SLX4 interacts with RTEL1 to prevent transcription-mediated DNA replication perturbations.

The SLX4 tumor suppressor is a scaffold that plays a pivotal role in several aspects of genome protection, including homologous recombination, interstrand DNA crosslink repair and the maintenance of common fragile sites and telomeres. Here, we unravel an unexpected direct interaction between SLX4 and the DNA helicase RTEL1, which, until now, were viewed as having independent and antagonistic functions. We identify cancer and Hoyeraal-Hreidarsson syndrome-associated mutations in SLX4 and RTEL1, respectively, that abolish SLX4-RTEL1 complex formation. We show that both proteins are recruited to nascent DNA, tightly co-localize with active RNA pol II, and that SLX4, in complex with RTEL1, promotes FANCD2/RNA pol II co-localization. Importantly, disrupting the SLX4-RTEL1 interaction leads to DNA replication defects in unstressed cells, which are rescued by inhibiting transcription. Our data demonstrate that SLX4 and RTEL1 interact to prevent replication-transcription conflicts and provide evidence that this is independent of the nuclease scaffold function of SLX4.

Factors associated with complications of open versus laparoscopic sigmoid resection for diverticulitis.

BACKGROUND: This study critically reviews sigmoid colon resection for diverticulitis comparing open and laparoscopic techniques. METHODS: We conducted a retrospective review of all open and laparoscopic cases of diverticulitis between 1992 and 2001. Data analyzed included the following: indications for operation, postoperative complications, and incidence of laparoscopic conversion to laparotomy. Major and minor complications were analyzed in relation to patients' preoperative diagnosis, age, presence or absence of splenic flexure mobilization, length of stay, and laparoscopic sigmoid resection versus open sigmoid resection. RESULTS: Over a 10-year period, 166 resections for diverticulitis were performed including 126 open cases and 40 laparoscopic cases. No significant differences existed in patient characteristics between the groups. Major complications occurred in 14% of patients, and the laparoscopic conversion rate was 20%. The presence of abscess, fistula, or stricture preoperatively was associated with a higher complication rate only in patients > or =50 years old undergoing open sigmoid resection. The length of stay between patients undergoing laparoscopic resection was significantly less than in patients having open resection. CONCLUSION: Advanced laparoscopic sigmoid resection is an alternative to open sigmoid resection in patients with diverticulitis and its complications. Open sigmoid resection in patients >50 years may have a higher complication rate in complicated diverticulitis when compared with laparoscopic sigmoid resection (all patient ages) and open sigmoid resection (patients <50 years old). Regarding complications, no difference existed between the length of stay in patients with open vs. laparoscopic resection.

Harmonic Scalpel vs. electrocautery hemorrhoidectomy: a prospective evaluation.

INTRODUCTION: Management of posthemorrhoidectomy pain remains a very unsatisfactory clinical dilemma. Compared with electrocautery and laser, the Harmonic Scalpel causes minimal lateral thermal injury during tissue dissection. PURPOSE: The aim of the study was to establish whether decreased lateral thermal injury translated into diminished posthemorrhoidectomy pain. METHODS: A prospective randomized trial comparing Harmonic Scalpel hemorrhoidectomy and electrocautery was undertaken. Fifty consecutive patients were randomized into two groups: Harmonic Scalpels and electrocautery hemorrhoidectomy. The indications included Grade III internal hemorrhoids with external components or Grade IV disease. Patients with additional anorectal pathology (fissure or fistula) were excluded, as were patients with neurologic deficits, chronic pain syndrome, and those already taking narcotic analgesics. Pain was assessed using a visual analog scale preoperatively and on postoperative Days 1, 2, 7, 14, and 28. Twenty-four-hour narcotic usage (Hydrocodone, 10 mg) was recorded on postoperative Days 1, 2, 7, 14, and 28. A three-quadrant modified Ferguson hemorrhoidectomy was performed with each patient in the prone jackknife position. RESULTS: Pain in the Harmonic Scalpel hemorrhoidectomy group was significantly less than in electrocautery patients on each postoperative day studied. Analgesic requirements were also significantly less in the Harmonic Scalpel group on Days 1, 2, 7, and 14. There was no correlation between postoperative pain and grade of hemorrhoid, status of the surgical incision (open vs. closed), or any other study variable. Fifty-five percent of Harmonic Scalpel patients returned to work within one week of surgery, compared with 23 percent of electrocautery patients. CONCLUSION: The study demonstrates significantly reduced postoperative pain after Harmonic Scalpel hemorrhoidectomy compared with electrocautery controls. The diminished postoperative pain in the Harmonic Scalpel group likely results from the avoidance of lateral thermal injury.

Analysis of CA repeat polymorphisms places three human gene loci on the 8p linkage map.

The gene loci for luteinizing hormone-releasing hormone (LHRH), the beta-3 adrenergic receptor (ADRB3), and heregulin (HGL) have been assigned to the short arm of human chromosome 8, but the positions of these loci on the human genetic linkage map have not been previously reported. We have isolated simple tandem repeat polymorphisms (STRPs) for these loci. These STRPs enabled us to determine the genetic map locations for these genes.

Mapping of the pulmonary surfactant SP5 (SFTP2) locus to 8p21 and characterization of a microsatellite repeat marker that shows frequent loss of heterozygosity in human carcinomas.

We have identified 4 cosmids at the SFTP2 locus by cDNA hybridization. SFTP2 was mapped using a polymorphic CA repeat and localized to 8p21 by FISH. Allele loss in carcinomas was detected using this PCR marker. Among 11 lung and colon tumors, 6 of 9 informative cases exhibited allelic loss.

Laparoscopic surgery for colorectal neoplasms.

Laparoscopy is being used to assist in an increasing number and variety of bowel procedures. However, when being used for neoplastic disease concerns of margins and adequacy of mesenteric dissection must be addressed. We've performed 110 laparoscopic-assisted bowel procedures, with 45 of these performed for neoplastic disease. Ninety-two bowel resections were performed including 24 subtotal, total, or proctocolectomies. In this chapter we review the results of our series, as well as other reported series, and discuss some of the controversies involved with laparoscopy for neoplastic disease.

Effect of Wound Closure Technique on Wound Infection in the Morbidly Obese: results of a randomized trial.

The effect of suture obliteration of the subcutaneous dead space in morbidly obese abdominal wounds was studied in a randomized trial, comparing a pre-fascial retention suture technique (utilized for approximated of the thick panniculus) to controls where the skin was simply closed with staples. The wound infection rates were similar (11.8% for the sutured group versus 12.3% for controls, p 0.4), as were the total wound complication rates (26.5% for sutured group versus 21.9% for controls, p 0.4). Ultrasound study of the wounds closed without suturing the panniculus demonstrated no dead spaces. We conclude that no advantage is to be gained by suturing the subcataneous fat, however thick. The finding is of general application in wound closures involving thick layers of fat.

Pathogenesis of complications of percutaneous endoscopic gastrostomy. A lesson in surgical principles.

In two comparable series of percutaneous endoscopic gastrostomy differing in only one technical detail, complications were significantly reduced by omitting traction on the gastrostomy tube to approximate the gastric to the abdominal wall. Radiologic studies show that traction shortened the tract (4.9 +/- 1.1 cm with traction, 11.6 +/- 2.3 cm without traction). In two patients with fasciitis, gross pericatheter leak of contrast into a short and patulous tract was observed. Tube extrusion and gastrointestinal bleeding from gastric ersion ulcers were eliminated when traction was not used. No peritonitis occurred as a result of not attempting to approximate the stomach to the abdominal wall. The data suggest that traction on the gastrostomy tube is not only unnecessary, but is the cause of many of the complications reported.

Preoperative antibiotic soaking of silicone sponges. Does it make a difference?

A prospective randomized trial was carried out during the years 1974 to 1981 to determine whether preoperative antibiotic soaking of silicone sponges used in retinal detachment surgery would reduce the incidence of postoperative infection and extrusion. During this period 2972 consecutive primary scleral buckles were performed and in 921 (31%) of the cases an episcleral sponge was utilized either alone or in conjunction with a hard silicone encircling band. In alternate cases the sponge was soaked in an antibiotic solution for at least 30 minutes prior to insertion. In the remaining cases the sponge was not soaked. Overall, a statistically significant (P = 0.00018) seven-fold reduction in the rate of infection or extrusion was observed in cases where the silicone sponge was soaked preoperatively in antibiotics. An additional result of the study showed the rate of sponge removal was significantly increased by the use of multiple episcleral sponges (P = 0.00002).