Deletions account for 17% of pathogenic germline alterations in MLH1 and MSH2 in hereditary nonpolyposis colorectal cancer (HNPCC) families.

Hereditary nonpolyposis colorectal cancer (HNPCC) is due to defects in DNA mismatch repair (MMR) genes MSH2, MLH1, MSH6, and to a lesser extent PMS2. Of 466 suspected HNPCC families, we defined 54 index patients with either tumors of high microsatellite instability (MSI-H) and/or loss of expression for either MLH1, MSH2, and/or MSH6, but without a detectable pathogenic point mutation in these genes. This study cohort was augmented to 64 patients by 10 mutation-negative index patients from Amsterdam families where no tumors were available. Deletion/duplication screening using the multiplex ligation-dependent probe amplification (MLPA) revealed 12 deletions in MSH2 and two deletions in MLH1. These deletions constitute 17% of pathogenic germline alterations but elucidate the susceptibility to HNPCC in only 22% of the mutation-negative study cohort, pointing towards other mutation mechanisms for an inherited inactivation of MLH1 or MSH2. We describe here four novel deletions. One novel and one known type of deletion were found for three and two unrelated families, respectively. MLPA analysis proved a reliable method for the detection of genomic deletions in MLH1 and MSH2; however, sequence variations in the ligation-probe binding site can mimic single exon deletions.

Ventral rectus fascia closure on top of mesh hernia repair in the sublay technique.

Sublay prosthetic herniorrhaphy has become a widely accepted procedure for incisional hernias. To evaluate the effect of fascia closure on top of mesh repair on infection, and the recurrence rate, the authors reviewed their data regarding herniorrhaphy in the sublay technique. This study was a retrospective analysis of 175 consecutive patients who underwent hernia repair by implantation of prostheses by means of the Stoppa-Rives technique from December of 1994 to December of 2001. All 175 patients had the mesh implanted in the subfascial plane, 130 received a light-weight or heavy-weight polypropylene mesh (Vypro or Prolene) (74 percent), eight had a polyester mesh (Mersilene) (5 percent), and 37 had an expanded polytetrafluoroethylene patch (Gore-Tex) (21 percent). After sublay mesh positioning, the mesh could not be covered by the fascia in 50 cases; in 31 of these cases, a second mesh was placed into the fascial defect. To evaluate the influence of the fascia closing procedure on top of the sublay mesh, three groups were differentiated: initial fascia closure (n = 125), no fascia closure and concomitant mesh interposition (n = 31), and no fascia closure without mesh interposition (n = 19). After a mean follow-up of 20 months, 11 deep prosthetic infections (8 percent) and 15 hernia recurrences (9 percent) were observed. There was an increased risk of mesh infection when the fascia could not be closed, but there was no influence of fascia closure on hernia recurrence. When the fascia was left open, the placement of a second mesh inlay technique reduced mesh infection. The authors' data give evidence that closing the ventral fascia after mesh repair in the sublay position is beneficial. When the edges of the hernia defect could not be approximated, the suturing of a second mesh into the fascia defect was a useful tool for reducing the prosthetic infection rate; however, no significant influence on hernia recurrence was observed.