Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection.

Eight weeks duration of ledipasvir/sofosbuvir (LDV/SOF) can be considered in genotype 1 hepatitis C virus-infected patients who are treatment-naive, do not have cirrhosis, and have a pretreatment viral load <6,000,000 IU/mL. The effectiveness of this regimen, however, has not been fully confirmed by real-world experience. Using data from real-world cohorts, we aimed to determine the effectiveness of 8 weeks of LDV/SOF treatment, examine variables associated with relapse after treatment with this regimen, and compare the effectiveness of 8 weeks and 12 weeks of LDV/SOF treatment. To evaluate the effectiveness of 8 weeks of therapy and characteristics associated with relapse, we used individual patient data from the IFI (Institut für Interdisziplinäre Medizin), Burman's Pharmacy, and Kaiser Permanente Southern California. All patients had fibrosis staging assessed with biopsy, transient elastography, or serum biomarkers. We also performed a systematic review and meta-analysis of six additional real-world cohorts, to compare effectiveness of 8 weeks to 12 weeks duration. In our pooled data analysis, 634 patients were treated for 8 weeks with LDV/SOF, of whom all had outcomes of cure or relapse without loss to follow-up. Per protocol rates of sustained virologic response at 12 weeks were 98.1% (622/634) in the full cohort and 97.9% (571/583) among treatment-eligible patients. Exact logistic regression revealed no specific patient characteristics associated with relapse. Our meta-analysis of six additional real-world cohorts, comprised of 5,637 patients, demonstrated similar risk for relapse between 8 weeks and 12 weeks of LDV/SOF (relative risk = 0.99, 95% confidence interval 0.98-1.00). CONCLUSION: An 8-week duration of treatment with LDV/SOF is highly effective in properly selected patients; greater use of this regimen is recommended. (Hepatology 2017;65:1094-1103).

Evaluation of proton pump inhibitor use on treatment outcomes with ledipasvir and sofosbuvir in a real-world cohort study.

Many patients with chronic hepatitis C virus (HCV) are on prolonged proton-pump inhibitor (PPI) therapy and wish to remain on PPI therapy once treatment for HCV starts. A preliminary report recently suggested decrease rates of sustained virological response (SVR) for patients taking concomitant PPI and ledipasvir/sofosbuvir (LDV/SOF). We sought to determine the effect of PPI use on the rate of SVR in a real-world cohort of 1,979 patients with chronic HCV treated with LDV/SOF. We collected clinical data and pharmacy dispensing records on patients taking 8, 12, or 24 weeks of LDV/SOF ± ribavirin (RBV). The primary outcome was sustained virological response at 12 weeks after treatment completion (SVR12) in a per-protocol analysis in order to determine the effect of PPI use adjusted for confounders. Statistical adjustment was performed in propensity-matched analysis. Among treatment completers, SVR12 was achieved in 441 (97.1%) of PPI recipients compared with 1,497 (98.2%) in PPI nonrecipients (P = 0.19). Neither low- nor high-dose PPI was associated with decreased SVR, although patients taking twice-daily PPI achieved a lower SVR12 rate (91.2%; 95% confidence interval [CI], 77.0-97.0; P = 0.046). After propensity matching for PPI use, there were no significant associations between SVR12 and any dose or frequency of PPI use. However, in a sensitivity analysis focusing on patients with cirrhosis, twice-daily PPI use was associated with lower odds ratio for SVR12 (0.11; 95% CI, 0.02-0.59). CONCLUSION: These data from a cohort of real-world patients receiving hepatitis C antibody therapy with LDF/SOF ± RBV support the prescription labeling suggesting that patients take no more than low-dose (20-mg omeprazole equivalents) PPI daily. (Hepatology 2016;64:1893-1899).

Neoadjuvant therapy for rectal cancer decreases the number of lymph nodes harvested in operative specimens.

BACKGROUND: We evaluated the effect of neoadjuvant therapy (NAT) on lymph node harvest in rectal cancer patients undergoing anatomic resection with curative intent. METHODS: A prospectively maintained database was retrospectively queried for rectal cancer cases from 1990 to 2010. Demographic data, NAT, and lymph node yield were analyzed. Nonanatomic resections were excluded. RESULTS: Five hundred two cases were identified; the mean age was 68 years (range 34-89), and 56% were men. One hundred fifty-one (30%) patients received NAT. Overall, the lymph node yield was diminished in proctectomy specimens after NAT (mean = 9, median = 7) compared with specimens without therapy (mean = 13, median = 10, P = .001). Age was not a significant factor in the lymph node yield (P = .213 and .329). Among patients treated with NAT, younger patients had a significantly lower lymph node yield (P < .0001). CONCLUSIONS: A decreased lymph node yield in proctectomy specimens from patients treated with NAT is consistent with prior studies. Younger patients had a greater reduction in lymph node harvest after NAT compared with senior patients.

Sexual function after treatment for rectal cancer: a review.

Sexual function is one element of QOL that may be significantly altered following treatment for rectal cancer, but the incidence and contributing risk factors are generally poorly understood. Nevertheless, the impact of rectal cancer therapy on sexual function should be conveyed to patients preoperatively. In addition to helping patients evolve realistic expectations, it will help clinicians identify those for whom interventions may be appropriate. In the past 10 years, there has been an increase in the number of studies reporting sexual dysfunction following rectal cancer treatment. However, these studies are difficult to interpret collectively for a variety of reasons. Most importantly, sexual dysfunction lacks a standardized definition, which leads to poor comparability between studies. The best inclusive definitions describe sexual dysfunction as a collection of distinct symptoms, which differ for men and women. The absence of sexual activity is sometimes used as a surrogate for sexual dysfunction, but this is confounded by an individual's desire and opportunity for sexual activity, and may not be an accurate reflection of physiologic functionality. Additional factors complicating assimilation of studies include the absence of baseline data, missing data, small sample sizes, and heterogeneity in use of validated and nonvalidated instruments. The purpose of this article is to systematically review the contemporary literature reporting sexual function after rectal surgery to determine the overall risk of sexual dysfunction, evaluate possible contributing factors, and identify questions that should be addressed in future studies.