Systematic review of cost-effectiveness studies on cervical cancer screening across Europe.

INTRODUCTION: Cervical cancer (CC) is a type of cancer with poor prognosis when diagnosed in advanced stage with a big socioeconomic burden. The incidence rates have wide variations among European countries depending on the implementation or not of screening, vaccination programs and the human development index (HDI). Most studies on cost-effectiveness of CC screening programs are carried out in countries with a high HDI, however more recent reviews of screening approaches are coming from countries with lower HDI aiming to identify the best screening strategies. Our study aims to identify which are the currently applied and most cost-effective strategies of CC screening in Europe. MATERIALS AND METHODS: This is a systematic review conducted in three different databases (PubMed, Scopus and ScienceDirect) and reported following the PRISMA guidelines. General key terms for all databases were the following: cost-effectiveness, cervical cancer, screening, Europe. We included studies in English, Italian, Spanish and Bulgarian, published in the last 25 years, reporting data on cost-effectiveness of CC screening, costs and outcome measures. The methodological quality of the articles was evaluated with a standardized tool. RESULTS: A total of 262 studies were identified and 22 studies were included in the final analysis. In 90.1 % of the economic studies, the new screening strategy was shown to be more cost-effective compared to the current one or compared to no screening. The optimal strategy mostly involved primary HPV testing, combined with cytology or as stand-alone screening technique. Several scenarios differing on starting age and periodicities for CC screening, combination of techniques and triage, were found to be cost-effective and below the willingness to pay (WTP) threshold. The methodology of all included studies was assessed from 10 to 11 on the JBI standardized tool and Drummond 11-point checklist. CONCLUSION: Numerous cost-effective options for CC screening in different European countries were identified in this systematic review. HPV testing, with or without cytology, mainly starting at 30 years of age and repeated every 5 years or more was the most cost-effective technique. Future studies should focus on the most appropriate CC screening approach for each context and setting, also considering HPV vaccination in Europe.

Prognostic factors for low- and high grade squamous intraepithelial lesions in histological preparations following LLETZ procedure.

OBJECTIVE: Aim: To investigate the influence of the following prognostic factors: age, parity, hormonal status (premenopausal, postmenopausal), histological result from targeted biopsy (LSIL, HSIL), adequacy of colposcopic examination (satisfactory, unsatisfactory colposcopy), type of TZ (type 1, 2, 3), type of cervical lesions (type 1, 2, 3), the colposcopic impression (diagnosis) of the cervical lesion (LSIL, HSIL/Ca colli uteri in situ), lesion size (up to 1/3; up to 2/3; more than 2/3 of the cervical circumference) for the occurrence of LSIL and HSIL/Ca colli uteri in situ in the final histological result after LLETZ procedure. PATIENTS AND METHODS: Materials and Methods: This is a prospective study (01.01.2017 - 31.07. 2021) including 189 patients with cervical precancerous lesions received LLETZ treatment One gynaecologic oncologist performed video colposcopy, targeted biopsy, and LLETZ. One histopathologist diagnosed histological specimens from the biopsy and LLETZ procedure. RESULTS: Results: We found a statistically significant correlation between the histological result of the targeted biopsy factor and the colposcopic diagnosis factor concerning the final histological result of LLETZ. The cervical lesion size factor and cervical lesion type factor have prognostic significance for the histological outcome following LLETZ. CONCLUSION: Conclusions: The histological result of targeted biopsy and colposcopic diagnosis are significant factors for the final histological result after LLETZ. Cervical lesion invasion into the endocervical canal is a prognostic factor for HSIL, and its invisible borders - for carcinoma (in situ or microinvasive/invasive). Lesion size up to 1/3 of the cervix is a prognostic factor for LSIL and large lesions (2/3 of the cervix) - for HSIL and cervical cancer (in situ, microinvasive/invasive).

Exploring Protein Post-Translational Modifications of Breast Cancer Cells Using a Novel Combinatorial Search Algorithm.

Post-translational modification of proteins plays an important role in cancer cell biology. Proteins encoded by oncogenes may be activated by phosphorylation, products of tumour suppressors might be inactivated by phosphorylation or ubiquitinylation, which marks them for degradation; chromatin-binding proteins are often methylated and/or acetylated. These are just a few of the many hundreds of post-translational modifications discovered by years of painstaking experimentation and the chemical analysis of purified proteins. In recent years, mass spectrometry-based proteomics emerged as the principal technique for identifying such modifications in samples from cultured cells and tumour tissue. Here, we used a recently developed combinatorial search algorithm implemented in the MGVB toolset to identify novel modifications in samples from breast cancer cell lines. Our results provide a rich resource of coupled protein abundance and post-translational modification data seen in the context of an important biological function-the response of cells to interferon gamma treatment-which can serve as a starting point for future investigations to validate promising modifications and explore the utility of the underlying molecular mechanisms as potential diagnostic or therapeutic targets.

Integrated Analysis of Phagocytic and Immunomodulatory Markers in Cervical Cancer Reveals Constellations of Potential Prognostic Relevance.

Despite improvements in vaccination, screening, and treatment, cervical cancer (CC) remains a major healthcare problem on a global scale. The tumor microenvironment (TME) plays an important and controversial role in cancer development, and the mechanism of the tumor's escape from immunological surveillance is still not clearly defined. We aim to investigate the expression of CD68 and CD47 in patients with different histological variants of CC, tumor characteristics, and burden. This is a retrospective cohort study performed on paraffin-embedded tumor tissues from 191 patients diagnosed with CC between 2014 and 2021 at the Medical University Pleven, Bulgaria. Slides for immunohistochemical (IHC) evaluation were obtained, and the expression of CD68 was scored in intratumoral (IT) and stromal (ST) macrophages (CD68+cells) using a three-point scoring scale. The CD47 expression was reported as an H-score. All statistical analyses were performed using R v. 4.3.1 for Windows. Infiltration by CD68-IT cells in the tumor depended on histological type and the expression of CD47. Higher levels of the CD47 H-score were significantly more frequent among patients in the early stage. Higher levels of infiltration by CD68-ST cells were associated with worse prognosis, and the infiltration of CD68-IT cells was associated with reduced risk of death from neoplastic disease. TME is a complex ecosystem that has a major role in the growth and development of tumors. Macrophages are a major component of innate immunity and, when associated with a tumor process, are defined as TAM. Tumor cells try to escape immunological surveillance in three ways, and one of them is reducing immunogenicity by the overexpression of negative coreceptors by T-lymphocytes and their ligands on the surface of tumor cells. One such mechanism is the expression of CD47 in tumor cells, which sends a "don't eat me" signal to the macrophages and, thus, prevents phagocytosis. To our knowledge, this is the first study that has tried to establish the relationship between the CD47 and CD68 expression levels and some clinicopathologic features in CC. We found that the only clinicopathological feature implicating the level of CD68 infiltration was the histological variant of the tumor, and only for CD68-IT-high levels were these observed in SCC. High levels of CD47 expression were seen more frequently in pT1B than pT2A and pT2B in the FIGO I stage than in the FIGO II and III stages. Infiltration by large numbers of CD68-IT cells was much more common among patients with a high expression of CD47 in tumor cells. A high level of infiltration by CD68-ST cells was associated with a worse prognosis, and a high level of infiltration by CD68-ST cells was associated with a lower risk of death from cancer.

Revisiting Querleu-Morrow Radical Hysterectomy: How to Apply the Anatomy of Parametrium and Pelvic Autonomic Nerves to Cervical Cancer Surgery?

In 2008, Querleu and Morrow proposed a novel classification of radical hysterectomy, which was quickly accepted by the professional oncogynecological community. The Querleu and Morrow (Q-M) classification of radical hysterectomy has provided a unique opportunity for uniform surgical and anatomical terminology. The classification offers detailed explanations of anatomical landmarks and resection margins for the three parametria of the uterus. However, there are still some disagreements and misconceptions regarding the terminology and anatomical landmarks of the Q-M classification. This article aims to highlight the surgical anatomy of all radical hysterectomy types within the Q-M classification. It discusses and illustrates the importance of anatomical landmarks for defining resection margins of the Q-M classification and reviews the differences between Q-M and other radical hysterectomy classifications. Additionally, we propose an update of the Q-M classification, which includes the implementation of parauterine lymphovascular tissue, paracervical lymph node dissection, and Selective-Systematic Nerve-Sparing type C2 radical hysterectomy. Type D was modified according to current guidelines for the management of patients with cervical cancer. The detailed explanation of the surgical anatomy of radical hysterectomy and the proposed update may help achieve surgical harmonization and precise standardization among oncogynecologists, which can further facilitate accurate and comparable results of multi-institutional surgical clinical trials.

Utility of expression of 4-hydroxynonenal tested by immunohistochemistry for cervical cancer.

Introduction: Cervical cancer (CC) is a leading cause of mortality in women around the world, with the highest incidence rate still being in developing countries. The most common aetiological factor is infection with high-risk human papilloma virus viral strains. Oxidative stress through generation of reactive oxygen species leads to lipid peroxidation and DNA damage. Studies show that reactive lipid electrophiles such as 4-hydroxynonenal (4-HNE) produced in the process play an important role in cancer signalling pathways and are a good biomarker for oxidative stress. We aim to investigate the prognostic role of 4-HNE as a biomarker for oxidative stress in patients in early and advanced stages of CC measured by immunohistochemistry. Material and methods: This is a retrospective study of 69 patients treated at our Department of Oncogynaecology. Paraffin embedded tumour tissues were immunohistochemically tested for the levels of expression of 4-HNE. The results for H-score, Allred score, and combined score were investigated for association with tumour size, lymph node status, andInternational Federation of Gynaecology and Obstetrics stage. Results: 4-hydroxynonenal showed higher expression in more advanced stages of CC and in cases with involved lymph nodes. Tumour size was not associated with the levels of 4-HNE. Conclusions: To best of our knowledge, this is the first study to use immunohistochemistry to examine the expression of 4-HNE as a prognostic factor in CC. The 3 score systems showed similar results. The pattern of 4-HNE histological appearance is dependent on the histological origin of cancer and is not universal.

Evaluation of cleaved caspase-3 and Ki-67 index on diagnostic biopsy in response to neoadjuvant chemotherapy in the context of post-treatment tumour ypT stage, ypN stage, grade, and molecular subtype.

Introduction: Breast carcinoma is a heterogeneous disease, characterised by diverse clinical behaviour. The aim of this study was to assess how cleaved caspase-3 and Ki-67 index, evaluated on diagnostic biopsy, are related to response to neoadjuvant chemotherapy in the context of molecular subtype, post-treatment tumour, N category, and grade. Material and methods: A retrospective analysis was carried out among 110 breast cancer patients. Ki-67 levels and caspase-3 expression on diagnostic biopsy were explored regarding their relation to tumour grade and molecular subtype, ypT, ypN categories, and T and N categories according to Sataloff tumour response evaluation. Results: A statistically significant relationship was found between Ki-67 levels and tumour grade K-W = 24.2932, p < 0.0001; molecular subtype K-W = 28.5439, p < 0.00000967538; size and invasion of the primary tumour after neoadjuvant chemotherapy K-W = 11.7944, p < 0.0377169; caspase-3 expression after neoadjuvant therapy, evaluated according to the Sataloff classification χ2 = 5.97, df = 1, p = 0.0145. Discussion: No significant difference was found between Ki-67 expression in patients with pathological complete response, compared to those with partial and no response, a statistically significant difference in cases with different molecular subtype, histology grade, and tumour stage after neoadjuvant therapy. Cleaved caspase-3-positive breast cancer cases are often better responders to neoadjuvant therapy, but with no significant correlation to molecular subtype, high-grade categories, or tumour stage. Conclusions: The caspase-3 and Ki-67 index on diagnostic biopsy are related to post-neoadjuvant treatment prognostic factors (ypT stage, grade), proving them useful for prediction of treatment response to neoadjuvant therapy and further patient management.

Primary Vaginal Mucinous Adenocarcinoma of Intestinal Type-Clinical, Radiological and Morphological Aspects.

Background and Objectives: Neoplasms of the vagina are rare and account for 1-2% of all tumors of the female reproductive system. Primary neoplasms of the vagina are most often carcinomas originating from squamous or glandular epithelium. Of the primary glandular tumors, clear cell, endometrioid, and serous adenocarcinomas are the most common types, while mucinous and mesonephric types are very rare. Mucinous adenocarcinoma is histologically subclassified into endocervical and intestinal types. We add to the existing literature another case of an extremely rare gynecological neoplasm-primary vaginal mucinous adenocarcinoma (PVMAC) intestinal type associated with vaginal villous adenoma with high-grade dysplasia. We discuss the clinical, radiological and morphological features of this rare entity. Materials and Methods: We report a case of a 59-year-old woman with PVMAC intestinal type associated with vaginal villous adenoma with high-grade dysplasia. The patient was evaluated with a gynecological exam, and biopsy, curettage and tumor excision were performed. The positron emission tomography-computed tomography (PET/CT) scan, at the level of the pelvis, supported the primary location of the disease. Histological and immunohistochemical methods were applied. Results: The gynecological examination of the vagina revealed an exophytic polypoid mass with a diameter of 3 cm, located on the posterior wall, in the area of introitus vaginae. The PET/CT scan revealed a hypermetabolic malignant formation involving the vagina and anal canal, without evidence of pelvic and inguinal lymphadenopathy, and also, it excluded disease at sites other than the vagina. The histological and immunohistochemical investigations, as well as the clinical and radiological data, lent support to the diagnosis "primary vaginal mucinous adenocarcinoma intestinal type". Conclusions: PVMAC intestinal type is a rare gynecological pathology, which presents a serious challenge for oncogynecologists, radiologists and pathologists.

Neglected Anatomical Areas in Ovarian Cancer: Significance for Optimal Debulking Surgery.

Ovarian cancer (OC), the most lethal gynecological malignancy, usually presents in advanced stages. Characterized by peritoneal and lymphatic dissemination, OC necessitates a complex surgical approach usually involving the upper abdomen with the aim of achieving optimal cytoreduction without visible macroscopic disease (R0). Failures in optimal cytoreduction, essential for prognosis, often stem from overlooking anatomical neglected sites that harbor residual tumor. Concealed OC metastases may be found in anatomical locations such as the omental bursa; Morison's pouch; the base of the round ligament and hepatic bridge; the splenic hilum; and suprarenal, retrocrural, cardiophrenic and inguinal lymph nodes. Hence, mastery of anatomy is crucial, given the necessity for maneuvers like liver mobilization, diaphragmatic peritonectomy and splenectomy, as well as dissection of suprarenal, celiac, and cardiophrenic lymph nodes in most cases. This article provides a meticulous anatomical description of neglected anatomical areas during OC surgery and describes surgical steps essential for the dissection of these "neglected" areas. This knowledge should equip clinicians with the tools needed for safe and complete cytoreduction in OC patients.

Relative Risk of Death in Bulgarian Cancer Patients during the Initial Waves of the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has led to millions of documented deaths worldwide, with diverse distribution among countries. Surprisingly, Bulgaria, a middle-income European Union member state, ranked highest in COVID-19 mortality. This study aims to assess whether Bulgarian cancer patients experienced a higher relative risk (RR) of death compared to the general Bulgarian population during the pandemic. MATERIALS AND METHODS: Data from the Bulgarian National Statistical Institute and the Bulgarian National Cancer Registry were analyzed to estimate monthly RR of death in cancer patients compared to the general population before and during the first two years of the pandemic. The impact of the COVID-19 waves and predominant SARS-CoV-2 variants on RR was evaluated on various cancer types and age groups using a multiple linear regression approach. RESULTS: During the COVID-19 waves, both the general population and cancer patients experienced a significant increase in mortality rates. Surprisingly, the RR of death in cancer patients was lower during pandemic waves. The results from the statistical modeling revealed a significant association between the COVID-19 waves and reduced RR for all cancer patients. Notably, the effect was more pronounced during waves associated with the Alpha and Delta variants. The results also showed varying impacts of the COVID-19 waves on RR when we analyzed subsamples of data grouped depending on the cancer type, age and sex. CONCLUSIONS: Despite increased overall mortality in Bulgarian cancer patients during the pandemic, the RR of death was lower compared to the Bulgarian general population, indicating that protective measures were relatively effective in this vulnerable group. This study underscores the importance of implementing and encouraging preventive measures, especially in cancer patients, to mitigate the impact of future viral pandemics and reduce excess mortality.

A rare case of angiomyomatous hamartoma in the pelvic and paraaortic lymph nodes.

Angiomyomatous hamartoma (AMH) of the lymph node is an extremely rare, benign vascular disease of unknown etiology. It is characterized by partial or complete replacement of the lymph node parenchyma by irregularly distributed, thick-walled blood vessels, smooth muscle bundles and adipose tissue in a fibrotic stroma. Angiomyomatous hamartoma occurs mainly in inguinal and femoral nodal regions, but there are a few reports of some other locations - submandibular, cervical, popliteal and paraaortic lymph nodes. We present a case of a 37-old female patient with AMH in the pelvic and paraaortic lymph nodes who presented with weight loss - 7 kg in 7 months. The differential diagnosis of AMH includes lymphangiomyomatosis, which, unlike AMH, involves primarily thoracic and intra-abdominal lymph nodes: nodal leiomyomatosis with less pronounced vascular proliferation and angiomyolipoma of the lymph node. The latter is composed of the same tissues as in AMH, but the smooth muscle component shows increased cellularity, polymorphism and increased mitotic activity, as well as a typical immune profile with coexpression of melanocyte markers and estrogen, which were negative in our case. The world literature references show that this is the first reported case in which the disease manifested itself with weight loss and affected paraaortic lymph nodes in a female patient.

Endometrial carcinoma in patients under 40 years of age: insights from the Bulgarian Cancer Registry.

OBJECTIVES: We aimed to investigate the overall survival (OS) of young women with endometrial cancer (EC) in Bulgaria and the impact of histological type on survival. MATERIAL AND METHODS: This is a population-wide retrospective study of patients with EC (≤ 40 years at diagnosis) registered at Bulgarian National Cancer Registry (BNCR) between 1993 and 2020. Patients were re-classified according to the 8th edition of the TNM classification. RESULTS: In total, 30 597 patients were registered and histologically confirmed with malignant tumors of the uterine body. From that, 29 065 of them (95%) had ECs, and the rest had sarcomas. Around 1.64% of all malignant tumors of the uterine body are diagnosed in women under the age of 40. Most of them are diagnosed in the early stage. There was no significant difference in median OS for patients diagnosed before or after 2003. In recent years there was a slight improvement in survival and patients from the last cohort of this study had a 5-year survival rate of 92.5%. Patients with favorable pathology (T1, G1/2) had no lymph node involvement at the time of diagnosis and their 10-year survival rate was 94%. CONCLUSIONS: EC in young women is a rare disease. In most cases, patients are diagnosed in early stageT1, G1/2, N0 and their prognosis is excellent. However, the lack of improvement of OS of young patients with EC in the last three decades shows the need for treatment optimization.

The Role of FBXW7 in Gynecologic Malignancies.

The F-Box and WD Repeat Domain Containing 7 (FBXW7) protein has been shown to regulate cellular growth and act as a tumor suppressor. This protein, also known as FBW7, hCDC4, SEL10 or hAGO, is encoded by the gene FBXW7. It is a crucial component of the Skp1-Cullin1-F-box (SCF) complex, which is a ubiquitin ligase. This complex aids in the degradation of many oncoproteins, such as cyclin E, c-JUN, c-MYC, NOTCH, and MCL1, via the ubiquitin-proteasome system (UPS). The FBXW7 gene is commonly mutated or deleted in numerous types of cancer, including gynecologic cancers (GCs). Such FBXW7 mutations are linked to a poor prognosis due to increased treatment resistance. Hence, detection of the FBXW7 mutation may possibly be an appropriate diagnostic and prognostic biomarker that plays a central role in determining suitable individualized management. Recent studies also suggest that, under specific circumstances, FBXW7 may act as an oncogene. There is mounting evidence indicating that the aberrant expression of FBXW7 is involved in the development of GCs. The aim of this review is to give an update on the role of FBXW7 as a potential biomarker and also as a therapeutic target for novel treatments, particularly in the management of GCs.

Surgical Anatomy of the Liver-Significance in Ovarian Cancer Surgery.

INTRODUCTION: Ovarian cancer is the leading cause of death among all gynecological malignancies. Most patients present with an advanced stage of the disease. The routes of spread in ovarian cancer include peritoneal dissemination, direct invasion, and lymphatic or hematogenous spread, with peritoneal and lymphatic spread being the most common among them. The flow direction of the peritoneal fluid makes the right subphrenic space a target site for peritoneal metastases, and the most frequently affected anatomical area in advanced cases is the right upper quadrant. Complete cytoreduction with no macroscopically visible disease is the most important prognostic factor. METHODS: We reviewed published clinical anatomy reports associated with surgery of the liver in cases of advanced ovarian cancer. RESULTS: The disease could disseminate anatomical areas, where complex surgery is required-Morrison's pouch, the liver surface, or porta hepatis. The aim of the present article is to emphasize and delineate the gross anatomy of the liver and its surgical application for oncogynecologists. Moreover, the association between the gross and microscopic anatomy of the liver is discussed. Additionally, the vascular supply and variations of the liver are clearly described. CONCLUSIONS: Oncogynecologists performing liver mobilization, diaphragmatic stripping, and porta hepatis dissection must have a thorough knowledge of liver anatomy, including morphology, variations, functional status, potential diagnostic imaging mistakes, and anatomical limits of dissection.

The effects of ROMO1 on cervical cancer progression.

INTRODUCTION: More than 95% of the cases of Cervical cancer (CC) are now linked to infection with Human papilloma virus (HPV) but the infection alone is not sufficient for starting the oncogenesis. Reactive Oxygen Species (ROS) can promote CC cancerogenesis. ROMO1 is a protein that regulates the production of intracellular ROS and influences cancer cell invasion and proliferation. We aimed to investigate the impact of ROS in CC progression, measured by the expression of ROMO1. METHODS AND MATERIALS: This is a retrospective study of 75 patients treated at the Department of Oncogynecology, Medical University of Pleven, Bulgaria. Paraffin embedded tumor tissues were immunohistochemically tested for the levels of expression of ROMO1. The results for both Allred score and H-score were investigated for association with tumor size, lymph node status and FIGO stage. RESULTS: Levels of ROMO1 were significantly higher in FIGO1 stage compared to FIGO2 and FIGO3 according to both scores (for H-score FIGO1 vs FIGO2 p = 0.00012; FIGO 1 vs FIGO3 p = 0.0008; for Allred score FIGO1 vs FIGO2, p = 0.0029; FIGO1 vs FIGO3 (p = 0.012). Statistically significant difference was found according to the H-score between patients with and without metastatic lymph nodes (p = 0.033). CONCLUSION: To the best of our knowledge this is the first study testing immunohistochemically the expression of ROMO1 for CC progression. The levels of ROMO1 were significantly higher in early stage tumors compared to advanced. Bearing in mind that only 75 patients were tested, further studies are required to evaluate the value of ROS in CC.

Surgical and Anatomical Basics of Pelvic Debulking Surgery for Advanced Ovarian Cancer - the "Hudson Procedure" as a Cornerstone of Complete Cytoreduction.

Ovarian cancer (OC) is the fifth most common cause of death in women and accounts for more deaths than any other cancer of the female reproductive tract. OC usually spreads through peritoneal dissemination and direct invasion. Optimal cytoreduction (no macroscopic residual disease) and adjuvant platinum-based chemotherapy are the fundaments of OC treatment. OC is usually diagnosed at advanced stages, hence the obliteration of the Douglas pouch by the tumor as well as disseminated pelvic peritoneal carcinomatosis are commonly seen. Radical surgical cytoreduction typically requires a retroperitoneal approach to the pelvic masses and multivisceral resections in the upper abdomen. In 1968, Christopher Hudson introduced a new retroperitoneal surgical technique ("radical oophorectomy") for fixed ovarian tumors. Since then, numerous modifications have been described, including visceral peritonectomy, the "cocoon" technique, Bat-shaped en-bloc total peritonectomy (Sarta-Bat approach), or en-bloc resection of the pelvis. Although these modifications expanded the classical description in many ways, the concepts and key surgical steps are derived from the Hudson procedure. However, there are some gaps or disagreements regarding the anatomical or practical rationale for certain surgical steps. The purpose of this article is to outline the critical steps of radical pelvic cytoreduction ("Hudson procedure"), and to delineate the anatomical basis for the procedure in the proposed form. In addition, we discuss the controversies and address the perioperative morbidity associated with the procedure.

Electronic brachytherapy for gynecological cancers - a systematic review.

Background: The purpose of this manuscript is to provide an in-depth literature review of the management of endometrial and cervical cancers with electronic brachytherapy. Materials and methods: An extensive literature search was performed and 9 articles were selected based on preset criteria. Results: The reviewed studies provided dosimetric and clinical results. Patient populations were diverse and prescribed doses varied. When treatment plans were compared to those using cobalt 60 (60Co) and iridium 192 (192Ir) sources researchers found lower or equivalent doses in organs at risk while the doses at the applicator surface were significantly higher for electronic brachytherapy. In the eligible studies, a total of 72 patients received treatment with AxxentXoft vaginal applicator, 29 were treated with the Intrabeam vaginal applicator, and 8 with AxxentXoft cervical applicator. Conclusions: All authors found that electronic brachytherapy was safe and well tolerated as higher mucosal doses did not present as adverse clinical effects. Electronic brachytherapy for gynecological cancers has the potential to achieve equivalent tumor control while minimizing bowel and urinary toxicity thus improving the quality of life. More clinical data is needed to stratify patients who would benefit the most.

Vascular Anatomy and Variations of the Anterior Abdominal Wall - Significance in Abdominal Surgery.

Detailed knowledge of the human anatomy is an integral part of every surgical procedure. The majority of surgery related complications are due to a failure to possess appropriate knowledge of human anatomy. However, surgeons pay less attention of the anatomy of the anterior abdominal wall. It is composed of nine abdominal layers, which are composed of fascias, muscles, nerves, and vessels. Many superficial and deep vessels and their anastomoses supply the anterior abdominal wall. Moreover, anatomical variations of these vessels are often presented. Intraoperative and postoperative complications associated with entry and closure of the anterior abdominal wall could compromise the best surgical procedure. Therefore, sound knowledge of the vascular anatomy of the anterior abdominal wall is fundamental and a prerequisite to having a favourable quality of patient care. The purpose of the present article is to describe and delineate the vascular anatomy and variations of the anterior abdominal wall and its application in abdominal surgery. Consequently, the most types of abdominal incisions and laparoscopic accesses will be discussed. Furthermore, the possibility of vessels injury related to different types of incisions and accesses will be outlined in detail. Morphological characteristics and distribution pattern of the vascular system of the anterior abdominal wall is illustrated by using figures either from open surgery, different types of imaging modalities or embalmed cadaveric dissections. Oblique skin incisions in the upper or lower abdomen such as McBurney, Chevron and Kocher are not the topic of the present article.

A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare cancer type with an increasing incidence worldwide. We aimed to develop a rational gene expression-based prognostic score in MPM using publicly available datasets. METHODS: We developed and validated a two-gene prognostic score (2-PS) using three independent publicly available gene expression datasets. The 2-PS was built using the Robust Likelihood-Based Survival Modeling with Microarray Data method. RESULTS: We narrowed down the model building to the analysis of 179 genes, which have been shown previously to be of importance to MPM development. Our statistical approach showed that a model including two genes (GOLT1B and MAD2L1) was the best predictor for overall survival (OS) (p < 0.0001). The binary score based on the median of the continuous score stratified the patients into low and high score groups and also showed statistical significance in uni- and multivariate models. The 2-PS was validated using two independent transcriptomic datasets. Furthermore, gene set enrichment analysis using training and validation datasets showed that high score patients had distinct gene expression profiles. Our 2-PS also showed a correlation with the estimated infiltration by some immune cell fractions such as CD8+ T cells and M1/2 macrophages. Finally, 2-PS correlated with sensitivity or resistance to some commonly used chemotherapeutic drugs. CONCLUSION: This is the first study to demonstrate good performance of only two-gene expression-based prognostic scores in MPM. Our initial approach for features selection allowed for an increased likelihood for the predictive value of the developed score, which we were also able to demonstrate.