We have compared our local, pedicled, and free-flap reconstructions for 90 skull base defects performed over the past 10 years. The pericranial flap was found to provide a reliable dural seal. Free-flap reconstructions exhibited a significantly higher incidence of uncomplicated primary wound healing (95 versus 62.5 percent) and a much lower incidence of flap loss (0 percent), cerebrospinal fluid leak (5 percent), meningitis, and abscess (0 percent) when compared with defects reconstructed with pedicled myocutaneous flaps. We conclude that microvascular free-tissue transfer is the safest, most economical procedure when faced with moderate to large composite defects of the cranial base.
Radiation is the treatment of choice with surgery reserved for large tumors and extensive bone destruction. Long-term follow-up is essential because local recurrence and disseminated disease can occur many years postdiagnosis.
This information can be used by clinicians and researchers to understand the natural history of the patient group to critically assess both the selection bias and effectiveness of treatments.
We reviewed our experience with combined approaches to lesions that transcend the bones of the skull base. Seventy-seven skull base procedures were performed on 73 patients during a 10-year period from 1982 to 1992. There were 34 patients (44%) with region lesions (anterior), seven patients (9%) with region II lesions (anterior-lateral), 25 patients (32%) with region III lesions (lateral-posterior), and 11 patients (14%) with lesions that invaded more than one anatomic site. The histopathology in this series was quite variable, with 22 patients (29%) having squamous cell carcinoma and eight patients (10%) having basal cell carcinoma. Forty-one patients had surgery by an anterior approach and 38 patients had lateral approaches, with 18 undergoing an infratemporal approach and 29 undergoing temporal bone resections. Overall, 44% of the patients had a postoperative complication. Survival of this heterogeneous group of patients is 79% at 2 years and 71% at 4 years, with those patients with region II disease having a statistically significant poorer prognosis with no survivors at 4 years.
To examine the indications for, and the success of, free flap reconstruction in patients with forehead and scalp defects. Design: Case series. Setting: Two tertiary referral university teaching hospitals. Patients: Twenty-six consecutive patients, aged 31 to 85 years, presenting with 26 scalp defects, 5 forehead defects, and 1 combined defect (size, 70-672 cm 2). Three patients required resection and repair of the dura at surgery. Intervention: Patients were staged according to the size of the defect and the viability of surrounding tissue; free flap reconstruction was performed where indicated. Main Outcome Measures: Flap survival, complications, and disease-free and overall survival. Results: Thirty-four free flap reconstructions were performed (24 latissimus dorsi free flaps, 4 scapular free flaps, 3 rectus abdominis free flaps, and 3 radial forearm free flaps). One failed 2 weeks postoperatively, and 2 required exploration (1 for arterial ischemia and 1 for a hematoma). There were 3 cases of donor site morbidity (2 early seromas and 1 late abdominal hernia). One patient died of a pulmonary embolus 1 week postoperatively. Disease-free survival was 48% at 5 years and overall survival was 59% at 5 years, with a median follow-up of 24 months. Conclusions: Free revascularized tissue transfer is a reliable and safe way of reconstructing large scalp or forehead defects after traumatic injury or neoplastic resection. The muscle-only latissimus dorsi free flap for scalp reconstruction and the cutaneous scapular free flap for the forehead have proved successful in selected patients with a low complication rate and satisfactory cosmesis.
BackgroundEndometrial cancer is the most common gynecologic malignancy, and its incidence and associated mortality are increasing. Despite the immediate need to detect these cancers at an earlier stage, there is no effective screening methodology or protocol for endometrial cancer. The comprehensive, genomics-based analysis of endometrial cancer by The Cancer Genome Atlas (TCGA) revealed many of the molecular defects that define this cancer. Based on these cancer genome results, and in a prospective study, we hypothesized that the use of ultra-deep, targeted gene sequencing could detect somatic mutations in uterine lavage fluid obtained from women undergoing hysteroscopy as a means of molecular screening and diagnosis.Methods and FindingsUterine lavage and paired blood samples were collected and analyzed from 107 consecutive patients who were undergoing hysteroscopy and curettage for diagnostic evaluation from this single-institution study. The lavage fluid was separated into cellular and acellular fractions by centrifugation. Cellular and cell-free DNA (cfDNA) were isolated from each lavage. Two targeted next-generation sequencing (NGS) gene panels, one composed of 56 genes and the other of 12 genes, were used for ultra-deep sequencing. To rule out potential NGS-based errors, orthogonal mutation validation was performed using digital PCR and Sanger sequencing.Seven patients were diagnosed with endometrial cancer based on classic histopathologic analysis. Six of these patients had stage IA cancer, and one of these cancers was only detectable as a microscopic focus within a polyp. All seven patients were found to have significant cancer-associated gene mutations in both cell pellet and cfDNA fractions. In the four patients in whom adequate tumor sample was available, all tumor mutations above a specific allele fraction were present in the uterine lavage DNA samples. Mutations originally only detected in lavage fluid fractions were later confirmed to be present in tumor but at allele fractions significantly less than 1%. Of the remaining 95 patients diagnosed with benign or non-cancer pathology, 44 had no significant cancer mutations detected. Intriguingly, 51 patients without histopathologic evidence of cancer had relatively high allele fraction (1.0%–30.4%), cancer-associated mutations. Participants with detected driver and potential driver mutations were significantly older (mean age mutated = 57.96, 95% confidence interval [CI]: 3.30–∞, mean age no mutations = 50.35; p-value = 0.002; Benjamini-Hochberg [BH] adjusted p-value = 0.015) and more likely to be post-menopausal (p-value = 0.004; BH-adjusted p-value = 0.015) than those without these mutations. No associations were detected between mutation status and race/ethnicity, body mass index, diabetes, parity, and smoking status. Long-term follow-up was not presently available in this prospective study for those women without histopathologic evidence of cancer.ConclusionsUsing ultra-deep NGS, we identified somatic mutations in DNA extracted both from cell pellets...
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