Comparison of transvaginal natural orifice transluminal endoscopic surgery versus conventional surgery for uterosacral ligament suspension in patients who had concomitant vaginal hysterectomy for subtotal uterine prolapse.

INTRODUCTION: The study aimed to compare the short-term outcomes of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) for uterosacral ligament suspension (USLS) versus nonendoscopic USLS in patients with subtotal uterine prolapse who had a concomitant vaginal hysterectomy. METHODS: There were 51 patients who underwent vNOTES USLS, whereas the nonendoscopic conventional USLS group had 49 patients. The information about patient demographics, and perioperative data including the operative duration, blood loss, intraoperative and postoperative complications, and length of postoperative hospital stay were determined from the patients' files. Postoperative follow-up visits were scheduled at the first week and 1 month after surgery. RESULTS: The demographic variables including age, body mass index, menopausal status, and parity were comparable, and no significant differences were found. A total of 90.2% of the patients in the vNOTES group and 69.4% of the patients in the shull group were at menopause (p = .09). Operation time was significantly shorter in the shull group (p < .001), and the hospitalization period (p = .029) was significantly shorter in the vNOTES group. Ba, Bp, and D points and total vaginal length (TVL) were significantly behind the hymenal ring in patients who had vNOTES USLS procedure (p < .001). None of the patients who had intraoperative significant blood loss required transfusion. One patient in the vNOTES and two patients in the shull group had a postoperative cuff hematoma. CONCLUSION: vNOTES USLS has a good safety profile, higher percentage of adnexal surgeries with better improvement on POP-Q points Ba, Bp, D, and TVL compared with classic USLS in patients with subtotal uterine prolapse. Studies evaluating short- and long-term results of vNOTES versus conventional USLS are needed.

The effect of stress incontinence and pelvic organ prolapse surgery on sexual function and quality of life.

Objective: The objective of this study was to evaluate the sexual function and quality of life in female patients diagnosed with stress urinary incontinence (SUI) and pelvic organ prolapse (POP) after undergoing transobturator tape (TOT) or TOT with POP surgery and perineoplasty. Material and Methods: This prospective study population (n=86) consisted of sexually active women who had been diagnosed with SUI. Forty-six patients diagnosed with SUI with no POP (group 1) underwent TOT procedure only. Forty patients had a diagnosis of stage 2 and higher POP, based on POP quantification system with SUI (group 2). The second group was randomized as TOT-POP surgery (n=20) and TOT-POP surgery with perineoplasty (n=20). Prior to and six months after the surgical procedure, all female participants underwent assessment using the validated Urinary Distress Pre-Operative Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7), and Pelvic Organ Prolapse Incontinence Sexual Questionnaire (PISQ). Results: Post-operative IIQ-7 and UDI-6 scores were significantly lower for all three groups compared to the preoperative period, while a significant increase was observed in PISQ scores (p<0.01). The dissimilarity in preoperative and postoperative IIQ-7 and UDI-6 scores exhibited comparable results across the groups, whereas the variance in PISQ scores was notably greater in the TOT + POP surgery + perineoplasty group (p=0.03). Conclusion: Women with SUI or SUI with POP have better quality of life and sexual dysfunction after surgery. Perineoplasty may enhance sexual life in patients with perineal defect and vaginal enlargement.

Human Papillomavirus Infection (HPV) Prevalence in the Black Sea Region of Turkey: Primary HPV Screening for Cervical Cancer.

OBJECTIVE: Planning vaccination and treatment options requires knowledge about the regional incidence of human papillomavirus infection (HPV) and its genotypes. The aim of our study was to determine the regional prevalence of HPV with genotypic subclassification and to evaluate the efficacy of HPV testing in cervical screening.  Material and Method: This retrospective cohort study analyzed records of 10,152 women aged 30-65 from the On Dokuz Mayis University Medical Faculty's Gynecology Clinic, excluding those with a history of cervical disease, hysterectomy, or current pregnancy. Pre- and postmenopausal and total HPV prevalence were calculated. There was a total of 544 patients who underwent a colposcopic biopsy after cervical screening. The research focused on comparing the efficacy of Pap smears, HPV tests, and co-tests in detecting LSIL or more severe conditions, utilizing the BD Viper LT System for HPV screening and liquid-based cytology for smear tests. RESULTS: The prevalence of HPV in our region was determined to be 10.9%. When considering menopausal status, HPV prevalence was found to be 9.8% in premenopausal individuals and 12.4% in postmenopausal individuals. Evaluation of the pap smear results revealed a sensitivity of 74.8% for premenopausal and 81% for postmenopausal patients, with a specificity of 51% observed in both menopausal categories. In contrast, HPV testing demonstrated a sensitivity of 90.8% in premenopausal and 92.4% in postmenopausal individuals, with a specificity of 58% for both groups. The co-test results indicated an even higher sensitivity, with 97.9% in premenopausal and 100% in postmenopausal individuals, albeit with a reduced specificity of 28% in both cases. When identifying LSIL (low-grade squamous intraepithelial lesions) and more severe conditions, the sensitivity and specificity of the primary HPV test surpassed those of the pap smear. While the primary HPV test's sensitivity is markedly lower compared to the co-test, it boasts a significantly higher specificity. CONCLUSION: Regional HPV prevalence studies are valuable for the implementation of screening policies. The primary HPV DNA test is a reliable method for detecting preinvasive and invasive lesions in patients over 30 years of age.

Safety of Laparoscopic Entry Points in Patients With a History of Abdominal Surgery: A Research Article.

INTRODUCTION: This study aimed to assess the safety of laparoscopic entry sites in patients with previous abdominal surgery who subsequently required re-operation. MATERIAL AND METHODS: This is a prospective study wherein the data of 118 patients who had undergone previous abdominal surgery and were subsequently re-operated at our center (Bakirköy Doctor Sadi Konuk Research and Study Hospital) were collected from October 2015 to October 2016. Careful attention was paid to gathering information regarding patients' age, parity, body mass index (BMI), type of previous surgery, type of incision made during previous surgery, and medical history. For this study, the abdomen was topographically divided into nine parts. During the operation, all quadrants were examined and evaluated for adhesion and the content of adhesion. RESULTS: Adhesions were found in 44% (55 out of 118) of the patients, while 56% (66 patients) had no adhesions in the abdomen. The majority of cases (74%) had a history of cesarean section, and 87% had a Pfannenstiel incision. Adhesions were reported in 37.5% (33 out of 88) of the patients with a previous history of cesarean section. A significant proportion of subjects with adhesion (83%) had anterior abdominal wall adhesions, including only the omentum, whereas 11.5% (six subjects) had umbilical adhesions. Subjects with a history of umbilical hernia repair had more adhesions. DISCUSSION: The present study sought to assess the safety of laparoscopic entry points in individuals with prior abdominal surgery. The rise in laparoscopic surgeries, favored for reduced wound infections and quicker recovery times, brings forth concerns about potential complications in those with previous abdominal operations. Historically, postoperative adhesions have been observed in a significant number of patients after gynecological procedures. Our research, however, found a lower adhesion rate, which could be due to the smaller size of our sample and fewer gynecological cases. Existing adhesions can complicate subsequent surgeries, increasing operational times and posing injury risks. Adhesions also elevate healthcare costs and patient morbidity and mortality. Moreover, complications like Trocar-related injuries, including damage to major organs, are pivotal. While certain trocar insertion techniques may have fewer complications, our results align with previous findings suggesting higher adhesion rates after non-gynecological surgeries. Therefore, alternative entry points or methods, such as the palmer site or direct trocar entry, are recommended for those with an abdominal surgery history. Notably, our study's limited sample size may affect its generalizability, urging future studies for broader insights. Comprehensive pre-surgery assessments are crucial to anticipate complications. Our research supports that laparoscopic surgeries are safe for many with prior abdominal surgery, but for certain patients, non-umbilical entry sites are advised to further mitigate risks. CONCLUSION: The umbilicus is one of the safest entry sites for primary trocar insertion in patients with a history of Pfannenstiel incision. However, the probability of umbilical adhesions is high in patients who have undergone umbilical mesh repair, median incision, or major abdominal surgery. In these patients, surgeons should prefer other laparoscopic entry sites, especially Palmer's point, rather than the umbilicus.

An alternatively spliced PD-L1 isoform PD-L1∆3, and PD-L2 expression in breast cancers: implications for eligibility scoring and immunotherapy response.

Targeting PD-1/PD-L1 has shown substantial therapeutic response and unprecedented long-term durable responses in the clinic. However, several challenges persist, encompassing the prediction of treatment effectiveness and patient responses, the emergence of treatment resistance, and the necessity for additional biomarkers. Consequently, we comprehensively explored the often-overlooked isoforms of crucial immunotherapy players, leveraging transcriptomic analysis, structural modeling, and immunohistochemistry (IHC) data. Our investigation has led to the identification of an alternatively spliced isoform of PD-L1 that lacks exon 3 (PD-L1∆3) and the IgV domain required to interact with PD-1. PD-L1∆3 is expressed more than the canonical isoform in a subset of breast cancers and other TCGA tumors. Using the deep learning-based protein modeling tool AlphaFold2, we show the lack of a possible interaction between PD-L1∆3 and PD-1. In addition, we present data on the expression of an additional ligand for PD-1, PD-L2. PD-L2 expression is widespread and positively correlates with PD-L1 levels in breast and other tumors. We report enriched epithelial-mesenchymal transition (EMT) signature in high PD-L2 transcript expressing (PD-L2 > PD-L1) tumors in all breast cancer subtypes, highlighting potential crosstalk between EMT and immune evasion. Notably, the estrogen gene signature is downregulated in ER + breast tumors with high PD-L2. The data on PD-L2 IHC positivity but PD-L1 negativity in breast tumors, together with our results on PD-L1∆3, highlight the need to utilize PD-L2 and PD-L1 isoform-specific antibodies for staining patient tissue sections to offer a more precise prediction of the outcomes of PD-1/PD-L1 immunotherapy.

Comparison of Recurrence and Quality of Life Between Myoma Embolization and Myomectomy.

INTRODUCTION: Uterine myomas represent the most frequently diagnosed tumors among women of childbearing age. Symptoms often include profuse menstrual bleeding, diminished quality of life, and in some cases, infertility. The size and position of the fibroids typically influence the condition's manifestations. Moreover, symptomatology often varies depending on the fibroids' location. This investigation aimed to discern if there exists a significant correlation between life quality, reoccurrence rate, quality of life, and recurrence levels among patients who have undergone myomectomy and uterine fibroid embolization, respectively. METHODOLOGY: A retrospective cross-sectional study was conducted to compare the rates of recurrence and impacts on life quality between uterine fibroid embolization and myomectomy in women diagnosed with uterine myomas. Data were collected from 152 women who sought treatment at the Obstetrics and Gynecology clinic and also the Interventional Radiology clinic between January 2009 and January 2021. Thirteen participants were excluded due to the inability to maintain contact. The trial encompassed 76 patients who underwent myomectomy and 63 who had uterine fibroid embolization. In both groups, the life quality of 50 patients, five years postsurgery, was assessed using the UFS-QOL measure. Eligible participants were females between 20 and 40 years, with symptomatic Type 3-5 fibroids as per the FIGO classification, and with no comorbidities. Individuals under 20 or over 40 years, or those with fibroids classified as FIGO types 1,2,6,7,8, were not included. Other exclusion criteria included pregnancy status, abnormal endometrial biopsy results, abnormal smear tests, polyps, cancer, adenomyosis and coagulation disorders. RESULTS: The recurrence of fibroids was identified through symptomatology and diagnostic radiological methods. The recurrence rate was found to be 31.6% (n=24) for myomectomy patients and 14.3% (n=9) for those who underwent uterine fibroid embolization, with no statistically significant difference between the two groups (p > 0.05). The group subjected to myomectomy exhibited fewer symptoms, lower anxiety, and better physical mood scores. The myomectomy group displayed higher average anxiety scores (p<0.01). There were no significant disparities in control, consciousness, sexual function, or overall scores between the two groups. Symptoms and anxiety saw a marked reduction in the first postoperative year compared to the preoperative period (p<0.01). Compared to presurgery, energy, mood, awareness, and sexual function exhibited significant improvements in the first and fifth postoperative years (p<0.01). CONCLUSIONS: Our findings suggest a nonsignificant recurrence rate in the myomectomy group compared to the uterine artery embolization group. Notably, the decrease in symptom occurrence and anxiety following myomectomy was significantly favorable in terms of quality of life. While embolization was offered as a therapeutic option, myomectomy yielded more favorable results concerning quality of life.

A Giant Fibroepithelial Polyp of the Vulva.

Although vulvar lesions are mostly malignant, polyps represent one of the most frequent benign tumors of the vulva, typically measuring less than 5 cm in size. Larger lesions are uncommon and are likely the result of mesenchymal cell growth in the hormonally responsive subepithelial stromal layer of the lower genital tract. Typically, vulvar polyps are asymptomatic in their initial stages, and patients often delay seeking medical attention due to sociocultural factors. In this report, we present a case of a giant vulvar polyp and examine the underlying etiology and symptoms of this condition, highlighting the life stages of women that are most frequently affected. Additionally, we emphasize the rare but potential occurrence of malignant forms.

The Impact of Female Genital Mutilation on Sexual Function: A Study Conducted in Rural Sudan.

BACKROUND:  There are few studies comparing sexual function in women with female genital mutilation (FGM) in the literature, and most of these were evaluated with the Female Sexual Function Index (FSFI) questionnaire. Only one used the Female Genital Self-Image Scale (FGSIS) questionnaire. AIM: This study aims to evaluate the effects of FGM on sexual function in Sudanese women who did or did not undergo FGM, using the FSFI and FGSIS questionnaires. METHODS:  This descriptive study was conducted on Sudanese women from July 2020 to March 2021. Patients who attended to our hospital's gynecology outpatient clinic for health screening were included in this study. A total of 211 patients 113 with FGM and 98 without FGM were included in the study. The group with FGM was categorized according to the classification of the World Health Organization. The validated Arabic FSFI and FGSIS questionnaires were administered to groups with and without female genital mutilation and cutting (FGM/C). RESULTS: When the FGM types of the cases participating in the study were examined, patients with FGM were classified according to the FGM/C classification defined by the World Health Organization. They were classified as 20.4% (n=23) Type 1, 49.6% (n=56) Type 2, and 30.1% (n=34) Type 3. FSFI and FGSIS scores were significantly lower in the FGM/C group, especially in Type 3 with the highest tissue loss. The survey results statistically support the possibility of sexual dysfunction in FGM group. CLINICAL IMPLICATIONS: Female genital circumcision negatively affects sexual function. Therefore, clinicians should consider and sexual dysfunction in women with FGM attending primary care. Strengths and limitations: The strengths of this study are its originality, as it is the first study in the literature to use validated FGSIS and FSFI questionnaires together to assess sexual function in groups with and without FGM and to evaluate correlation of questionnaire results. We undertook the study it using validated and reliable scales, trained clinical staff, local staff gynecologist, and multivariate analysis. Limitation of the study is the chosen age range. The reason for limiting the age to under 35 is that we wanted to evaluate the more sexually active age group in our study. We cannot comment on the correlation of FSFI and FGSIS in circumcised patients over 35 years of age. CONCLUSION:  Sexual function and sexual self-image of women with FGM/C were found to be significantly lower compared to women without FGM when compared with the validated FSFI and FGSIS questionnaires.

Analyses of Copy Number Variations in Myxopapillary Ependymomas of Cauda Equina.

AIM: To identify the copy number variations that are specific to myxopapillary ependymomas (MPEs) of the cauda equina. MATERIAL AND METHODS: The patient cohort included five patients who underwent resection of histologically confirmed MPEs. Tumor samples collected during surgery and stored in liquid nitrogen as well as corresponding blood samples collected were analyzed. Genomic DNA from the venous blood and tumor samples was obtained using standard techniques and hybridized to a Cytoscan 750K Array in accordance with the manufacturer’s introductions. RESULTS: As a novel finding, amplification on chromosome 14q32.33 was detected in all tumor and blood samples, except one tumor sample. All tumor tissues also showed amplification on chromosomes 5, 7, 9, and 16. CONCLUSION: Although further studies with larger cohorts are required to identify genes involved in MPE tumorigenesis and to validate our results, these findings provide a basis for advanced molecular biological and genetic studies of MPEs.

Toward In Vitro Epigenetic Drug Design for Thyroid Cancer: The Promise of PF-03814735, an Aurora Kinase Inhibitor.

Thyroid cancer (TC) is a very common malignancy worldwide. Chief among the innovative molecular drug targets for TC are epigenetic modifications. Increased telomerase activity in cancer cells makes telomerase a novel target for epigenetic anticancer drug innovation. Recently, telomerase reverse transcriptase (TERT) gene promoter (TERTp) mutations (C228T and C250T) were reported at high frequency in TC cell lines and tumor biopsies. In this study, three representative TC cell lines, mutant TERTp (TPC1), mutant BRAF/TERTp (KTC2), and wild-type TERTp (WRO), were screened with a drug library composed of 51 epigenetic drugs: 14 Aurora kinase inhibitors; 23 histone deacetylase inhibitors; 5 sirtuin modifiers; 3 hypoxia-inducible factor inhibitors; 2 DNA methyltransferase inhibitors; 2 histone methyltransferase inhibitors, a histone demethylase inhibitor, and a bromodomain inhibitor. Effects of the drugs on cell growth at 48 and 72 h were compared. PF-03814735, a small-molecule inhibitor of Aurora kinase A (IC50 = 0.8 nM) and B (IC50 = 5 nM), was the most potent on KTC2 cells, whereas CUDC-101, a multitarget inhibitor, was effective on both WRO and KTC2 cells. Notably, PF-03814735 was found to be the most effective epigenetic drug on cell lines harboring the C228T mutation. In conclusion, these new findings offer specific guidance on dose and time course selection to design novel therapeutic interventions against TC using PF-03814735, and specifically target cells carrying the TERTpC228T mutation. In a larger context of drug discovery science, these findings inform new strategies to forecast optimal treatment regimens for TC, particularly with Aurora kinase inhibitors and in ways guided by epigenetic drug design.

Role of FLT3 in the proliferation and aggressiveness of hepatocellular carcinoma.

BACKGROUND/AIM: Previously we showed that Fms-like tyrosine kinase (FLT3) changes its cellular localization upon partial hepatectomy, suggesting a role in liver regeneration. FLT3 was also shown to play an important function in cellular proliferation and activation of PI3K and Ras. Thus, we aimed to investigate the role of FLT3 in hepatocellular tumorigenesis utilizing in vitro and in vivo models. MATERIALS AND METHODS: We used Snu398 cells that express FLT3. We investigated these cells' in vitro proliferation and invasion abilities by treatment with the FLT3 inhibitor K-252a or by knocking-down with FLT3 shRNA,. Furthermore, the effect of blocking FLT3 activity and expression during in vivo tumorigenesis was assessed with xenograft models. RESULTS: After K-252a treatment or stable knock-down, these cells' proliferation and migration abilities were highly diminished in vitro. In addition, significant diminution in tumorigenicity of Snu398 cells was also obtained in vivo. When FLT3 knocked-down Snu398 cells were injected into nude mice, we did not detect αSMA expression in these tumors, suggesting a role for FLT3 in in vivo invasiveness. CONCLUSION: Our data provided evidence that FLT3 has a crucial role both in hepatocarcinogenesis and its invasiveness. Therefore, targeting FLT3 and/or its activity may be a promising tool for combating hepatocellular carcinomas.

Chromosome 22q12.1 microdeletions: confirmation of the MN1 gene as a candidate gene for cleft palate.

We report on seven novel patients with a submicroscopic 22q12 deletion. The common phenotype constitutes a contiguous gene deletion syndrome on chromosome 22q12.1q12.2, featuring NF2-related schwannoma of the vestibular nerve, corpus callosum agenesis and palatal defects. Combining our results with the literature, eight patients are recorded with palatal defects in association with haploinsufficiency of 22q12.1, including the MN1 gene. These observations, together with the mouse expression data and the finding of craniofacial malformations including cleft palate in a Mn1-knockout mouse model, suggest that this gene is a candidate gene for cleft palate in humans.

Association of Pre-miRNA-499 rs3746444 and Pre-miRNA-146a rs2910164 Polymorphisms and Susceptibility to Behcet's Disease.

MiRNAs and NFKB1 are well-known immune response and inflammation regulators. MiRNA gene polymorphisms may affect miRNA biogenesis and function and, may thus, lead to changes in the expression of hundreds of genes such as NFKB1. The aim of this study was to investigate the association of Behcet's disease (BD) with NFKB1 rs28362491, pre-miRNA-146a rs2910164, and pre-miRNA-499 rs3746444 polymorphisms, as well as the analysis of their single and combined effects on its susceptibility in a Turkish population. These polymorphisms were analyzed by using the polymerase chain reaction-restriction fragment length polymorphism method in 100 BD patients and 145 healthy control subjects. The results were analyzed statistically using Pearson chi-square (χ(2)) test and Fisher's exact test (two sided). According to genotype analysis, the frequencies of ins/ins genotype and ins allele of rs28362491 were considerably higher in BD patients. Also, miRNA-499 rs3746444 homozygous (TT) genotypes exibited a significantly higher risk in patients with BD (odds ratios [OR]=3.0, 95% confidence intervals [95% CI]=1.284-7.007, p=0.017). Moreover, the frequency of T allele of rs3746444 was a risk factor for BD (OR=1.562, 95% CI=1.087-2.24, p=0.015). In addition, significant differences were found between the groups concerning miRNA-146a rs2910164 polymorphism. Homozygous CC genotype and C allele of rs2910164 polymorphism were found to be protective factors against BD. The results of the combined genotype analysis showed no notable differences between the multiple comparisons of rs28362491-rs2910164 and of rs28362491-rs3746444 in patients and control groups. Our data demonstrate that homozygous CC genotype and C allele of rs2910164 polymorphism are protective factors against BD, but rs3746444 and rs28362491 polymorphisms in miRNA-499 and in NFKB1 promoter are involved in the genetic susceptibility of BD. In addition, TT and ins/ins genotypes may influence certain proinflammatory cytokines and, may thus, play a role in the pathogenesis of BD.

Translating biotechnology to knowledge-based innovation, peace, and development? Deploy a Science Peace Corps--an open letter to world leaders.

Scholarship knows no geographical boundaries. This science diplomacy and biotechnology journalism article introduces an original concept and policy petition to innovate the global translational science, a Science Peace Corps. Service at the new Corps could entail volunteer work for a minimum of 6 weeks, and up to a maximum of 2 years, for translational research in any region of the world to build capacity manifestly for development and peace, instead of the narrow bench-to-bedside model of life science translation. Topics for translational research are envisioned to include all fields of life sciences and medicine, as long as they are linked to potential or concrete endpoints in development, foreign policy, conflict management, post-crisis capacity building, and/or peace scholarship domains. As a new instrument in the global science and technology governance toolbox, a Science Peace Corps could work effectively, for example, towards elucidating the emerging concept of "one health"--encompassing human, environmental, plant, microbial, ecosystem, and planet health--thus serving as an innovative crosscutting pillar of 21(st) century integrative biology. An interdisciplinary program of this caliber for development would link 21(st) century life sciences to foreign policy and peace, in ways that can benefit many nations despite their ideological differences. We note that a Science Peace Corps is timely. The Intergovernmental Panel on Climate Change (IPCC) of the United Nations released the Fifth Assessment Report on March 31, 2014. Worrisomely, the report underscores that no person or nation will remain untouched by the climate change, highlighting the shared pressing life sciences challenges for global society. To this end, we recall that President John F. Kennedy advocated for volunteer work that has enduring, transgenerational, and global impacts. This culminated in establishment of the Peace Corps in 1961. Earlier, President Abraham Lincoln aptly observed, "nearly all men can stand adversity, but if you want to test a man's character, give him power." We therefore petition President Barack Obama, other world leaders, and international development agencies in positions of power around the globe, to consider deploying a Science Peace Corps to cultivate the essential (and presently missing) ties among life sciences, foreign policy, development, and peace agendas. A Science Peace Corps requires support by a credible and independent intergovernmental organization or development agency for funding, and arbitration in the course of volunteer work when the global versus local (glocal) value-based priorities and human rights intersect in synergy or conflict. In all, Science Peace Corps is an invitation to a new pathway for competence in 21(st) century science that is locally productive and globally competitive. It can open up scientific institutions to broader considerations and broader inputs, and thus cultivate vital translational science in a world sorely in need of solidarity and sustainable responses to the challenges of 21(st) century science and society.

Mdm2 Snp309 G allele displays high frequency and inverse correlation with somatic P53 mutations in hepatocellular carcinoma.

Loss of function of the p53 protein, which may occur through a range of molecular events, is critical in hepatocellular carcinoma (HCC) evolution. MDM2, an oncogene, acts as a major regulator of the p53 protein. A polymorphism in the MDM2 promoter, SNP309 (T/G), has been shown to alter protein expression and may thus play a role in carcinogenesis. MDM2 SNP309 is also associated with HCC. However, the role of SNP309 in hepatocarcinogenesis with respect to TP53 mutations is unknown. In this study, we investigated the distribution of the MDM2 SNP309 genotype and somatic TP53 (the p53 tumor suppressor gene) mutations in 99 human HCC samples from Africa, Europe, China and Japan. Samples exhibited striking geographical differences in their distribution of SNP309 genotypes. The frequency and spectrum of p53 mutations also varied geographically; TP53 mutations were frequent in Africa, where the SNP309 T/T genotype predominated but were rare in Europe and Japan, where the SNP309 G allele was present more frequently. TP53 mutations were detected in 18% (4/22) of SNP309 T/G and G/G and 82% (18/22) of SNP309 T/T genotype holders; this difference was statistically highly significant (P-value=0.0006). Our results indicated that the presence of the SNP309 G allele is inversely associated with the presence of somatic TP53 mutations because they only coincided in 4% of HCC cases. This finding suggests that the SNP309 G allele may functionally replace p53 mutations, and in addition to known etiological factors, may be partly responsible for differential HCC prevalence.

Possible therapeutic role of vitamin D3 in aggressive fibromatosis.

Desmoids, also known as aggressive fibromatoses, are locally invasive tumors that are intermediate in their biological behavior that lies between benign fibrous proliferations and low-grade fibrosarcomas. In this report, we present a case of a young female patient with a huge tumoral mass located in the right shoulder region that recurred after total resection and was resistant to radio-chemo-hormonal therapy. Eventually, she responded to 1,25-(OH)(2)-vitamin D(3) treatment.