Adenocarcinoma of the Uterine Cervix and its Precursor Lesion

__Abstract__ More than 2000 years have elapsed since the first description of cervical cancer by Hippocrates. Aretaeus, an ancient Greek physician practicing in the first century before Christ, described uterine cancer as superficial and deep ulcers, which later infiltrate the uterus1 • In 1812 John Clarke described a peculiar degeneration of the cervix, which he called a cauliflower tumor because of it's appearance2• Charles Mansneld Clarke introduced the term carcinoma uteri in 1821 and Hooper identified the cauliflower as a carcinoma of the cervix in 18323. Initia lly there was no distinction between cervical and endometrial carcinoma. Adenoma malignum was used for highly differentiated glandular carcinomas, without distinction in origin. When it became clear that cervical cancer was a separate entity, different types of cervical cancer were described. In German literature Portiokarzinom (karzinom der ektocervix, squamous cell carcinoma origi nating from the portio vaginalis) and Zervixhohlenkarzinom (karzinom der endocervix, adenocarcinoma arizing from the cervical channei)H were dist inguished. Ruge and Veit 1881 and later the school of Schroeder different iated between a portio carcinoma, arising from the connective tissue oft he cervix or from columnar epithelial erosions and cervical carcinoma arising from de cervical glands or from the connective tissue. Treub in 1892 proposed another classification, based on the extension of the different tumor types. He described t he carcinoma of the cervix, also called cancroid or epithelioma as a cancer which originated from the squamous epithelium of the portio vaginalis and the 'Zervixcarcinoma' (cervical cancer) which originated from the cervical glands8 . Today, we speak of cervical carcinoma, without differentiating between portio and cervical cancer

Low-energy electron irradiation damage in few-monolayer pentacene films

Quantum Matter and Optic

Low preoperative skeletal muscle density is predictive for negative postoperative outcomes in older women with ovarian cancer

Objective. To determine the predictive value of lumbar skeletal muscle mass and density for postoperative outcomes in older women with advanced stage ovarian cancer.Methods. A multicenter, retrospective cohort study was performed in women >= 70 years old receiving surgery for primary, advanced stage ovarian cancer. Skeletal muscle mass and density were assessed in axial CT slices on level L3. Low skeletal muscle mass was defined as skeletal muscle index = 2).Conclusion. Low skeletal muscle density, as a proxy of muscle quality, is associated with poor postoperative outcomes in older patients with advanced stage ovarian cancer. These findings can contribute to postoperative risk assessment and clinical decision making. (C) 2021 The Author(s). Published by Elsevier Inc.Cervix cance

Effect of surgical volume on short-term outcomes of cytoreductive surgery for advanced-stage ovarian cancer:A population-based study from the Dutch Gynecological Oncology Audit

Objective: Despite lacking clinical data, the Dutch government is considering increasing the minimum annual surgical volume per center from twenty to fifty cytoreductive surgeries (CRS) for advanced-stage ovarian cancer (OC). This study aims to evaluate whether this increase is warranted. Methods: This population-based study included all CRS for FIGO-stage IIB-IVB OC registered in eighteen Dutch hospitals between 2019 and 2022. Short-term outcomes included result of CRS, length of stay, severe complications, 30-day mortality, time to adjuvant chemotherapy, and textbook outcome. Patients were stratified by annual volume: low-volume (nine hospitals, &lt;25), medium-volume (four hospitals, 29–37), and high-volume (five hospitals, 54–84). Descriptive statistics and multilevel logistic regressions were used to assess the (case-mix adjusted) associations of surgical volume and outcomes. Results: A total of 1646 interval CRS (iCRS) and 789 primary CRS (pCRS) were included. No associations were found between surgical volume and different outcomes in the iCRS cohort. In the pCRS cohort, high-volume was associated with increased complete CRS rates (aOR 1.9, 95%-CI 1.2–3.1, p = 0.010). Furthermore, high-volume was associated with increased severe complication rates (aOR 2.3, 1.1–4.6, 95%-CI 1.3–4.2, p = 0.022) and prolonged length of stay (aOR 2.3, 95%-CI 1.3–4.2, p = 0.005). 30-day mortality, time to adjuvant chemotherapy, and textbook outcome were not associated with surgical volume in the pCRS cohort. Subgroup analyses (FIGO-stage IIIC-IVB) showed similar results. Various case-mix factors significantly impacted outcomes, warranting case-mix adjustment. Conclusions: Our analyses do not support further centralization of iCRS for advanced-stage OC. High-volume was associated with higher complete pCRS, suggesting either a more accurate selection in these hospitals or a more aggressive approach. The higher completeness rates were at the expense of higher severe complications and prolonged admissions.</p

Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver.

Whole-sporozoite (WSp) malaria vaccines induce protective immune responses in animal malaria models and in humans. A recent clinical trial with a WSp vaccine comprising genetically attenuated parasites (GAP) which arrest growth early in the liver (PfSPZ-GA1), showed that GAPs can be safely administered to humans and immunogenicity is comparable to radiation-attenuated PfSPZ Vaccine. GAPs that arrest late in the liver stage (LA-GAP) have potential for increased potency as shown in rodent malaria models. Here we describe the generation of four putative P. falciparum LA-GAPs, generated by CRISPR/Cas9-mediated gene deletion. One out of four gene-deletion mutants produced sporozoites in sufficient numbers for further preclinical evaluation. This mutant, PfΔmei2, lacking the mei2-like RNA gene, showed late liver growth arrest in human liver-chimeric mice with human erythrocytes, absence of unwanted genetic alterations and sensitivity to antimalarial drugs. These features of PfΔmei2 make it a promising vaccine candidate, supporting further clinical evaluation. PfΔmei2 (GA2) has passed regulatory approval for safety and efficacy testing in humans based on the findings reported in this study

Evaluation of effectiveness of the PlasmaJet surgical device in the treatment of advanced stage ovarian cancer (PlaComOv-study): study protocol of a randomized controlled trial in the Netherlands

Background: The most important goal for survival benefit of advanced stage ovarian cancer is to surgically remove all visible tumour, because complete cytoreductive surgery (CCS) has been shown to be associated with prolonged survival. In a remarkable number of women, CCS is very challenging. Especially in women with many small metastases on the peritoneum and intestinal surface, conventional CCS with electrosurgery is not able to be “complete” in removing safely all visible tumour. In this randomized controlled trail (RCT) we investigate whether the use of the PlasmaJet Surgical Device increases the rate of CCS, and whether this indeed leads to a longer progression free and overall survival. The main research question is: does the use of the PlasmaJet Surgical Device in surgery for advanced stage ovarian cancer result in an increased number of complete cytoreductive surgeries when compared with conventional surgical techniques. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. Methods: The study design is a multicentre single-blinded superiority RCT in two university and nine non-university hospitals in The Netherlands. Three hundred and thirty women undergoing cytoreductive surgery for advanced stage ovarian carcinoma (FIGO Stage IIIB-IV) will be randomized into two arms: use of the PlasmaJet (intervention group) versus the use of standard surgical instruments combined with electrocoagulation (control group). The primary outcome is the rate of complete cytoreductive surgery in both groups. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. Quality of life will be evaluated using validated questionnaires at baseline, at 1 and 6 months after surgery and at 1, 2, 3 and 4 years after surgery Discussion: We hypothesize the additional value of the use of the PlasmaJet in CCS for advanced stage epithelial ovarian cancer. More knowledge about efficacy, side effects, recurrence rates, cost effectiveness and pathology findings after using the PlasmaJet Device is advocated. This RCT may aid in this void

Preoperative predictors for residual tumor after surgery in patients with ovarian carcinoma

Objectives: Suboptimal debulking (>1 cm residual tumor) results in poor survival rates for patients with an advanced stage of ovarian cancer. The purpose of this study was to develop a prediction model, based on simple preoperative parameters, for patients with an advanced stage of ovarian cancer who are at risk of suboptimal cytoreduction despite maximal surgical effort. Methods: Retrospective analysis of 187 consecutive patients with a suspected clinical diagnosis of advanced-stage ovarian cancer undergoing upfront debulking between January 1998 and December 2003. Preoperative parameters were Karnofsky performance status, ascites and serum concentrations of CA 125, hemoglobin, albumin, LDH and blood platelets. The main outcome parameter was residual tumor >1 cm. Univariate and multivariate logistic regression was employed for testing possible prediction models. A clinically applicable graphic model (nomogram) for this prediction was to be developed. Results: Serum concentrations of CA 125 and blood platelets in the group with residual tumor >1 cm were higher in comparison to the optimally cytoreduced group (p 1 cm based on serum levels of CA 125 and albumin was established. Conclusion: Postoperative residual tumor despite maximal surgical effort can be predicted by preoperative CA 125 and serum albumin levels. With a nomogram based on these two parameters, probability of postoperative residual tumor in each individual patient can be predicted. This proposed nomogram may be valuable in daily routine practice for counseling and to select treatment modality. Copyrigh

Chemically augmented malaria sporozoites display an altered immunogenic profile

Despite promising results in malaria-naïve individuals, whole sporozoite (SPZ) vaccine efficacy in malaria-endemic settings has been suboptimal. Vaccine hypo-responsiveness due to previous malaria exposure has been posited as responsible, indicating the need for SPZ vaccines of increased immunogenicity. To this end, we here demonstrate a proof-of-concept for altering SPZ immunogenicity, where supramolecular chemistry enables chemical augmentation of the parasite surface with a TLR7 agonist-based adjuvant (SPZ-SAS(CL307)). In vitro, SPZ-SAS(CL307) remained well recognized by immune cells and induced a 35-fold increase in the production of pro-inflammatory IL-6 (p + cells 11.1 ± 1.8 vs. 9.4 ± 1.5%, p + T cells (4.7 ± 4.3 vs. 1.8 ± 0.7%, p + T cells (3.6 ± 1.4 vs. 2.5 ± 0.9%, p Host-parasite interactio

Conservative Therapy in Microinvasive Adenocarcinoma of the Uterine Cervix is Justified An Analysis of 59 Cases and a Review of the Literature

ObjectiveThis study aimed to evaluate the treatment and follow-up in a large series of women with early cervical adenocarcinoma (AC), stages IA1 and IA2, and to perform an extensive review of the literature in an effort to ascertain whether conservative therapy is justified.MethodsRecords of 59 cases of microinvasive AC diagnosed between 1987 and 2006 in the Rotterdam district, the Netherlands, were retrieved. Clinical and pathological data were reviewed and analyzed. A mesh review of all relevant literature concerning stage IA1 and IA2 was performed.ResultsOf all patients, 33 had stage IA1 and 26 stage IA2 cervical AC. Also, 42 patients were treated conservatively (ie, conization or simple hysterectomy) and 17 patients were treated radically (ie, radical hysterectomy/trachelectomy with lymph node dissection). Recurrence occurred in 1 patient (1.7%) with stage IA1 disease (grade 1 adenocarcinoma, depth 1.4 mm, and width 3.8 mm, with lymph vascular space involvement [LVSI]) treated by vaginal hysterectomy. The mean follow-up was 79.9 months. From the literature, pooling all data from patients with stage IA1 and IA2 AC, the risk of recurrent disease was 1.5% after conservative therapy and 2.0% after radical therapy.ConclusionsExtensive treatment such as radical hysterectomy with pelvic lymph node dissection or trachelectomy does not prevent recurrent disease. Patients with microinvasive AC should be treated identically to patients with SCC. In stage IA1 and IA2 AC, we recommend conservative therapy (by conization). In cases with LVSI, an additional lymphadenectomy is advised. For patients with stage IA2 AC with LVSI, a trachelectomy/radical hysterectomy with lymph node dissection should be considered.</jats:sec