancer-specific HRQoL measure, prior to RP and at 0–3 (T1), 3–9 (T2), 9–18 (T3) and 18–30 (T4) months post-RP. HRQoL changes were examined using paired t tests and a mixed-effect growth curve model. Multivariable analyses were performed to investigate demographic and treatment factors predicting the change in HRQoL.

Results

Mean baseline PORPUS-P score, 83.1, fell to 66.5 (p < 0.001) at T1. Over time HRQoL improved but did not return to baseline (T4 mean 76.4, p < 0.001). Domain analysis revealed that sexual function (p < 0.001), sexual drive (p < 0.001), energy (p = 0.001) and bladder control (p < 0.001) failed to return to baseline at T4. Sexual function demonstrated the greatest impairment overall. The multivariable model revealed Black men experienced greater losses in global HRQoL compared with White men (coefficient ?2.77, 95 % CI ?5.00 to ?0.54, p = 0.015). High baseline HRQoL, pro-erectile aid use and bilateral nerve-sparing were significantly associated with smaller reductions in HRQoL post-RP.

Conclusion

Overall HRQoL, sexual drive, sexual function, energy and bladder control do not return to preoperative levels within 30 months post-RP. Black patients experience the greatest reductions in HRQoL. HRQoL losses may be ameliorated by use of pro-erectile aids. These findings help to identify at-risk patient populations and inform survivorship programs.     

Limited correlation between systemic biomarkers and neurocognitive performance before and during HIV treatment

The AIDS Clinical Trials Group (ACTG) study A5303 investigated the associations between neuropsychological performance (NP) and inflammatory biomarkers in HIV-infected participants. Fifteen NP tests were administered at baseline and week 48 to 233 ART naïve participants randomized to maraviroc- or tenofovir-containing ART. Neurocognition correlated modestly with markers of lymphocyte activation and inflammation pre-ART (percent CD38+/HLA-DR+(CD4+) (r = − 0.22, p = 0.02) and percent CD38+/HLA-DR+(CD8+) (r = − 0.25, p = 0.02)), and with some monocyte subsets during ART (r = 0.25, p = 0.02). Higher interleukin-6 and percent CD38+/HLA-DR+(CD8+) were independently associated with worse severity of HIV-associated neurocognitive disorders (HAND) (p = 0.04 and 0.01, respectively). More studies to identify HAND biomarkers are needed.     

Community-based situation analysis of maternal and neonatal care in South Africa to explore factors that impact utilization of maternal health services

This community situational analysis determined factors impacting the utilization of maternal health services in South Africa. Quantitative and qualitative research methods were used, including semistructured household interviews, case studies of women with no antenatal care and/or home birth, and verbal/social autopsies of maternal and infant deaths, conducted in three diverse sites across the country. Data analysis used quantitative statistics for the semistructured interviews and a qualitative thematic content approach for the case studies and verbal/social autopsies. Each component was analyzed separately and then triangulated. The following themes emerged: 1) transport and distance to care were the biggest problems, particularly in rural areas; 2) providers' communication with families was very poor; 3) health-seeking behavior was better than anticipated; 4) treatment by health providers and quality of care showed mixed results; 5) HIV/AIDS is a major issue; however, basic maternity and neonatal service quality cannot be overlooked; and 6) families and communities are an untapped resource for improving maternal and neonatal health. Implications for maternal and infant health care in developing countries are discussed, with a particular focus on barriers to utilization and involvement of communities and families in maternity care.     

George Peters Award: How does breast-specific gamma imaging affect the management of patients with newly diagnosed breast cancer?

Background

We sought to determine the number of patients with known breast cancer who were found to have an additional, mammographically occult lesion detected on breast-specific gamma imaging (BSGI).

Methods

An institutional review board-approved review of all patients who underwent BSGI at Beth Israel Medical Center from 2006 to 2008 was performed.

Results

A total of 82 patients underwent BSGI for newly diagnosed breast cancer. Of these, 18 had an additional abnormality, and 17 were biopsied. There were 4 cases of invasive ductal carcinoma, 1 invasive lobular carcinoma, 1 ductal carcinoma in situ, 1 lobular carcinoma in situ, 2 papillomas, and 8 benign biopsies. One patient proceeded directly to mastectomy and an area of ductal carcinoma in situ was found, corresponding to the BSGI.

Conclusions

In our study group, 22% of patients had a surgical change in management based on BSGI findings. BSGI detected additional carcinoma in 9%. BSGI plays an important role in the clinical management of patients with known breast cancer.     

Distal Pancreatectomy with En Bloc Celiac Axis Resection for Locally Advanced Pancreatic Adenocarcinoma Following Neoadjuvant Therapy

Background

Celiac trunk encasement by adenocarcinoma of the pancreatic body is generally regarded as a contraindication for surgical resection. Recent studies have suggested that a subset of stage III patients will succumb to their disease in the absence of distant metastases. We hypothesized that patients with stage III tumors invading the celiac trunk, who are free of distant disease following neoadjuvant therapy, may derive prolonged survival benefit from aggressive surgical resection.

Methods

We performed a retrospective review of distal pancreatectomies with en bloc celiac axis resection for pancreatic adenocarcinoma.

Results

Eleven patients underwent a distal pancreatectomy with en bloc celiac axis resection after completing neoadjuvant chemoradiation therapy. Median operative time was 8?h, 14?min, and median estimated blood loss was 700?ml. Median length of stay was 9?days. Five patients (45%) had postoperative complications; three were Clavien grade I. Four patients (35%) had pancreatic leaks; two were ISGPF grade B, and two were grade A. There were two 90-day perioperative deaths. Ten patients had R0 resections (91%). After a median follow-up of 41?weeks, six patients recurred. Four of the five patients with SMAD4 loss recurred, and two of the five patients with intact SMAD4 recurred. Median disease-free and overall survival were 21?weeks and 26?months, respectively.

Conclusions

Resection of pancreatic body adenocarcinoma with celiac axis resection is technically feasible with acceptable perioperative morbidity and mortality.