The Pedicled Anterolateral Thigh Flap as a Versatile Option for Resurfacing Extensive Lower Trunk Defects.

BACKGROUND: The resurfacing of large abdominal and perineal defects is a major concern, and it poses a great challenge to the reconstructive surgeon. The main target in the reconstruction of the abdomen is to ensure a stable soft-tissue cover, and a strong and reliable fascia to prevent hernia recurrence and fecal contamination. The pedicled anterolateral thigh flap (ALT) either in the myocutaneous or fasciocutaneous form is a work-horse for the closure of abdominal and perineal defects. AIM: There is a paucity of studies on the use of the anterolateral thigh flap among black Africans especially in Nigeria; hence, we present our experience with the use of this flap for extensive abdominal and perineal defects. PATIENTS AND METHODS: The folders of all patients who had pedicled anterolateral thigh flap between January 2019 and July 2022 in our institution were reviewed. The patients' demographic data and the available details about the flap reconstruction were extracted from the folders. RESULTS: There were three males and two females, and the age range was between 22 and 48 years. Four cases resulted from tumor extirpation, while one was following extensive necrotizing fasciitis of the lower anterior abdominal wall. No gross anatomical variations were encountered intraoperatively. Four flaps had full survival, while one had marginal flap tip loss. CONCLUSION: The pedicled anterolateral thigh flap is an excellent reconstructive tool for the coverage of extensive abdominal and perineal defects.

Loss-of-Function GRHL3 Variants Detected in African Patients with Isolated Cleft Palate.

In contrast to the progress that has been made toward understanding the genetic etiology of cleft lip with or without cleft palate, relatively little is known about the genetic etiology for cleft palate only (CPO). A common coding variant of grainyhead like transcription factor 3 ( GRHL3) was recently shown to be associated with risk for CPO in Europeans. Mutations in this gene were also reported in families with Van der Woude syndrome. To identify rare mutations in GRHL3 that might explain the missing heritability for CPO, we sequenced GRHL3 in cases of CPO from Africa. We recruited participants from Ghana, Ethiopia, and Nigeria. This cohort included case-parent trios, cases and other family members, as well as controls. We sequenced exons of this gene in DNA from a total of 134 nonsyndromic cases. When possible, we sequenced them in parents to identify de novo mutations. Five novel mutations were identified: 2 missense (c.497C>A; p.Pro166His and c.1229A>G; p.Asp410Gly), 1 splice site (c.1282A>C p.Ser428Arg), 1 frameshift (c.470delC; p.Gly158Alafster55), and 1 nonsense (c.1677C>A; p.Tyr559Ter). These mutations were absent from 270 sequenced controls and from all public exome and whole genome databases, including the 1000 Genomes database (which includes data from Africa). However, 4 of the 5 mutations were present in unaffected mothers, indicating that their penetrance is incomplete. Interestingly, 1 mutation damaged a predicted sumoylation site, and another disrupted a predicted CK1 phosphorylation site. Overexpression assays in zebrafish and reporter assays in vitro indicated that 4 variants were functionally null or hypomorphic, while 1 was dominant negative. This study provides evidence that, as in Caucasian populations, mutations in GRHL3 contribute to the risk of nonsyndromic CPO in the African population.

Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations.

Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 × 10(-3)), 8q24 (rs987525, P = 1.22 × 10(-3)), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29 In conclusion, the authors have shown evidence for the association of many loci with NSCL/P and NSCPO. To the best of this knowledge, this study is the first to demonstrate any of these association signals in any African population.

Adult nephrectomy: our experience at Ile-Ife.

OBJECTIVES: To determine indications for adult nephrectomy in our community and the outcome of the procedure in our Institution. MATERIALS AND METHOD: Records of adult patients scheduled for nephrectomy at Obafemi Awolowo University Teaching Hospital from January 1993 to December 2004 were reviewed. Information extracted and analysed included age of patient, sex, presentation, investigations, indication, type and outcome of nephrectomy, histopathology result and duration of follow up. RESULTS: During the period, thirty adult patients mean age 42.73 yrs (range 16-80 yrs, M:F = 2:1) were scheduled for nephrectomy. Indications included suspicion of malignancy in 19 (63.3%) patients, protracted loin pain in non-functioning kidney in 2 (6.7%), uncontrollable bleeding in a patient with bilateral polycystic kidney (3.3%), pyonephrosis with septicaemia in a patient (3.3%), kidney injury (grade 5) in 2(6.7%) and kidney donation for transplantation in 3(10%). Ultrasound and intravenous urography were useful in the patients' evaluation. Twenty-seven (90%) patients were operated upon, but only 25 (83.3%) had nephrectomy. Sixteen (53.3%) had radical nephrectomy, 5 (16.7%) had simple nephrectomy, 3 (10%) had nephro-ureterectomy, and one (3.3%) had partial nephrectomy. Major surgical complications included wound sepsis (18.5%) and primary haemorrhage (7.4%). The overall morbidity and mortality rates were 7.4% and 3.7% respectively. Postuninephrectomy, patients' renal function remained stable after an average of 34.05 months follow-up. CONCLUSION: Renal tumours constitute the main indication for adult nephrectomy in our community. Kidney injury, kidney donation, and pyonephrosis are relatively uncommon indications. Open nephrectomy, which remains our local practice, is safe and unilateral nephrectomy is compatible with normal life.

Malignant renal tumors in adults: a ten-year review in a Nigerian hospital.

This study was undertaken to determine the age, sex, pattern of presentation, histopathology and outcome of management of adult patients with malignant renal tumors (MRT) in Nigeria. Using hospital records, a retrospective study was performed covering the period between January 1997 and December 2006. A total of 18 adult patients had been diagnosed to have MRT during this period. Information extracted and analyzed included the age of the patient, sex, presentation, investigations, type of histopathology, management and duration of follow-up. The mean age of the study patients was 47.5 years (range 16-80 yrs). The male: female ratio was 13 : 5 and the mean duration of symptoms was 43.6 weeks (range 2-104 wks). Sixteen patients (88.9%) presented in advanced stage. Symptoms included loin pain in 17 (94.4%), abdominal swelling in 15 (83.3%), weight-loss in 13 (72.2%) and hematuria in nine (50.0%). Ultrasound and intravenous urography assisted greatly in making the diagnosis. Thirteen patients (72.2%) underwent radical nephrectomy, tumors were not resectable in two (11.1%) and three others (16.7%) were deemed unfit to undergo surgery. The average tumor mass removed at surgery was 1.884 Kg (range 0.48-3.82 Kg). Renal cell carcinoma (RCC) accounted for 13 of the tumors (72.2%). Surgical complications include primary-hemorrhage, septicemia and tumor recurrence in one patient each (7.6%). Morbidity and mortality rates were 7.6% each. The average post-operative hospital stay and follow-up duration were 9.3 days and 37.5 months respectively. Our study suggests that RCC is the major MRT in our community. Most cases still present late with loin pain and swelling, weight loss and hematuria. This late presentation and sarcomatous type of tumor have negative influence on prognosis. Radical nephrectomy is beneficial in operable, locally advanced, non-metastatic MRT.