High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16-23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrollment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy = 100%; 95% CI:12-100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.     

Inguinal hernia orifice for specimen extraction after laparoscopic resections

Specimen extraction is an unavoidable step in all laparoscopic resections. To this day there is no standardized retrieval incision for each procedure and the choice is made individually, yet based on the surgeon's experience and preference. Additionally, worldwide prevalence of inguinal hernia is high and many patients with this condition require surgical intervention for a distinct reason. In these particular cases, the hernia orifice can be seeing as an opportunity, allowing specimen retrieval when an open repair is performed immediately after the laparoscopic resection. In the present article, the authors propose this new option. Three patients who underwent this technique are also presented. Discussion is focused on the advantages and critics of the approach.     

Intrahepatic Lymphatic Invasion but not Vascular Invasion is a Major Prognostic Factor after Resection of Colorectal Cancer Liver Metastases

Background

Despite advances in diagnosis and surgical strategies, up to 70 % of patients will develop recurrence of the disease after resection of colorectal cancer liver metastases (CRCLM). The purpose of our study was to determine the frequency of four different mechanisms of intrahepatic dissemination, and to evaluate the impact of each mechanism on patient outcomes.

Methods

The medical records of 118 patients who underwent a first resection of CRCLM during the period between 2000 and 2010 were reviewed. Clinicopathologic variables and outcome parameters were examined. Resected specimens were submitted to routine histological evaluation, and immunohistochemical staining with D2-40 (lymphatic vessels), CD34 (blood vessels), CK-7 (biliary epithelium), and CK-20 (CRC cells).

Results

The mean follow-up after resection was 38 months. Tumor recurrence was observed in 76 patients, with a median interval of 13 months after resection. Overall survival and disease-free survival (DFS) rates after hepatectomy were 62 and 56 %, and 26 and 24 % at 3 and 5 years, respectively. Intrahepatic microscopic invasion included portal venous in 49 patients, sinusoidal in 43 patients, biliary in 20 patients, and lymphatic in 33 patients. Intra-hepatic lymphatic invasion was the only mechanism of dissemination independently associated with the risk of hepatic recurrence (odds ratio 2.75) and shorter DFS (p = 0.006).

Conclusion

Intrahepatic lymphatic invasion is a significant prognostic factor. Other mechanisms of invasion, although frequently observed, are not related to recurrence or survival, suggesting that the lymphatic system is the main route for dissemination of CRCLM. Furthermore, immunohistochemical detection of intrahepatic lymphatic invasion might be of value in clinical practice.     

Overview of safety experience with caspofungin in clinical trials conducted over the first 15 years: a brief report

Safety experience is available from 32 completed clinical studies (17 Phase I and 15 Phase II–III) of caspofungin (CAS) conducted between 1995 and 2010 in adult and paediatric patients. Clinical and laboratory adverse events (AEs) were collected from all enrolled subjects and patients. Investigators identified the seriousness, causality and result of all AEs noted during study therapy and for up to 28 days post therapy. Up to 31 December 2010, full safety data are available from 1951 individuals who have received at least one dose of CAS in Phase I–III clinical studies, including 171 paediatric patients, 394 volunteer adult subjects and 1386 adult patients (276 with oropharyngeal/oesophageal candidiasis, 366 with invasive candidiasis, 180 with invasive aspergillosis and 564 with persistent fever and neutropenia). CAS was administered for up to 196 days at daily doses ranging from 5 mg to 210 mg. Overall, 41.8% of CAS recipients had an AE that was classified as drug-related. The most frequently reported drug-related AEs were fever (9.3%), chills (5.2%), increased alanine aminotransferase (6.5%), increased aspartate aminotransferase (6.0%) and increased alkaline phosphatase (5.2%). Serious AEs were reported in 27.3% of CAS recipients overall but were attributed to CAS in only 0.8%, and discontinuation of CAS due to a drug-related AE was infrequent (2.7%). Dose-related CAS toxicity was not observed. In conclusion, CAS has demonstrated a favourable safety profile in 1951 adult and paediatric patients enrolled in clinical trials.