Intraoperative motive for incomplete resection in primary retroperitoneal sarcoma.

INTRODUCTION: Surgical resection is the current standard of care for retroperitoneal sarcoma (RPS). Recent data suggests that up to 5% of patient have incomplete (R2) resection. The exact reason why patients scheduled for surgery with a curative intent to treat ended up with an R2 resection is largely unknown. AIM OF THE STUDY: To identify intraoperative findings responsible for incomplete (R2) resection in primary RPS. METHODS: All records of consecutive patients scheduled for a non-metastatic primary RPS surgery between 1995 and 2020 in a tertiary care sarcoma centre were retrospective analyzed. RESULTS: Among the 347 patients scheduled for surgery, 13 (3.7%) had an incomplete (R2) resection. The reasons for incomplete surgery were intraoperative finding of vascular involvement of great vessels in 5 patients, previously undetected peritoneal metastases in 5 patients, invasion of contralateral kidney/ureter in 2 patients and the need to preserve both kidneys in 1 patient because of his past medical history. Among these patients, 3 had a laparotomy without resection and 10 had a partial resection (i.e. debulking surgery). Severe postoperative complications occurred in 5 patients. The median length of stay in hospital was 19days. After a median follow-up of 12months, the median survival of patients after incomplete resection was 18months. The 1-y, 5-y and 8-y overall survival (OS) for these patients were 46%, 14%, and 7%, respectively. CONCLUSION: Incomplete (R2) resection for a primary RPS surgery is rare in specialized sarcoma center. The next steps should be to identify the preoperative criteria that lead to this accurate selection and to define the best practice in front of a peroperative discovery of an unresectable RPS. LEVEL OF EVIDENCE: III.

HLA expression and cancer--14th IHIWS immunohistochemistry quality control exercise exchange results.

An immunohistochemistry (IH) quality control exercise was conducted as part of the 14th International HLA (human leukocyte antigen) and Immunogenetics Workshop (IHIWS) HLA Expression and Cancer component. Six laboratories participated and the exercises involved performing IH using three monoclonal antibodies (HC-10, beta2m and SI00) on three sequential paraffin-embedded melanoma sections provided by one laboratory. High-resolution digital photographs of five IH-stained sections were also distributed for interpretation. While there was generally good agreement between laboratories, several differences in staining and interpretation of IH sections were identified and possible reasons given. Interpretation of the high-resolution digital photographs showed a high level of concordance between laboratories. It is suggested that further exercises are conducted as part of future collaborative activities in order to further characterise areas of variability between IH performance and interpretation of results.

Fourier transform infrared imaging as a method for detection of HLA class I expression in melanoma without the use of antibody.

Human leukocyte antigen (HLA) class I expression in melanoma is usually assessed using immunohistochemical staining. Here we report on the use of Fourier transform infrared (FTIR) hyperspectral imaging, a method widely used in two-dimensional analysis of chemical components, to study HLA class I expression in tissue. Two-dimensional cluster colour images derived from unsupervised hierarchical cluster analysis of FTIR hyperspectral data on melanoma sections were compared with consecutive sections that were immunohistochemically stained for class I expression. HLA-class-I-positive and -negative areas were differentiated by FTIR cluster images in all eight melanoma sections investigated without the need for antibody attachment. FTIR imaging enables the distinction of HLA-class-I-positive from class-I-negative areas in melanoma. This method is accurate, rapid and cost-effective.

De novo translocation (8;12) and frontofacionasal dysplasia in a newborn boy.

We describe a newborn boy one of triplets, whose karyotype was 46,XY, t(8;12)(q22;q21). Prenatal diagnosis of multiple craniofacial anomalies had been made. Following delivery, the patient was thought to exhibit findings consistent with a diagnosis of frontofacionasal dysostosis. We hypothesize that one of the break points of this translocation may involve a gene essential to craniofacial development.

Parvoviral infection associated with increased nuchal translucency: a case report.

An increased fetal nuchal translucency detected by first trimester ultrasound has been associated with an elevated risk of aneuploidy. The etiology of the increased nuchal translucency in fetuses with normal chromosomes is uncertain, but it has been associated with poor pregnancy outcome. We report a fetus with increased nuchal translucency and a normal karyotype, in which parvovirus was detected by polymerase chain reaction in the amniotic fluid. Although an ultrasound detected an increased nuchal fold thickness in the second trimester, the pregnancy was otherwise uncomplicated. Parvovirus should be considered as a possible etiology of increased nuchal translucency. The risks to a fetus with first trimester parvovirus infections diagnosed under these conditions are uncertain and require larger studies.

Prenatal diagnosis and clinical features of an individual with tetrasomy 18p and trisomy 18q mosaicism.

Prenatal diagnosis and clinical follow up of a patient with mosaicism for anomalies of chromosome 18 are reported. The fetus appeared on ultrasound to have multiple anomalies, including clubbed feet, abnormal hand positioning, edema of the scalp, cleft palate, and polyhydramnios. The karyotype on amniocytes was 47,XY,+i(18p). Postnatally, the peripheral blood karyotype was 46,XY,+i(18q), whereas the skin fibroblast karyotype was 47,XY,+i(18p). The infant had many features consistent with those previously described in cases of tetrasomy 18p and some that were consistent with trisomy 18q.

Alloresponses to HLA-DP detected in the primary MLR: correlation with a single amino acid difference.

The one-way mixed lymphocyte reaction (MLR-1) response was measured in both directions in 50 HLA-A, B, DR and DQ identical pairs and the role of DP studied in MLR stimulation. DR, DQ and DP typing was performed at the allele level by the polymerase chain reaction-sequence specific oligotyping (PCR-SSO) technique. The group consisted of 19 potential bone marrow transplant recipients and 34 matched unrelated donors. When more than one matched donor was available for a patient, donor/donor MLR-1 was also studied. DP identity was observed in 3 out of 50 pairs (6%), however due to homozygosity no incompatibility was present in the stimulating cells in 21 out of 100 cases (21%). There was a significant difference in the range of relative responses (RR) between zero DPB1 mismatches and one (p = 0.002) and two (p = 0.02) DPB1 mismatches: 52.4% of cases in the zero DPB1 mismatch group had RR < 1.0% compared with 31.6% and 27.3% in the one and two DPB1 mismatches. Stimulation by DPB1*0201 and 0301 gave the highest RR (12.9 +/- 22.5 and 17.5 +/- 17.0, respectively) while stimulation with DPB1*0401 and 0402 resulted in low levels of T cell response (1.3 +/- 8.2 and 0.6 +/- 11.5, respectively). When the responses were restricted to DPB1*0401 homozygotes to standardise for responder type similar results were obtained (DPB1*0201 v DPB1*0402 p = 0.008). The protein products of the DPB1*0201 and 0402 alleles differ by a single amino acid at position 69 (DPB1*0402--Lysine, DPB1*0201--glutamic acid). A further analysis was performed therefore scoring responders and stimulators as glutamic acid positive (E+) or negative (E-). There was a highly significant increase in the response to E+ stimulators compared with E- stimulators (p = 0.004). There was also a significant difference in the distribution of relative responses between the E+ stimulator group and the subgroups of E- responders/E- stimulators (p = 0.012) and E+ responders/E- stimulators (p = 0.009). However the amino acid difference at position 69 does not explain all responses due to DP in the MLR-1 as evidenced by the strong responses observed in cases where DPB1*0301 (lysine pos.) was the only difference on the stimulator cells. The results indicate that not all DP incompatibilities elicit a measurable T cell MLR response, but where a response does occur residue 69 in the first domain of DP appears to be pivotal. These results may have implications with respect to GVHD in bone marrow transplantation.

Immunosusceptibility genes in rheumatoid arthritis.

The polygenic predisposition to RA is conferred particularly by disease susceptibility sequences in the HVR3 of HLA DRB1 present in those subtypes of DR4 and DR1 that are associated with RA. The aim of this study was to examine predisposing interactions between genes encoding HLA and immunoglobulin molecules. Accordingly, we compared the genetic background of 114 Australian patients with RA with that of Australian controls of similar ethnic background. We identified HLA-A, B, and DR phenotypes serologically, HLA-DR, DQ alleles, and subtypes of DR4 by DNA typing, and Gm allogenotypes and immunoglobulin switch region polymorphisms by RFLP. For the subjects with RA, we confirmed previously reported observations that included an excess of females, 71%, a high frequency of HLA types DR4 or DR1 of 77% versus controls 47%, and a high frequency of the HVR3 susceptibility sequences of 76%, with 24% homozygous, and 52% heterozygous for the sequences. We observed other genetic correlations in RA that included increases in frequencies of DR4 in males, DR1 in females, the class I specificity HLA-B27 overall but more particularly in females, 24% in females, versus 5% of controls, HLA-DQB1*0302 (DQ8) in DR4*0401-positive patients, and the Gm allogenotype 1,2,3;23 +/- ; 5,10, 15% of patients versus 4% of controls. Examination of switch region genes gave no evidence of differences in the polymorphisms distributions. Thus, the major genetic risks for RA that are conferred by female gender and the HVR3 of HLA DRB1 are modulated by interactions between gender and HLA class I and class II alleles, and the Gm allogenotype.

Amniotic fluid surfactant-albumin ratio as a screening test for fetal lung maturity. Two years of clinical experience.

An automated amniotic fluid surfactant-albumin ratio (SAR) test was performed as a screening test for pregnancies requiring fetal pulmonary maturity testing. Of the 178 neonates delivered within 3 days of the testing, respiratory distress syndrome (RDS) developed in 21 (11.8%) and transient tachypnea of the newborn infant (TTN) in 11 (6.1%). A positive test was defined as one which predicted RDS or TTN. Sensitivity was interpreted as the proportion of neonates with RDS or TTN detected by SAR less than 70 mg/gm. Sensitivity was 90.7% with a specificity of 76.1%. The positive predictive value was 45.3%; the negative predictive value 97.4%. The interassay coefficient of variability was 3.5%. The SAR test has proven to be a rapid, precise laboratory tool. Our combined testing protocol uses the SAR as an initial screening test with the lecithin/sphingomyelin ratio used as backup if the SAR did not predict maturity (SAR < 70 mg/gm). This protocol has markedly lowered the use of lecithin/sphingomyelin ratios while maintaining necessary clinical accuracy.

Effect of maternal carbon dioxide inhalation on human fetal breathing movements in term and preterm labor.

Induced maternal hypercapnia is a potent stimulus to fetal breathing movements in nonlaboring pregnant women. To determine the effect of maternal CO2 administration on fetal breathing movements during spontaneous labor, 14 healthy pregnant volunteers at term and 34 in preterm labor were recruited. If fetal breathing movements were markedly decreased or absent, the subjects were administered a prepared gas mixture of 3% CO2 in air. In term labor and in true preterm labor, fetal breathing movements were markedly decreased and could not be induced by maternal hypercapnia. Among women with suspected preterm labor, initial absence of fetal breathing movements and failure to evoke this response by maternal hypercapnia predicted delivery within 48 hours with a sensitivity of 80% and specificity of 95.5%. Induced maternal hypercapnia fails to stimulate fetal breathing movements in true term and preterm labor and may assist in distinguishing between true and false preterm labor.

Duplex Doppler ultrasonographic evaluation of the fetal renal artery in normal and abnormal fetuses.

Using duplex Doppler ultrasonography in asymmetrically grown fetuses with decreased amniotic fluid, we found the renal artery waveform pattern was different from that in the normally grown fetus. Such an abnormal waveform may reflect an increase in vascular resistance within the renal bed in oligohydramnios and intrauterine growth retardation. This would suggest that local mechanisms are operational and may influence renal blood flow in the human fetus with intrauterine growth retardation.

Human umbilical artery flow velocity waveforms before and after regional anesthesia for cesarean section.

The umbilical artery waveform was assessed in 18 normal nonlaboring patients before and after full surgical epidural anesthesia for repeat cesarean section. Using range-gated pulsed Doppler ultrasound, we found that the waveform analysis of the umbilical artery close to its placental insertion did not change significantly. These results suggest that no deleterious effect on fetoplacental circulation occurs with this form of anesthesia as long as maternal blood pressure is normal.