Three hundred patients were enrolled in a double-blind, randomized, controlled study designed to investigate the ability of supplemental perioperative oxygen to reduce wound infection. Participants were age 18 to 80 years, had no coexisting serious medical conditions, and were scheduled to undergo elective colorectal surgery at one of 14 participating hospitals in Spain. No patients undergoing minor or laparoscopic surgery were included. Anesthesia and antibiotic prophylaxis were standardized for the study. Patients were randomized by computer-generated codes to receive an oxygen/air mixture of 30% or 80% fraction of inspired oxygen (F10 2 ) intraoperatively and postoperatively for 6 hours. After 6 hours, oxygen was given only in amounts needed to maintain 92% saturation. Postoperative care was determined by the attending surgeon who was unaware of the patient's oxygen group.Wounds were inspected daily and surgical site infections (SSI) were diagnosed according to the definitions of the Centers for Disease Control and Prevention. Infections occurring during the first 14 days were considered for analysis.Nine patients did not meet inclusion criteria. Of the remaining 291 patients, 143 received 30% and 148 received 80% oxygen. The 2 groups were similar in clinical characteristics, including preoperative laboratory studies and risk of infection score. Surgical characteristics, including length of operative procedure, blood loss, and transfusion rate, were also similar between the 2 groups.Fifty-seven patients (19.3%) developed a wound infection. The incidence of wound infection was 35 of 143 (24%) in the 30% F10 2 group and 22 of 148 (14.9%) in the 80% F10 2 patients (P ϭ 0.04). The risk of SSI was 39% lower in the high oxygen group compared with those who received less oxygen (relative risk, 0.61; 95% confidence interval [CI], 0.38-0.98). Other measures of surgical outcome, including return of bowel function, ability to tolerate solid food, ambulation, suture removal, and duration of hospitalization, were not significantly different for the 2 treatment groups. When patients who developed wound infections were compared with those without infection, the group with SSI had a longer time to ambulation (mean, 4.9 vs 3.9 days; P ϭ 0.008), a longer time to staple removal (11.6 vs 10.1 days; P ϭ 0.007), and were in the hospital longer (15.1 vs 10.7 days; P ϭ 0.001).Two patients, both in the 30% oxygen group, died of sepsis during the study period. After multivariate analysis of possible confounding variables, the relative risk of wound infection in patients who received 80% oxygen was 0.46 (95% CI, 0.22-0.95; P ϭ 0.04) compared with those who received 30% oxygen. EDITORIAL COMMENT(In the United States these days, surgical wound infection occurs after less than 1% of abdominal or vaginal hysterectomies. This is a marked reduction in the last 20 years brought about largely because of prophylactic antibiotics. More than 25 prospective, randomized studies have shown the effectiveness of prophylactic antibiotics in reducing pos...

Purpose: A better understanding of the molecular pathways underlying the development of epithelial ovarian cancer (EOC) is critical to identify ovarian tumor markers for use in diagnostic or therapeutic applications. The aims of this study were to integrate the results from 14 transcript profiling studies of EOC to identify novel biomarkers and to examine their expression in early and late stages of the disease.Experimental Design: A database incorporating genes identified as being highly up-regulated in each study was constructed. Candidate tumor markers were selected from genes that overlapped between studies and by evidence of surface membrane or secreted expression. The expression patterns of three integral membrane proteins, discoidin domain receptor 1 (DDR1), claudin 3 (CLDN3), and epithelial cell adhesion molecule, all of which are involved in cell adhesion, were evaluated in a cohort of 158 primary EOC using immunohistochemistry.Results: We confirmed that these genes are highly overexpressed in all histological subtypes of EOC compared with normal ovarian surface epithelium, identifying DDR1 and CLDN3 as new biomarkers of EOC. Furthermore, we determined that these genes are also expressed in ovarian epithelial inclusion cysts, a site of metaplastic changes within the normal ovary, in borderline tumors and in low-grade and stage cancer. A trend toward an association between low CLDN3 expression and poor patient outcome was also observed.Conclusions: These results suggest that up-regulation of DDR1, CLDN3, and epithelial cell adhesion molecule are early events in the development of EOC and have potential application in the early detection of disease.

Objective The aim of the study was to describe the features required for diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM). Materials and Methods The International Society of the Study of Vulvovaginal Diseases tasked the difficult pathologic diagnoses committee to develop consensus recommendations for clinicopathologic diagnosis of vulvar lichen planus, lichen sclerosus, and dVIN. The dVIN subgroup reviewed the literature and formulated diagnostic criteria that were reviewed by the committee and then approved by the International Society of the Study of Vulvovaginal Diseases membership. Results Differentiated vulvar intraepithelial neoplasia is the immediate precursor of human papillomavirus (HPV)–independent vulvar squamous cell carcinoma and shows a spectrum of clinical and microscopic appearances, some overlapping with HPV-related neoplasia. The histopathologic definition of dVIN is basal atypia combined with negative or nonblock-positive p16 and basal overexpressed, aberrant negative, or wild-type p53. The most common pattern of dVIN is keratinizing with acanthosis, aberrant rete ridge pattern, and premature maturation. The morphologic spectrum of keratinizing dVIN includes hypertrophic, atrophic, acantholytic, and subtle forms. A few dVIN cases are nonkeratinizing, with basaloid cells replacing more than 60% of epithelium. Vulvar aberrant maturation is an umbrella term for lesions with aberrant maturation that arise out of lichenoid dermatitis and lack the basal atypia required for dVIN. Conclusions Evaluation of women at risk for dVIN and VAM requires a collaborative approach by clinicians and pathologists experienced in vulvar disorders. Close surveillance of women with lichen sclerosus and use of these recommendations may assist in prevention of HPV-independent squamous cell carcinoma through detection and treatment of dVIN and VAM.

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Mucinous epithelial ovarian cancers (MOC) are clinically and morphologically distinct from the other histological subtypes of ovarian cancer. To determine the genetic basis of MOC and to identify potential tumour markers, gene expression profiling of 49 primary ovarian cancers of different histological subtypes was performed using a customised oligonucleotide microarray containing 459 000 probesets. The results show that MOC express a genetic profile that both differs and overlaps with other subtypes of epithelial ovarian cancer. Concordant with its histological phenotype, MOC express genes characteristic of mucinous carcinomas of varying epithelial origin, including intestinal carcinomas. Differences in gene expression between MOC and other histological subtypes of ovarian cancer were confirmed by RT -PCR and/or immunohistochemistry. In particular, galectin 4 (LGALS4) was highly and specifically expressed in MOC, but expressed at lower levels in benign mucinous cysts and borderline (atypical proliferative) tumours, supporting a malignant progression model of MOC. Hence LGALS4 may have application as an early and differential diagnostic marker of MOC.

Australia has implemented a high-coverage HPV vaccination program but has not, to date, established the distribution of HPV types that occur in cervical cancers in Australia. This information is important for determining the potential for cervical cancer prevention with both current and broader spectrum HPV vaccines. We analysed 847 cervical cancers diagnosed 2005 to 2015 in tertiary centres in the three most populous Australian states with resolution of specimens containing multiple HPV types using laser-capture microdissection. Archived FFPE tissue was reviewed by specialist pathologists, sandwich sectioned, and initially whole-tissue sections genotyped for HPV. Samples were first genotyped using SPF10-LiPA25 (version 1). Negative samples were screened with DNA ELISA kit HPV SPF10, followed by genotyping with SPF+ LiPA if ELISA positive. If still negative, samples were tested on a qPCR assay targeting the E6 region of HPV16, 18, 45 and 33. Of the 847 cancers (65.1% squamous, 28.7% adenocarcinoma, 4.3% adenosquamous, 2.0% other), 92.9% had HPV detected. Of the HPV-positive cancers, 607 of 787 (77.1%) contained HPV16 or 18, 125 of 787 (15.9%) contained HPV31/33/45/52 or 58, and 55 (7.0%) another HPV type. There was a strong correlation between HPV type and age, with younger women most likely to have HPV16/18 detected and least likely HPV negative. Our findings indicate that cervical cancers diagnosed in Australia more frequently contain HPV16/18 than in international series. This could be due to cervical screening in Australia increasing the proportion of adenocarcinomas, in which types 18 and 16 more strongly predominate, due to prevention of squamous cancers.

Summary Genetic changes orchestrated by human papillomaviruses are the most important known factors in carcinogenesis of the uterine cervix. However, it is clear that additional genetic events are necessary for tumour progression. We have used comparative genomic hybridization to document non-random chromosomal gains and losses within a subset of 37 cervical carcinomas matched for clinical stage Ib, but with different lymph node status. There were significantly more chromosomal changes in the primary tumours when the lymph nodes were positive for metastases. The most frequent copy number alterations were loss of 3p, 11q, 6q and 10q and gain of 3q. The smallest areas of loss and gain on chromosome 3 were 3p14-22 and 3q24-26. The study identifies progressive DNA copy number changes associated with early-stage invasive cervical cancers with and without lymph node metastases, a factor of potential prognostic and therapeutic value.