Salvage surgery for patients with residual disease after chemoradiation therapy for locally advanced cervical cancer: A systematic review on indication, complications, and survival.

INTRODUCTION: Standard treatment for locally advanced cervical cancer is chemoradiation therapy. Treatment with chemoradiation therapy harbors a risk of local residual disease, which can be curatively treated with salvage surgery, but the risk of complications following surgical procedures in radiated tissue is not negligible. The presence of residual disease can be radiologically and/or histologically diagnosed. The objective of this study is to describe studies that report on salvage surgery for patients with locally advanced cervical cancer after primary treatment with chemoradiation therapy. Therefore, we assessed the method of determining the presence of residual disease, the risk of complications, and the survival rate after salvage surgery. MATERIAL AND METHODS: PubMed, EMBASE, and the Cochrane database were searched from inception up to 6 March 2020. Titles and abstracts were independently assessed by two researchers. Studies were eligible for inclusion when patients had locally advanced cervical cancer with radiologically suspected or histologically confirmed residual disease after chemoradiation therapy, diagnosed with a CT, MRI, or PET-CT scan, or biopsy. Information on complications after salvage surgery and survival outcomes had to be reported. Methodological quality of the articles was independently assessed by two researchers with the Newcastle-Ottawa scale. RESULTS: Of the 2963 screened articles, six studies were included, representing 220 women. A total of 175 patients were treated with salvage surgery, of whom 27%-100% had residual disease on the surgery specimen. Of the 161 patients treated with salvage surgery based on positive biopsy results, 72%-100% showed residual disease on the surgery specimen. Of the 44 patients treated with salvage surgery based on suspected residual disease on radiology, 27%-48% showed residual disease on the salvage surgery specimen. A total of 105 complications were registered in 175 patients treated with salvage surgery. The overall survival rate after salvage surgery was 69% (mean follow-up period of 24.9 months). CONCLUSIONS: It is necessary to confirm residual disease by biopsy before performing salvage surgery in patients with locally advanced cervical cancer primarily treated with chemoradiation therapy. Salvage surgery only based on radiologically suspected residual disease should be avoided to prevent unnecessary surgery and complications.

Cervical cancer with ≤5 mm depth of invasion and >7 mm horizontal spread - Is lymph node assessment only required in patients with LVSI?

OBJECTIVE: Cervical cancer with ≤5 mm depth of invasion and >7 mm horizontal spread is classified FIGO IA instead of FIGO IB in the revised staging system, as horizontal spread is no longer considered. We aimed to determine the incidence of lymph node metastasis (LNM) and, consequently, the necessity of pelvic lymph node assessment. METHODS: Patients diagnosed between January 2015 and May 2019 with cervical cancer FIGO (2009) stage IB with ≤5 mm depth of invasion and >7 mm horizontal spread, were identified from the Netherlands Cancer Registry. Associations between disease-characteristics and lymph node metastasis (LNM), and overall survival, were assessed. RESULTS: Of 170 patients, six (3.5%) had LNM: 4/53 (7.6%) with adenocarcinoma and 2/117 (1.7%) with squamous cell carcinoma (p = .077). Four-year overall survival was 98.2%. LNM was observed more often in tumours with LVSI (4/43 patients, 9.3%) than without LVSI (2/117 patients, 1.7%) (p = .045). In adenocarcinoma with 3-5 mm depth of invasion LNM rate was 10% (4/40). None of the following tumours were observed with LNM: squamous cell carcinoma without LVSI (0/74); adenocarcinoma with <3 mm depth of invasion (0/13); <3 mm depth of invasion without LVSI (0/36). CONCLUSIONS: Lymph node assessment is essential in any tumour with LVSI or in adenocarcinoma with 3-5 mm depth of invasion. It can be omitted in squamous cell carcinoma without LVSI, in adenocarcinoma with <3 mm depth of invasion and in any tumours without LVSI and with <3 mm depth of invasion.

Monitoring unfractionated heparin in pediatric patients with congenital heart disease having cardiac catheterization or cardiac surgery.

Determine the effect of age and congenital heart disease (CHD) on whole blood tests for monitoring unfractionated heparin (UFH) in children. Determine correlation with anti-Xa levels in children undergoing cardiac catheterization or cardiac surgery. A prospective cross-sectional study of 211 healthy children about to have minor surgery (median age 3.5 years) and 110 CHD patients (median age 2.1 years) undergoing cardiac catheterization or cardiac surgery. Commonly used whole blood tests (two activated clotting times and an activated partial thromboplastin time; ACT+, ACT-LR, and APTT, respectively) were obtained before procedures and after UFH in CHD patients. Data were analyzed for effect of age and CHD and correlation with anti-Xa levels. In healthy subjects the ACT+ was lower in younger (<3 years) patients while the ACT-LR and APTT were unaffected. CHD patients exhibited an opposite trend with higher values in the younger patients. After bolus heparin the ACT+ exhibited the strongest correlation (r = 0.89) with anti-Xa levels in both locations (the APTT was too sensitive at post-bolus levels). When anti-Xa levels were below 1.0 IU/ml (range of thromboembolism therapy 0.35-0.7 IU/ml), the APTT correlation coefficient was 0.72. Some whole blood coagulation tests are affected by age in healthy children similar to laboratory tests and are variably influenced by the presence of CHD. ACT+ is the most reliable predictor of anti-Xa levels in both catheterization and surgery for pediatric patients. The APTT exhibited stronger correlation with anti-Xa than previous reports of laboratory APTT and warrants further evaluation for monitoring heparin thromboembolism therapy.

A novel multiparametric flow cytometry-based cytotoxicity assay simultaneously immunophenotypes effector cells: comparisons to a 4 h 51Cr-release assay.

Natural killer (NK) cell-or T cell-mediated cytotoxicity traditionally is measured in 4-16 h (51)Cr-release assays (CRA). A new four-color flow cytometry-based cytotoxicity assay (FCC) was developed to simultaneously measure NK cell cytotoxicity and NK cell phenotype (CD3(-)CD16(+)CD56(+)). Target cells, K562 or Daudi, were labeled with Cell Tracker Orange (CTO) prior to the addition of effector cells. Following co-incubation, 7 amino-actinomycin D (7-AAD) was added to measure death of target cells. The phenotype of effectors, viability of targets, the formation of tumor-effector cell conjugates and absolute numbers of all cells were measured based on light scatter (FSC/SSC), double discrimination of the fluorescence peak integral and height, and fluorescence intensity. Kinetic studies (0.5 and 1 to 4 h) at different effector to target (E:T) cell ratios (50, 25, 12, and 6) confirmed that the 3 h incubation was optimal. The FCC assay is more sensitive than the CRA, has a coefficient of variation (CV) 8-13% and reliably measures NK cell-or lymphokine-activated killer (LAK) cell-mediated killing of target cells in normal controls and subjects with cancer. The FCC assay can be used to study a range of phenotypic attributes, in addition to lytic activity of various subsets of effector cells, without radioactive tracers and thus, it is relatively inexpensive. The FCC assay has a potential for providing information about molecular interactions underlying target cell lysis and thus becoming a major tool for studies of disease pathogenesis as well as development of novel immune therapies.

Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer.

Patients with squamous cell carcinoma of the head and neck (SCCHN) have depressed antitumour immunity. The presence of CD4+CD25+ (Treg) cells in these patients might be, in part, responsible for downregulation of antitumour immune responses. To evaluate the frequency and characteristics of Treg in the peripheral circulation of patients with SCCHN, we used multicolour flow cytometry. Expression of CCR7, CD62L, zeta chain and Annexin V binding to Treg and non-Treg CD4+ lymphocyte populations were evaluated. Treg were confirmed to be Foxp3+ and GITR+. The Treg frequency was significantly elevated in patients with active disease and those with no evidence of disease (NED) following curative therapies. Both Treg and non-Treg CD4+ T cells in patients were significantly enriched in CCR7- and CD62L- cell subsets. Although Treg in patients contained a higher proportion of double negative (CCR7-CD62L-) cells, the majority of Tregs were CCR7-CD62L+. The proportion of Annexin V+CD4+ T cells was higher in patients (P<0.00005) than normal controls (NC), and Treg were significantly more sensitive to apoptosis than non-Treg in patients and NC. Expression of zeta was reduced in all subsets of CD4+ T cells obtained from patients vs NC. The data suggest that Treg in patients with SCCHN largely contain T cells with the 'effector' phenotype, which bind Annexin V and have low zeta expression, consistent with their activation state and a rapid turnover in the peripheral circulation.

[Thyroid status in anemic pregnant women under conditions of endemic goiter]. / Sostoianie shchitovidnoi zhelezy u beremennykh s anemiei v usloviiakh zobnoi éndemii.

Anemia is a highly prevalent condition among pregnant women in the Republic of Kazakhstan. The causes of this anemia are not quite clear, as is the problem of resistance of this type of anemia to therapy with iron preparations. The authors propose that this may be explained by the fact that many regions of the Republic are foci of endemic goiter, because tentative studies indicate a relationship between endemic goiter and hypothyrosis. The present study was aimed at examination of the thyroid status in pregnant women suffering from anemia in the town of Alma-Ata, a region endemic for goiter. Altogether 120 anemic pregnant women were examined, 60 of these with goiter and 60 without it. Control group consisted of 20 healthy pregnant women. Clinical and ultrasonic examinations, puncture biopsy of the thyroid, measurements of blood levels of TTH, total and free triiodothyronine and thyroxin, thyroxin-binding globulin, as well as of peripheral blood red cell counts, levels of hemoglobin, serum iron, assessment of total iron-binding capacity of the serum and saturation coefficient, were carried out. Healthy pregnant women from a focus of endemic goiter were found to represent a group at risk of anemia in the third pregnancy trimester. In anemic pregnant women endemic goiter aggravated anemia. Chronic iodine deficiency is conductive to formation in pregnant women of subclinical hypothyrosis whose severity increased in the presence of anemia, more so if anemia is paralleled by goiter.

[Features of adaptation of newborns born to mothers with endemic goiter]. / Osobennosti adaptatsii novorozhdennykh, rodivshikhsia u materei s éndemicheskim zobom.

Relationships between chronic iodine deficiency and, among other things, endemic goiter in women and adaptation of their babies in the early neonatal period were studied. A total of 125 women with endemic goiter of the Ist-IInd degrees and their newborns were examined. The diagnosis of endemic goiter was verified by the findings of an objective examination, ultrasonic examination, and puncture biopsy of the thyroid. Blood levels of triiodothyronine and thyroxin were measured in the women on days 3-4 postpartum. In the newborns Apgar score, body mass and length at birth, degree of maturity, physiologic body mass loss, duration of the icteric syndrome, time of umbilical cord drop off, and immunity status from the data of NBT test were assessed. Forty-five women without goiter and their newborns were controls. Postpartum measurements of triiodothyronine and thyroxin levels in the blood of patients with endemic goiter brought the authors to a conclusion that subclinical hypothyrosis was characteristic of them. Adaptation processes in the early neonatal period were found disordered in the newborns of mothers with endemic goiter. This manifested by a higher, vs. controls, incidence of asphyxia, hypotrophy, signs of the CNS involvement, and respiratory distress syndrome. Initial body mass recovery, disappearance of the icteric syndrome, umbilical cord loss were delayed in these newborns in comparison with the controls, and statistically reliable deviations in their immune status were revealed.