Does primary closure of direct inguinal hernia defect during laparoscopic mesh repair reduce the risk of early recurrence?

PURPOSE: Hernia recurrence is an important complication following inguinal hernia repair. Primary closure of ventral hernia defects laparoscopically has been shown to reduce the risk of recurrence and seroma formation. The results for ventral hernias may potentially be applied to direct inguinal hernias. Our aim was to evaluate the value of primary closure of direct defects during laparoscopic inguinal hernia mesh repair in reducing the incidence of early recurrence. METHODS: A retrospective, single-center cohort study was conducted on cases performed from August 2016 to February 2018. Patients with direct inguinal hernias undergoing elective laparoscopic mesh repair were included. When performed, the direct hernia defect was primarily closed with extracorporeal non-absorbable interrupted sutures followed by standard placement of a lightweight mesh covering myopectineal orifices. Early recurrence was defined as occurring within 1 year of surgery. RESULTS: A total of 75 direct inguinal hernias in 53 patients who underwent surgery and completed at least 1 year of follow-up were analyzed. The mean age of patients was 63 years (range 44-82 years); with majority of patients being male (98.1%). There were no significant differences observed between the two patient populations in terms of demographics, mean operative time and risk factors. In 9 (16.9%) patients, the direct hernias were recurrent hernias and all underwent open mesh repair during the index hernia surgery. The majority of hernia repairs (63 hernias in 45 patients, 85%) were performed via the totally extraperitoneal (TEP) approach. 19 patients (35.8%) with 28 direct inguinal hernias underwent primary closure of the direct defect prior to mesh placement; while, 34 patients (64.2%) with 47 direct hernias did not undergo primary closure. There were 3 direct hernia recurrences (6.4%) at 1 year post-operatively, and all occurred in the non-closure group. In comparison, there were no recurrences in the closure group; however, this difference was not statistically significant (p = 0.289) in our study due to the small sample size. CONCLUSION: Closure of direct inguinal hernia defects during laparoscopic mesh repair has been shown to reduce the incidence of early hernia recurrence in our retrospective study but future randomized controlled trials with large numbers would enable us to draw more robust conclusions and perhaps change the way we perform laparoscopic inguinal hernia repair.

Quantitative optical microscope with enhanced resolution using a pixelated liquid crystal spatial light modulator.

This paper presents a brief account of a novel optical microscope, which combines the advantages of two well-known techniques, namely phase contrast and phase stepping, to provide high contrast imaging and precision measurements. The inclusion of a programmable liquid crystal spatial light modulator provides for the phase stepping required, while also allowing flexibility for future improvements. The results shown reveal an important aspect of the system to facilitate quantitative sample measurements, with an enhancement of optical resolution compared with conventional optical imaging systems.

Phenylbutyrate-induced apoptosis and differential expression of Bcl-2, Bax, p53 and Fas in human prostate cancer cell lines.

OBJECTIVE: To assess the mechanisms of action of phenylbutyrate (PB), an investigational chemotherapeutic agent for prostate cancer (PCa), in apoptosis induction in PCa cell lines in vitro. STUDY DESIGN: We analyzed the differential expression of different apoptosis modulators, Bcl-2, Bax, p53 and Fas, for their potential role in PB-induced apoptosis using relative quantitative flow cytometry (FCM). Both androgen-dependent (LNCaP) and androgen-independent (C-4-2, PC-3-PF and DU145) human PCa cell lines were examined. RESULTS: PB induced apoptosis in PCa cell lines in a dose-dependent manner. Fifty percent apoptosis could be induced by 5-10 mM PB. Bcl-2 was down-regulated 30-75% and the Bax:Bcl-2 ratio elevated in apoptotic PCa cell lines regardless of their androgen dependency or p53 status. FCM revealed a heterogeneous stimulatory effect on the expression of Bax and Bcl-2 in PC3-PF cells at 0.5-2.5 mM PB. In a p53-positive cell line (DU145), p53 was repressed by 70% and Fas elevated sixfold with 10 mM PB. CONCLUSION: Our data show that PB-induced PCa apoptosis is associated with the relative repression of Bcl-2 and with up-regulation of Bax and Fas proteins and that this PB-induced apoptosis is independent of p53 and androgen-dependency status of PCa cell lines.

Cloning and characterization of UROC28, a novel gene overexpressed in prostate, breast, and bladder cancers.

A novel gene, designated UROC28, was identified by an agarose gel-based differential display technique, and it was found to be up-regulated in prostate, breast, and bladder cancer. Expression of UROC28 was also up-regulated in prostate cancer cells in the presence of androgens as demonstrated by relative quantitative reverse transcription-PCR. The elevated expression of this gene was observed to increase in surgically removed tissues concomitantly with rising Gleason grade and was most elevated in metastatic tissue. UROC28 protein was detected in serum by Western slot blot analyses, and a significant higher UROC28 protein level was found in sera of prostate cancer individuals compared with normal individuals and individuals with nonmalignant prostatic hyperplasia. Northern analyses in normal tissues showed that the UROC28 cDNA hybridizes to two mRNAs at about 2.1 and 2.5 kb. Nucleic acid sequence analyses indicated that these two alternatively spliced mRNA variants differ only at the 3' untranslated region. These two mRNAs encode the same protein with 135 amino acids. Bioinformation analyses suggest that there is a possible transmembrane domain from amino acid aa34 to aa50, three protein kinase-C phosphorylation sites at aa62 (SQK), aa89 (TMK), and aa94 (SMK), and one myristylation site at aa118 (GLECCL). Genomic Southern hybridization and chromosomal mapping demonstrated that UROC28 is encoded by a single copy of gene at chromosome 6q23-24. In situ hybridization and immunohistochemistry experiments further confirmed up-regulation of this gene in prostate and breast cancers with the expression localizing to the glandular epithelium. This gene did not demonstrate increased expression in lung and colon cancer tissues.

A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13-15, a region subject to LOH and rearrangement in human carcinoma cell lines.

The ETS transcription factors are a large family implicated in the control of cellular proliferation and tumorigenesis. In addition, chromosomal translocations involving ETS family members are associated with a range of different human cancers. Given the extensive involvement of ETS factors in tumorigenesis, it becomes important to identify any additional ETS genes that may also play oncogenic roles. We identify a novel gene, ELF5, that appears to belong to the ELF (E74-like-factor) subfamily of the ETS transcription factor family, based upon similarity within the 'ETS domain'. ELF5 displays a similar, but more restricted, expression pattern to that of the newly isolated epithelium-specific ETS gene, ELF3. Unlike most other ETS family members, ELF5 is not expressed in hematopoietic compartments, but is restricted to organs such as lung, stomach, kidney, prostate, bladder and mammary gland. ELF5 is localized to human chromosome 11p13-15, a region that frequently undergoes loss of heterozygosity (LOH) in several types of carcinoma, including those of breast, kidney and prostate. We find that ELF5 expression is not detectable in a number of carcinoma cell lines, some of which display loss or rearrangement of an ELF5 allele. Similar to other ETS family members, ELF5 displays specific binding to DNA sequences containing a GGAA-core. In addition, ELF5 is able to transactivate through these ETS sequences, present upstream from a minimal promoter. Our data suggest that ELF5 may play roles in mammary, lung, prostate and/or kidney function, and possibly also in tumorigenesis.

Interstitial Dup(1p) with findings of Kabuki make-up syndrome.

We describe a male patient with interstitial duplication of the short arm of chromosome 1 with breakpoints involving 1p13.1 and 1p22.1. The patient presented with some clinical findings of Kabuki make-up syndrome (KMS), including mental retardation, small head, eversion of the lateral part of lower eyelids, epicanthic folds, lateral flare of the eyebrows, short columella, and persistent fetal finger pads. This cytogenetic finding may provide clues for gene mapping of the syndrome.

A novel epithelial-expressed ETS gene, ELF3: human and murine cDNA sequences, murine genomic organization, human mapping to 1q32.2 and expression in tissues and cancer.

The ETS family of genes are implicated in cancers such as Ewings sarcoma, acute myeloid leukemia and chronic myelomonocytic leukemia. Further, they have important functions in embryonic development. Hence, identification and characterization of members of this family are important. We identify a novel ETS family member, ELF3, and report its human and murine cDNA sequences. The mouse cDNA has an alternatively spliced transcript with an extra 60 bp inserted. Hence we present the organization of the murine Elf3 gene together with its exon/intron structure. This gene consists of 9 exons and 8 introns spanning 4.8 kb. ELF3 binds and transactivates ETS sequences and interestingly also shows the ability to bind a GGAT-like purine core, a preferential ETS1/ETS2 type binding site. The expression of ELF3, unlike most other ETS family members, is absent in hematopoietic cells and hematopoietic organs in humans and mice. Intriguingly, the gene is specifically expressed in cell lines of epithelial origin and in organs such as lung, stomach, intestine, kidney that have specialized epithelial cells. We localize the human gene to 1q32.2, a region that is amplified in epithelial tumors of the breast, lung and prostate. Finally, we show that ELF3 expression is increased in a lung carcinoma and adenocarcinoma, as compared to normal tissue. ELF3 is also expressed in cell lines derived from lung cancers. These results suggest that this novel ETS gene may be involved in lung tumorigenesis.

Umbilical cord transforming growth factor-beta 3: isolation, comparison with recombinant TGF-beta 3 and cellular localization.

The transforming growth factor beta (TGF-beta) family of growth modulators play critical roles in tissue development and maintenance. Recent data suggest that individual TGF-beta isoforms (TGF-beta 1, -beta 2 and -beta 3) have overlapping yet distinct biological actions and target cell specificities, both in developing and adult tissues. The TGF-beta 3 isoform was purified to homogeneity from both natural and recombinant sources and characterized by laser desorption mass spectrometry, by protein sequencing, by amino acid analysis and by biological activity. TGF-beta 3 was the major TGF-beta isoform in umbilical cord (230 ng/g), and was physically and biologically indistinguishable from recombinant TGF-beta 3 and from the tumor growth inhibitory (TGI) protein found in umbilical cord. Immunohistochemistry using antipeptide TGF-beta 3 specific antibody showed TGF-beta 3 localization in perivascular smooth muscle.

Loss of heterozygosity on the short arm of chromosome 3 in nasopharyngeal carcinoma.

A consistent loss of constitutional heterozygosity within a specific chromosome locus in a tumor type is suggestive of a tumor suppressor gene important in the genesis of that tumor. We studied whether such genetic alterations are involved, in the development of nasopharyngeal carcinoma (NPC). Tumor and matched blood leukocytes DNA from eleven Hong Kong Chinese patients with primary NPC stages I to IV were subjected to restriction fragment length polymorphism (RFLP) analysis using chromosome 3-specific polymorphic probes. Such probes are assigned to chromosomal region 3p25 (RAF-1), 3p24-22.1 (ERBA beta), 3p21 (DNF15S2), 3p14 (D3S3), and 3q12 (D3S1). The breakpoint varied among tumors, ranging in extent from 3p21-14. However, 100% frequency of complete loss of heterozygosity was observed at two chromosomal loci: RAF-1 locus (ten of ten cases at 3p25) and D3S3 locus (nine of nine cases at 3p14), in all evaluable NPC patients, suggesting the presence of putative tumor suppressor gene(s) within or close to these defined regions. The observed consistent deletion of alleles on the short arm of chromosome 3 in the NPC cases, which is in line with our previously reported and present cytogenetic findings, may represent a critical event in the multistep genesis of NPC. The present report also identifies defined loci for linkage studies on NPC families.

Integration of HPV-16 DNA in cervical carcinoma cell line CC3/CUHK3 and its xenografts.

A recently established cell line, designated CC3/CUHK3, derived from a squamous cell carcinoma of the uterine cervix of a Hong Kong Chinese patient was investigated for its association with human papillomavirus (HPV) by Southern blot hybridization studies. A "grafted tumour" or xenograft of CC3/CUHK3 has also been successfully established in athymic mice, which showed similar histology to that of the original biopsy. The epithelial nature of the xenografts, like the original biopsy. The epithelial nature of the xenografts, like the original tumour specimen, was also confirmed by transmission electron microscopy which demonstrated the presence of desmosomes and tonofilaments. Moreover transmission electron microscopic examination revealed no HPV particle in either the tumour biopsy or the xenograft tissues. Analysis of the DNA samples extracted from the cervical cancer cell line and the xenograft tissues derived from it showed the presence of HPV type 16 DNA. No DNA sequence related to HPV type 6, 11, or 18 was demonstrated. The viral DNA was found to be integrated into the cellular genome at multiple sites as single copy or head-to-tail tandem repeats. Deletion or rearrangement of the HPV DNA had probably occurred on or subsequent to integration. Viral sequence deletion has also been observed in the grafted tumours derived from CC3/CUHK3.

Nontraumatic prehospital cardiac arrest ages 1 to 39 years.

Clinical and autopsy records were retrospectively reviewed for 105 patients between the ages of 1 and 39 years who came in to the emergency department with nontraumatic cardiac arrest. There were 65 male (62%) and 40 female patients (38%). Forty-eight percent of the patients were resuscitated. Long-term survival rate was 23%. The most common presenting rhythm was ventricular fibrillation (45%). Cardiac diseases constituted the most common cause of arrest (38%). Atherosclerotic coronary artery disease represented 50% of all cardiac causes. The second most common etiology was overdose or toxic exposure (21%). Witnessed arrest and an etiology of primary cardiac dysrhythmia for arrest were statistically significant factors related to favorable outcome. Asystole as the initial cardiac rhythm was a negative prognostic indicator. Age, sex, race, bystander cardiopulmonary resuscitation, and paramedic response time were not significant prognostic factors for long-term survival.

The optic nerve of the cat: appearance and loss of axons during normal development.

The number of axons in the optic nerve has been estimated in cats ranging in age from mid-gestation to adulthood. At mid-gestation the number of axons present in the nerve (218,000) already exceeded adult levels. The number of axons, nevertheless, more than doubled over the next 10-20 days, reaching a maximum of 450,000-483,000. In the last prenatal week and the first postnatal week, the number of axons declined rapidly, stabilizing at adult levels 2-3 weeks after birth. Myelination began just before birth and reached adult levels (over 95% of axons myelinated) 6-8 weeks after birth. Several mechanisms which may underlie the loss of axons are discussed.