Copy Number Variations (CNVs) Account for 10.8% of Pathogenic Variants in Patients Referred for Hereditary Cancer Testing.

BACKGROUND/AIM: Germline copy number variation (CNV) is a type of genetic variant that predisposes significantly to inherited cancers. Today, next-generation sequencing (NGS) technologies have contributed to multi gene panel analysis in clinical practice. MATERIALS AND METHODS: A total of 2,163 patients were screened for cancer susceptibility, using a solution-based capture method. A panel of 52 genes was used for targeted NGS. The capture-based approach enables computational analysis of CNVs from NGS data. We studied the performance of the CNV module of the commercial software suite SeqPilot (JSI Medical Systems) and of the non-commercial tool panelcn.MOPS. Additionally, we tested the performance of digital multiplex ligation-dependent probe amplification (digitalMLPA). RESULTS: Pathogenic/likely pathogenic variants (P/LP) were identified in 464 samples (21.5%). CNV accounts for 10.8% (50/464) of pathogenic variants, referring to deletion/duplication of one or more exons of a gene. In patients with breast and ovarian cancer, CNVs accounted for 10.2% and 6.8% of pathogenic variants, respectively. In colorectal cancer patients, CNV accounted for 28.6% of pathogenic/likely pathogenic variants. CONCLUSION: In silico CNV detection tools provide a viable and cost-effective method to identify CNVs from NGS experiments. CNVs constitute a substantial percentage of P/LP variants, since they represent up to one of every ten P/LP findings identified by NGS multigene analysis; therefore, their evaluation is highly recommended to improve the diagnostic yield of hereditary cancer analysis.

A decade of laparoscopic appendectomy: presentation of 1,026 patients with suspected appendicitis treated in a single surgical department.

BACKGROUND: The laparoscopic approach for suspected appendicitis is increasingly gaining acceptance. Nevertheless, the discussion on its safety, efficacy, indications, and diagnostic accuracy remains open. METHODS: During the decade 1993-2003, 1026 patients with suspected appendicitis were approached by laparoscopy. Sixty-three patients (6.1%) had chronic recurrent symptoms. Data were collected retrospectively and analyzed. There were 587 female and 439 male patients. Fertile women were compared to all other patients with respect to the diagnostic accuracy of laparoscopy. RESULTS: Conversion rate was 0.55%. Median operating time was 26 minutes. Overall complication rate was 5.7%, consisting mostly of minor complications. There were no major intraoperative complications. Wound infections and intra-abdominal abscesses were reviewed separately and were 1.1% and 0%, respectively. Diagnosis could be established via laparoscopy in 89% of all patients, 85.4% of fertile women, and 93.1% of patients except fertile women. A median of 4 minor analgesics and 2 narcotics were required after surgery. The median time until bowel movements, intake of solid food, and the median length of hospital stay were 24, 48, and 30 hours, respectively. Patients returned to normal activity after a median of 7 days. There was no mortality. There was 1 reoperation. Follow-up lasted 4 weeks. CONCLUSION: Laparoscopic appendectomy is a well-justified procedure in the treatment of acute and chronic appendicitis. If there is enough experience, patients can profit from a higher diagnostic accuracy, quicker return of bowel habits, less postoperative pain, shorter hospital stay, and a faster return to normal activities than is reported for the open procedure. Especially, fertile women can profit from these advantages. This abstract has been presented as a poster in the SAGES Conference 2004.