Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience.

OBJECTIVE: Hysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. METHODS: A retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. RESULTS: 121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. CONCLUSION: Our study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

Enhanced recovery after surgery (ERAS®) society guidelines for gynecologic oncology: Addressing implementation challenges - 2023 update.

BACKGROUND: Despite evidence supporting its use, many Enhanced Recovery After Surgery (ERAS) recommendations remain poorly adhered to and barriers to ERAS implementation persist. In this second updated ERAS® Society guideline, a consensus for optimal perioperative care in gynecologic oncology surgery is presented, with a specific emphasis on implementation challenges. METHODS: Based on the gaps identified by clinician stakeholder groups, nine implementation challenge topics were prioritized for review. A database search of publications using Embase and PubMed was performed (2018-2023). Studies on each topic were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded by an international panel according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS implementation challenge topics are based on best available evidence. The level of evidence for each item is presented accordingly. CONCLUSIONS: The updated evidence base and recommendations for stakeholder derived ERAS implementation challenges in gynecologic oncology are presented by the ERAS® Society in this consensus review.

Long-term survival in a stage IV small cell carcinoma of the endometrium.

•Small cell carcinoma of the endometrium is a rare malignancy with poor survival.•A patient was diagnosed with stage IV small cell carcinoma of the endometrium.•She was treated with surgery, chemotherapy (cisplatin/etoposide) and radiotherapy.•She remains disease free 5 years after completion of her treatments.

Development of small particle speciation for nuclear forensics by soft X-ray scanning transmission spectromicroscopy.

Synchrotron radiation spectromicroscopy provides a combination of submicron spatial resolution and chemical sensitivity that is well-suited to analysis of heterogeneous nuclear materials. The chemical and physical characteristics determined by scanning transmission X-ray microscopy (STXM) are complementary to information obtained from standard radiochemical analysis methods. In addition, microscopic quantities of radioactive material can be characterized rapidly by STXM with minimal sample handling and intrusion, especially in the case of particulate materials. The STXM can accommodate a diverse range of samples including wet materials, complex mixtures, and small quantities of material contained in a larger matrix. In these cases, the inventory of species present in a sample is likely to carry information on its process history; STXM has the demonstrated capability to identify contaminants and sample matrices. Operating in the soft X-ray regime provides particular sensitivity to the chemical state of specimens containing low-Z materials, via the K-edges of light elements. Here, recent developments in forensics-themed spectromicroscopy, sample preparation, and data acquisition methods at the Molecular Environmental Science Beamline 11.0.2 of the Advanced Light Source are described. Results from several initial studies are presented, demonstrating the capability to identify the distribution of the species present in heterogeneous uranium-bearing materials. Future opportunities for STXM forensic studies and potential methodology development are discussed.

Quality-of-life implications of risk-reducing cancer surgery.

BACKGROUND: Modern advances in genetic sequencing techniques have allowed for increased availability of genetic testing for hereditary cancer syndromes. Consequently, more people are being identified as mutation carriers and becoming aware of their increased risk of malignancy. Testing is commonplace for many inheritable cancer syndromes, and with that comes the knowledge of being a gene carrier for some patients. With increased risk of malignancy, many guidelines recommend that gene carriers partake in risk reduction strategies, including risk-reducing surgery for some syndromes. This review explores the quality-of-life consequences of genetic testing and risk-reducing surgery. METHODS: A narrative review of PubMed/MEDLINE was performed, focusing on the health-related quality-of-life implications of surgery for hereditary breast and ovarian cancer, familial adenomatous polyposis and hereditary diffuse gastric cancer. RESULTS: Risk-reducing surgery almost uniformly decreases cancer anxiety and affects patients' quality of life. CONCLUSION: Although the overwhelming quality-of-life implications of surgery are neutral to positive, risk-reducing surgery is irreversible and can be associated with short- and long-term side-effects.

A novel objective chute score interacts with monensin to affect growth of receiving cattle.

Growth in cattle may be related to animal temperament via alterations in intake or feed conversion. However, temperament is ill-defined, and different temperament measures may relate differently to production traits or interact with dietary factors in their effects. To examine relationships between diet, temperament, growth, and health, 160 crossbred steers (262 ± 22 kg) were used in a 56-d RCBD experiment with a 2 × 2 × 2 factorial treatment structure with 5 pens/treatment. Steers were pen fed a corn silage-based diet with or without monensin (41.9 g/t DM), ad libitum. Temperament treatments (assigned on d -7) were exit velocity (EV; slow vs. fast) and objective chute score (OCS; low vs. high), a novel temperament measure, representing the CV of weights collected at 5 measures/s for 10 s while an animal's head was restrained in a chute. Both were measured on d -7, 0, 14, 28, 55, and 56. Subjective chute scores (SCS; visual estimates of animal activity obtained simultaneously with OCS measures) were measured on d -7 and d 56. Jugular blood samples from d 28 were analyzed for antibody response to leptospirosis vaccine and NEFA concentrations. No monensin × OCS × EV interactions were detected ( ≥ 0.11). There was a positive correlation between SCS and OCS ( < 0.01; = 0.57). Changes in OCS and EV across the duration of the study differed among treatments (treatment × day, < 0.10) and indicated that initial measures may be better proxies of growth than average measures. There were no interactions between EV and OCS ( ≥ 0.15) for any response variable and no interactions among treatments ( ≥ 0.31), nor main effects of temperament factors ( ≥ 0.12) for DMI (%BW). Monensin decreased DMI ( < 0.01) similarly across all levels of EV and OCS. Gains and G:F responses to monensin depended on OCS ( < 0.10) but not EV ( ≥ 0.80). Gain was reduced ( < 0.10) by monensin with low, but not high, OCS, and G:F was increased ( < 0.10) by monensin on high, but not low, OCS. Gain during the second 4 wk was lesser ( = 0.04) in fast, compared with slow, EV animals. Results provide novel indications that certain temperament measures can interact with dietary manipulation to influence animal performance.

Ovarian cancer in Manitoba: trends in incidence and survival, 1992-2011.

BACKGROUND: Because the International Cancer Benchmarking Partnership, in a study of diagnosis years between 1995 and 2007, showed lower-than-expected survival for Manitoba's ovarian cancer patients, we undertook an analysis to describe the features of ovarian cancer diagnosed in Manitoba during a 20-year period. We also determined the most recent trends in survival to see if the previous results were sustained. METHODS: In this retrospective cohort study, ovarian cancer cases diagnosed during 1992-2011 were extracted from the Manitoba Cancer Registry. The incidence of ovarian cancer was calculated for the overall group and for age, morphology, residence, treatment, and stage. Trends over time, with a particular focus on changes that might correlate with poor survival, were analyzed. The 1- and 3-year relative survival rates were also calculated. RESULTS: The incidence of ovarian cancer did not vary over time (p = 0.640), even when stratified by age or morphology groups. Use of adjuvant chemotherapy decreased (p = 0.005) and use of neoadjuvant chemotherapy increased over time (p = 0.002). Diagnoses of stage iv cancers declined over time (p < 0.020). Trends in incidence did not coincide with previously observed decreases in relative survival. CONCLUSIONS: A decline in diagnoses of stage iv ovarian cancer could be responsible for a recent increase in relative survival. However, sample size might have limited power in some analyses, and the previously reported decrease in relative survival might have been due to a random fluctuation in the data. Future efforts will focus on continued monitoring of the patterns of ovarian cancer presentation and outcomes in Manitoba.

Malignant transformation of mature cystic teratoma of the ovary: 30-year experience of a single tertiary care center.

OBJECTIVE: To review the authors' experience with this rare disease and describe their management modality and the outcome. MATERIAL AND METHODS: From January 1983 to December 2013, 13 patients with malignant transformation arising in ovarian MCT were treated at the Division of Gynecologic Oncology in the University of Manitoba. Demographic characteristics, symptoms, signs, stage, mode of therapy, and results of follow-up were reviewed retrospectively. RESULTS: Median age at diagnosis was 53 years (range 25-65). The most common presenting symptom was a palpable mass in nine cases. Squamous cell carcinoma (SCC) was found in 38% (five cases), adenocarcinoma in 15% (two cases), anaplastic carcinoma in 8% (one case), and papillary thyroid carcinoma in 38% (five cases). Eight cases were Stage I, two cases were Stage II, and three cases were Stage III. All patients underwent surgery. Five patients received adjuvant treatment with platinum-based chemotherapy + pelvic radiation. Four patients had recurrent disease (two SCC and two adenocarcinoma). Three patients died of disease after recurrence. The median follow up period of the entire patient population was 60 months, with a three-year overall survival of 76%. CONCLUSION: Malignant transformation of MCT is large ovarian tumors that mainly occur in patients in their fifth and sixth decades of life. They often present as incidental pathologic findings after surgery for MCT. SCC has traditionally been the most common pathology, however in the present series, the authors found that papillary thyroid carcinoma was equally common. Platinum-based chemotherapy with pelvic radiation in early stage (including Stage IA) and locally recurrent dis- ease should be offered. Advanced stages and mucinous adenocarcinoma represent a poorer prognosis despite adjuvant treatment. In patients with papillary thyroid carcinoma, conservative surveillance in early stage and adjuvant total thyroidectomy with radioactive iodine treatment in advanced stage disease appears to be an effective treatment.

Informal caregiving to older cancer patients: preliminary research outcomes and implications.

BACKGROUND: The population of the Western world is aging while cancer survival rates are rising. Older patients with cancer will increasingly be taken care of by informal family caregivers. The current study describes levels of psychological distress, social support and coping abilities reported by partners who are caregivers to older patients with cancer (60+ years), comparing them to a control group of spouses of similarly aged people not suffering from life-threatening illness. PATIENTS AND METHODS: Two hundred sixteen partners who are primary caregivers of cancer patients aged 60+ were compared with 76 partners of healthy people aged 60+ and never diagnosed with any terminal illness. Participants completed self-reporting measures on psychological distress, coping ability and social support. RESULTS: Caregivers to cancer patients reported high levels of distress, low levels of social support and low levels of coping abilities which are negatively correlated to distress. Increased patient age was found to accentuate these processes. CONCLUSION: Age and the progression of cancer as a chronic illness present the physician with the reality that focus of care should be on the dyad (patient and caregiver), with high priority given to partners who are informal caregivers.

Superior vena cava syndrome - changing etiology in the third millennium.

Superior vena cava syndrome (SVCS), is diagnosed following different degrees of central venous system obstruction, which traditionally was caused by infections, tumors or fibrosing mediastinitis. Recently the role of SVC thrombosis secondary to indwelling central venous devices or pacemaker leads as well as different hypercoagulable states have drawn much attention. In the current review we present a 58-year-old female patient who underwent recurrent pacemaker replacements due to recurrent infections. The patient was hospitalized with superior vena cava syndrome and multiple thrombi in the upper body circulation. Additionally the evaluation was conducted for thrombophilia, which revealed the presence of high titers of antiphospholipid antibodies, suggesting the concurrent diagnosis of the antiphospholipid syndrome (APS). This case reflects the changes in the etiology of SVCS, and the need for a comprehensive evaluation of patients, in the search for additional factors that may complicate a pacemaker insertion, such as the presence of antiphospholipid antibodies. We review the relevant literature and highlight the importance for an interdisciplinary approach in the treatment of SVCS nowadays.

A role for PKCtheta in outside-in alpha(IIb)beta3 signaling.

Fibrinogen binding to platelets triggers alpha(IIb)beta3-dependent outside-in signals that promote actin rearrangements and cell spreading. Studies with chemical inhibitors or activators have implicated protein kinase C (PKC) in alpha(IIb)beta3 function. However, the role of individual PKC isoforms is poorly understood. Biochemical and genetic approaches were used to determine whether PKCtheta is involved in alpha(IIb)beta3 signaling. PKCtheta was constitutively associated with alpha(IIb)beta3 in human and murine platelets. Fibrinogen binding to alpha(IIb)beta3 stimulated the association of PKCtheta with tyrosine kinases Btk and Syk, and tyrosine phosphorylation of PKCtheta, Btk and the actin regulator, Wiskott-Aldrich syndrome protein (WASP). Mouse platelets deficient in PKCtheta or Btk failed to spread on fibrinogen. Furthermore, PKCtheta was required for phosphorylation of WASP-interacting protein on Ser-488, an event that has been linked to WASP activation of the Arp2/3 complex and actin polymerization in lymphocytes. Neither PKCtheta nor Btk were required for agonist-induced inside-out signaling and fibrinogen binding to alpha(IIb)beta3. Thus, PKCtheta is a newly identified, essential member of a dynamic outside-in signaling complex that includes Btk and that couples alpha(IIb)beta3 to the actin cytoskeleton.

The frequency split method for helical cone-beam reconstruction.

A new approximate method for the utilization of redundant data in helical cone-beam CT is presented. It is based on the observation that the original WEDGE method provides excellent image quality if only little more than 180 degrees data are used for back-projection, and that significant low-frequency artifacts appear if a larger amount of redundant data are used. This degradation is compensated by the frequency split method: The low-frequency part of the image is reconstructed using little more than 180 degrees of data, while the high frequency part is reconstructed using all data. The resulting algorithm shows no cone-beam artifacts in a simulation of a 64-row scanner. It is further shown that the frequency split method hardly degrades the signal-to-noise ratio of the reconstructed images and that it behaves robustly in the presence of motion.

Distinct functions of Vav1 in JNK1 activation in Jurkat T cells versus non-haematopoietic cells.

Vav1, the 95-kDa protein encoded by the vav1 proto-oncogene, is expressed exclusively in haematopoietic cells, where it becomes phosphorylated on tyrosine residues in response to antigen receptor ligation. Vav1 was found to act as a Rac1-specific guanine nucleotide exchange factor and to activate c-Jun N-terminal kinase (JNK1) in vitro and in ectopic expression systems using non-haematopoietic cells. Here, we studied the role of Vav1 in JNK1 activation in T cells versus non-haematopoietic cells. Vav1 overexpression activated JNK1 in COS7 and 293T cells but not in Jurkat T lymphocytes. In contrast, constitutively activated Rac1 efficiently stimulated JNK1 in both cell types under the same conditions. Vav1 did function in T cells because it clearly stimulated the activity of a nuclear factor of activated T-cell reporter plasmid in the same cells. Moreover, Vav1 induction of JNK1 in T cells required coexpression with calcineurin. This cooperation was cell type specific because it was not observed in COS7 or 293T cells. In contrast, Vav1 did not cooperate with calcineurin to activate either extracellular signal-regulated kinase 2 or p38. These findings demonstrate that Vav1 alone is a poor activator of the JNK1 pathway in T cells and emphasize the importance of studying the physiological functions of Vav1 in haematopoietic cells.

Vav1/Rac-dependent actin cytoskeleton reorganization is required for lipid raft clustering in T cells.

Formation of the immunological synapse (IS) in T cells involves large scale molecular movements that are mediated, at least in part, by reorganization of the actin cytoskeleton. Various signaling proteins accumulate at the IS and are localized in specialized membrane microdomains, known as lipid rafts. We have shown previously that lipid rafts cluster and localize at the IS in antigen-stimulated T cells. Here, we provide evidence that lipid raft polarization to the IS depends on an intracellular pathway that involves Vav1, Rac, and actin cytoskeleton reorganization. Thus, lipid rafts did not translocate to the IS in Vav1-deficient (Vav1-/-) T cells upon antigen stimulation. Similarly, T cell receptor transgenic Jurkat T cells also failed to translocate lipid rafts to the IS when transfected with dominant negative Vav1 mutants. Raft polarization induced by membrane-bound cholera toxin cross-linking was also abolished in Jurkat T cells expressing dominant negative Vav1 or Rac mutants and in cells treated with inhibitors of actin polymerization. However, Vav overexpression that induced F-actin polymerization failed to induce lipid rafts clustering. Therefore, Vav is necessary, but not sufficient, to regulate lipid rafts clustering and polarization at the IS, suggesting that additional signals are required.