Postoperative outcomes of primary and interval cytoreductive surgery for advanced ovarian cancer registered in the Dutch Gynecological Oncology Audit (DGOA).

OBJECTIVES: The challenge when performing cytoreductive surgery (CRS) is to balance the benefits and risks. The aim of this study was to report short term postoperative morbidity and mortality in relation to surgical outcome in patients undergoing primary debulking surgery (PDS) or interval debulking (IDS) surgery in the Netherlands. METHODS: The Dutch Gynecological Oncology Audit (DGOA) was used for retrospective analysis. Patients undergoing PDS or IDS between January 1st, 2015 - December 31st, 2018 were included. Outcome was frequency of postoperative complications. Median time to adjuvant chemotherapy and severity of complications were related to outcome of CRS. Complications with Clavien-Dindo ≥3 were analyzed per region and case mix corrected. Statistical analysis was performed with R.Studio. RESULTS: 1027 patients with PDS and 1355 patients with IDS were included. Complications with re-invention were significantly higher in PDS compared to IDS (5.7% vs. 3.6%, p = 0.048). Complete cytoreduction was 69.7% in PDS and 62.1% IDS, p < 0.001. Time to adjuvant chemotherapy was 49 days in patients with complete CRS and a complication with re-intervention. Regional variation for severe complications showed one region outside confidence intervals. CONCLUSIONS: Higher complete cytoreduction rate in the PDS group indicates that the correct patients have been selected, but is associated with a higher percentage of complication with re-intervention. As result, time to start adjuvant chemotherapy is longer in this group. Maintaining a balance in aggressiveness of surgery and outcome of the surgical procedure with respect to severe complications is underlined. Bench marked data should be discussed nationally to improve this balance.

No influence of sarcopenia on survival of ovarian cancer patients in a prospective validation study.

OBJECTIVE: Decrease in skeletal muscle index (SMI) during neoadjuvant chemotherapy (NACT) has been associated with worse outcome in patients with advanced ovarian cancer. To validate these findings, we tested if a decrease in SMI was a prognostic factor for a homogenous cohort of patients who received NACT in the randomized phase 3 OVHIPEC-trial. METHODS: CT-scans were performed at baseline and after two cycles of neoadjuvant chemotherapy in stage III ovarian cancer patients. The SMI (skeletal muscle area in cm2 divided by body surface area in m2) was calculated using SliceOMatic software. The difference in SMI between both CT-scans (ΔSMI) was calculated. Cox-regression analyses were performed to analyze the independent effect of a difference in SMI (ΔSMI) on outcome. Log-rank tests were performed to plot recurrence-free (RFS) and overall survival (OS). The mean number of adverse events per patient were compared between groups using t-tests. RESULTS: Paired CT-scans were available for 212 out of 245 patients (87%). Thirty-four of 74 patients (58%) in the group with a decrease in ΔSMI and 73 of 138 of the patients (53%) in the group with stable/increase in ΔSMI had died. Median RFS and OS did not differ significantly (p = 0.297 and p = 0.764) between groups. Patients with a decrease in SMI experienced more pre-operative adverse events, and more grade 3-4 adverse events. CONCLUSION: Decreased SMI during neoadjuvant chemotherapy was not associated with worse outcome in patients with stage III ovarian cancer included in the OVHIPEC-trial. However, a strong association between decreasing SMI and adverse events was found.

Epidemiological role of birds in the transmission and maintenance of zoonoses. / Papel epidemiológico de las aves en la transmisión y mantenimiento de zoonosis.

The risk of zoonoses spreading from birds to humans is lower, quantitatively speaking, than the risk of transmission between other host groups, because the two taxonomic groups share fewer pathogens. Nevertheless, birds have a number of epidemiological characteristics that make them extremely important hosts in the transmission and maintenance of zoonoses, including their susceptibility to pathogens that are extremely hazardous to humans (such as highly pathogenic avian influenza virus, West Nile virus and Chlamydia psittaci) and their ability to travel long distances, especially in the case of migratory birds. The fact that the human diet includes poultry products (meat, eggs and their by-products) also means that most human cases of foodborne zoonoses are infections of avian origin. Lastly, close contact between humans and pet birds or urban birds leads to interactions of public health concern. This article sets out to describe the main factors that determine the role of birds in the epidemiology of zoonotic infections.

Le risque que les oiseaux transmettent des zoonoses à l'homme est moins élevé, au plan quantitatif, qu'entre hôtes d'autres catégories, car le nombre d'agents pathogènes affectant à la fois ces deux groupes taxonomiques est moindre. Cependant, certaines particularités épidémiologiques des oiseaux leur font jouer un rôle d'hôtes importants dans la persistance et la transmission de zoonoses : d'une part, leur sensibilité à des agents pathogènes dangereux pour l'homme (par exemple, le virus de l'influenza aviaire hautement pathogène, le virus de West Nile, Chlamydia psittaci) et, d'autre part, leur capacité à se déplacer sur de longues distances, notamment dans le cas des oiseaux migrateurs. En outre, les produits avicoles faisant partie des denrées alimentaires consommées par l'homme (viande de volaille, oeufs et produits dérivés), la majorité des cas de zoonoses d'origine alimentaire diagnostiqués chez l'homme sont d'origine aviaire. Enfin, les contacts étroits entre les humains et leurs oiseaux de compagnie ou avec des oiseaux des villes entraînent des interactions qui sont à prendre en compte en santé publique. Les auteurs décrivent les principales caractéristiques épidémiologiques des oiseaux jugées déterminantes par rapport aux infections zoonotiques.

El riesgo de transmisión de zoonosis de aves a humanos es menor, cuantitativamente hablando, que el que tiene lugar entre otros grupos de hospedadores, debido a que estos dos grupos taxonómicos comparten un menor número de agentes patógenos. No obstante, algunas particularidades epidemiológicas de las aves las convierten en hospedadores de gran importancia en el mantenimiento y la transmisión de zoonosis, como su capacidad de contraer infecciones por agentes patógenos peligrosos para los humanos (como el virus de la influenza aviar altamente patógena, el virus del Nilo Occidental o Chlamydia psittaci, entre otros) así como su gran capacidad de desplazamiento, especialmente en el caso de las aves migratorias. Además, el hecho de que la alimentación humana incluya productos avícolas (carne y huevos y productos derivados) hace que la mayoría de casos de zoonosis de origen alimentario diagnosticados en humanos sean infecciones de origen aviar. Por último, el estrecho contacto entre humanos y mascotas aviares o aves urbanas conlleva interacciones de interés para la salud pública. Este trabajo pretende describir los principales determinantes epidemiológicos de las aves en relación con las infecciones zoonósicas.

Sensitivity of two methods to detect Mycoplasma agalactiae in goat milk.

BACKGROUND: Laboratory diagnostic techniques able to detect Mycoplasma agalactiae are essential in contagious agalactia in dairy goats. This study was designed: 1) to determine the detection limits of PCR and culture in goat milk samples, 2) to examine the effects of experimental conditions including the DNA extraction method, PCR technique and storage conditions (fresh versus frozen stored milk samples) on these methods and 3), to establish agreement between PCR and culture techniques using milk samples from goats with mastitis in commercial dairy herds. The study was conducted both on artificially inoculated and field samples. RESULTS: Our findings indicate that culture is able to detect M. agalactiae in goat milk at lower concentrations than PCR. Qualitative detection of M.agalactiae by culture and PCR was not affected by sample freezing, though the DNA extraction method used significantly affected the results of the different PCR protocols. When clinical samples were used, both techniques showed good agreement. CONCLUSIONS: The results from this study indicate that both culture and PCR are able to detect M. agalactiae in clinical goat mastitis samples. However, in bulk tank milk samples with presumably lower M. agalactiae concentrations, culture is recommended within the first 24 h of sample collection due to its lower limit of detection. To improve the diagnostic sensitivity of PCR in milk samples, there is a need to increase the efficiency of extracting DNA from milk samples using protocols including a previous step of enzymatic digestion.

[Treatment evaluation and clinical decision making using HKT-30-ROM]. / Behandelevaluatie en klinische besluitvorming met HKT-30-ROM.

BACKGROUND: By means of repeated, well-supported measurements of clinical dynamic indicators from the Historical, Clinical and Future - 30 (HKT-30) it is possible to monitor behavioural changes on the basis of risks and needs. The addition of extra score parameters allows us to distinguish client-specific risks and needs. In treatment evaluation it is important to visualise changes in these indicators of treatment evaluation because they are the key to the clinical decision-making process that determines further treatment and rehabilitation. AIM: To investigate whether HKT-30 indicators can be used to measure and visualise behavioral changes for the purpose of treatment evaluation. METHOD: A case study is used to illustrate how clinicians at the Forensic Psychiatric Clinic (FPK), De Woenselse Poort, ascertain risks, needs and changes and clarify these factors for the purpose of treatment evaluation and clinical decision-making. RESULTS: Routine treatment evaluation aided by visualised clinical HKT-30 indicators give the treatment team and the client a clearer picture of the behavioral changes for which the forensic treatment was prescribed. This evaluation provides significant starting-points for clinical decision making. CONCLUSION: Routine treatment evaluation along with a suitably adjusted HKT-30 make behavioural changes visible, render clinical decisions more transparent and provide valuable starting-points for a dialogue with the client about his treatment.

Hepatosplenic T-cell lymphoma presented with massive splenomegaly and pancytopenia - a case report.

BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma. Patients usually present with splenomegaly and pancytopenia but without lymphadenopathy. Immunohistochemistry (IHC) staining of bone marrow biopsy shows intra-sinusoidal infiltration of CD3 and CD56 T-lymphocytes. Current treatment strategy of HSTCL includes a CHOP regimen (cyclophosphamide, adriamycine, vincristine, prednisone) followed by autologous transplantation. CASE: A 28-year-old male presented with abdominal fullness, weight loss, and massive splenomegaly. Laboratory findings revealed pancytopenia. A CT scan of the abdomen displayed hepatomegaly and massive splenomegaly. The bone marrow pathology examination showed monotonous medium-sized lymphocytes with some cluster of atypical lymphocytes with loosely condensed chromatin and pale cytoplasm. The intra-sinusoidal location was more prominent after using IHC staining of CD3 and CD56, which are characteristics of HSTCL. We administered CHOP-based regiment every 3 weeks for 3 cycles; however, the response was a stable disease. Since the splenomegaly was still massive and compromised the patient, the multidisciplinary team decided to perform splenectomy. Unfortunately, the patient did not survive the surgery. CONCLUSION: Hepatosplenic T-cell lymphoma is a rare aggressive disease, which is part of peripheral T-cell lymphoma. CHOP-based chemotherapy appeared to be ineffective, and we need further studies to find the optimal treatment of HSTCL.

An overview of Clinical Quality Registries (CQRs) on gynecological oncology worldwide.

INTRODUCTION: Clinical Quality Registries (CQRs) were initiated in order to compare clinical outcomes between hospitals or regions within a country. To get an overview of these CQRs worldwide the aim of this study was to identify these CQRs for gynecological oncology and to summarize their characteristics, processes and QI's and to establish whether it is feasible to make an international comparison in the future. METHODS: To identify CQRs in gynecological oncology a literature search in Pubmed was performed. All papers describing the use of a CQR were included. Administrative, epidemiological and cancer registries were excluded as these registries do not primarily serve to measure quality of care through QI's. The taskforce or contact person of the included CQR were asked to participate and share information on registered items, processes and indicators. RESULTS: Five nations agreed to collaborate: Australia, Denmark, Italy, the Netherlands and Sweden. Denmark, Netherlands and Sweden established a nationwide registry, collecting data on multiple tumor types, and various QI's. Australia and Italy included patients with ovarian cancer only. All nations had a different process to report feedback results to participating hospitals. CONCLUSION: CQRs serve the same purpose to improve quality of care but vary on different aspects. Although similarities are observed in the topics measured by the QI's, an international comparison was not feasible as numerators or denominators differ between registries. In order to compare on an international level it would be useful to harmonize these registries and to set an international standard to measure the quality of care with similar indicators.

Primary breast lymphoma - a case report.

BACKGROUND: Primary breast lymphoma is a rare disease and accounts for 0.4-0.5% of malignant breast neoplasms and 1.7-2.2% of extra-nodal lymphomas, with diffuse large B-cell lymphoma (DLBCL) as the most common histologic subtype. CASE: A 47-year-old female with beta thalassemia presented with a lump of the left breast, redness, pain, and swelling of her left breast. Physical examination showed tender, red, swollen left breast. Laboratory findings show mild anemia and normal level of lactate dehydrogenase 329 U/L (normal range: 240-480 U/L). PET scan showed hypermetabolic mass with irregular margins covering the whole left breast quadrants with the size of 11.25 x 5.17cm with left pectoralis major, left parasternal, and left axillary hypermetabolic nodules. Histopathology and immunohistochemistry staining showed a non-germinal center B-cell-like subtype of DLBCL CD20+. We administered the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednison) every 3 weeks for 6 cycles. The response was complete remission. The patient tolerated the chemotherapy well and achieved long term complete remission. CONCLUSION: Primary breast lymphoma is a rare disease with the most common subtype is diffuse large B-cell lymphoma. Systemic chemother-apy R-CHOP is the treatment option for primary breast diffuse large B-cell lymphoma.

Clinical auditing as an instrument to improve care for patients with ovarian cancer: The Dutch Gynecological Oncology Audit (DGOA).

INTRODUCTION: The Dutch Gynecological Oncology Audit (DGOA) was initiated in 2014 to serve as a nationwide audit, which registers the four most prevalent gynecological malignancies. This study presents the first results of clinical auditing for ovarian cancer in the Netherlands. METHODS: The Dutch Gynecological Oncology Audit is facilitated by the Dutch Institute of Clinical Auditing (DICA) and run by a scientific committee. Items are collected through a web-based registration based on a set of predefined quality indicators. Results of quality indicators are shown, and benchmarked information is given back to the user. Data verification was done in 2016. RESULTS: Between January 01, 2014 and December 31, 2018, 6535 patients with ovarian cancer were registered. The case ascertainment was 98.3% in 2016. The number of patients with ovarian cancer who start therapy within 28 days decreased over time from 68.7% in 2014 to 62.7% in 2018 (p < 0.001). The percentage of patients with primary cytoreductive surgery decreased over time (57.8%-39.7%, P < 0.001). However, patients with complete primary cytoreductive surgery improved over time (53.5%-69.1%, P < 0.001). Other quality indicators did not significantly change over time. CONCLUSION: The Dutch Gynecological Oncology Audit provides valuable data on the quality of care on patients with ovarian cancer in the Netherlands. Data show variation between hospitals with regard to pre-determined quality indicators. Results of 'best practices' will be shared with all participants of the clinical audit with the aim of improving quality of care nationwide.

Health-related quality of life after interval cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage III ovarian cancer.

INTRODUCTION: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (CRS) improves recurrence-free (RFS) and overall survival (OS) in patients with FIGO stage III ovarian cancer. We evaluated the effect of HIPEC on patient's health-related quality of life (HRQoL) in the OVHIPEC trial. MATERIALS AND METHODS: OVHIPEC was a multicentre, open-label, randomized phase III trial for patients with stage III ovarian cancer. Patients were randomly assigned (1:1) to receive interval CRS with or without HIPEC with cisplatin. HRQoL was assessed using the EORTC QLQ-C30, and the ovarian (QLQ-OV28) and colorectal cancer (QLQ-CR38) modules. HRQoL questionnaires were administered at baseline, after surgery, after end of treatment, and every three months thereafter. HRQoL was a secondary endpoint, with the prespecified focus on the QLQ-C30 summary score and symptom scores on fatigue, neuropathy and gastro-intestinal symptoms. HRQoL was analysed using linear and non-linear mixed effect models. RESULTS: In total, 245 patients were randomized. One-hundred-ninety-seven patients (80%) completed at least one questionnaire. No significant difference over time in the QLQ-C30 summary scores was observed between the study arms (p-values for linear and non-linear growth: p > 0.133). The pattern over time for fatigue, neuropathy and gastro-intestinal symptoms did not significantly differ between treatment arms. CONCLUSION: The addition of HIPEC to interval CRS does not negatively impact HRQoL in patients with stage III ovarian cancer who are treated with interval CRS due to the extent of disease. These HRQoL results, together with the improvement in RFS and OS, support the viability of HIPEC as an important treatment option in this patient population. CLINICALTRIALS. GOV NUMBER: NCT00426257. EUDRACT NUMBER: 2006-003466-34.

Modulation of the major histocompatibility complex class II-associated peptide repertoire by human histocompatibility leukocyte antigen (HLA)-DO.

Antigen presentation by major histocompatibility complex class II molecules is essential for antibody production and T cell activation. For most class II alleles, peptide binding depends on the catalytic action of human histocompatibility leukocyte antigens (HLA)-DM. HLA-DO is selectively expressed in B cells and impedes the activity of DM, yet its physiological role remains unclear. Cell surface iodination assays and mass spectrometry of major histocompatibility complex class II-eluted peptides show that DO affects the antigenic peptide repertoire of class II. DO generates both quantitative and qualitative differences, and inhibits presentation of large-sized peptides. DO function was investigated under various pH conditions in in vitro peptide exchange assays and in antigen presentation assays using DO(-) and DO(+) transfectant cell lines as antigen-presenting cells, in which effective acidification of the endocytic pathway was prevented with bafilomycin A(1), an inhibitor of vacuolar ATPases. DO effectively inhibits antigen presentation of peptides that are loaded onto class II in endosomal compartments that are not very acidic. Thus, DO appears to be a unique, cell type-specific modulator mastering the class II-mediated immune response induced by B cells. DO may serve to increase the threshold for nonspecific B cell activation, restricting class II-peptide binding to late endosomal compartments, thereby affecting the peptide repertoire.

Activated complement is more extensively present in diseased aortic valves than naturally occurring complement inhibitors: a sign of ongoing inflammation.

BACKGROUND: Recent studies indicate a role for complement in the pathogenesis of aortic valve disease. However, the role of naturally occurring anti-complement mediators in this context is unknown. In this study, we have analysed this in three different pathological conditions of the aortic valve: degeneration, atherosclerosis and bacterial endocarditis. MATERIALS AND METHODS: Human aortic valves were obtained at autopsy (n = 30): 5 control valves, 10 aortic valves with atherosclerotic changes, 10 aortic valves with degenerative changes and 5 degenerative changed aortic valves with bacterial infection. These valves were analysed immunohistochemically for the presence of activated complement (C3d and C5b9) and the complement inhibitors C1-inh and clusterin. Areas of positivity were then quantified. RESULTS: C3d, C5b9 and the complement inhibitors C1-inh and clusterin depositions were mainly found in the endothelium and extracellular matrix in aortic valves. All these mediators were already present in control valves, but the area of positivity increased significantly in response to the different diseases, with the highest increase in response to bacterial endocarditis. Interestingly, in all three aortic diseases, the depositions of complement were significantly more widespread than that of their inhibitors. CONCLUSIONS: Our study indicates that anti-complement mediators (C1-inh and clusterin) are deposited in diseased aortic valves together with activated complement, indicating an existing counter response against complement locally in the valve. However, deposition of activated complement is significantly more widespread than that of its inhibitors, which could explain ongoing inflammation in those diseased aortic valves.

Understanding acute metabolic decompensation in propionic and methylmalonic acidemias: a deep metabolic phenotyping approach.

BACKGROUND: Pathophysiology of life-threatening acute metabolic decompensations (AMD) in propionic acidemia (PA) and isolated methylmalonic acidemia (MMA) is insufficiently understood. Here, we study the metabolomes of PA and MMA patients over time, to improve insight in which biochemical processes are at play during AMD. METHODS: Longitudinal data from clinical chemistry analyses and metabolic assays over the life-course of 11 PA and 13 MMA patients were studied retrospectively. Direct-infusion high-resolution mass spectrometry was performed on 234 and 154 remnant dried blood spot and plasma samples of PA and MMA patients, respectively. In addition, a systematic literature search was performed on reported biomarkers. All results were integrated in an assessment of biochemical processes at play during AMD. RESULTS: We confirmed many of the metabolite alterations reported in literature, including increases of plasma valine and isoleucine during AMD in PA patients. We revealed that plasma leucine and phenylalanine, and urinary pyruvic acid were increased during AMD in PA patients. 3-hydroxyisovaleric acid correlated positively with plasma ammonia. We found that known diagnostic biomarkers were not significantly further increased, while intermediates of the branched-chain amino acid (BCAA) degradation pathway were significantly increased during AMD. CONCLUSIONS: We revealed that during AMD in PA and MMA, BCAA and BCAA intermediates accumulate, while known diagnostic biomarkers remain essentially unaltered. This implies that these acidic BCAA intermediates are responsible for metabolic acidosis. Based on this, we suggest to measure plasma 3-hydroxyisovaleric acid and urinary ketones or 3-hydroxybutyric acid for the biochemical follow-up of a patient's metabolic stability.

The distribution and redistribution of carfentanil in post mortem samples.

This article compares 290 post mortem case reports that were positive for carfentanil. All the cases were submitted to, and analyzed by, the toxicology department of the Office of the Chief Medical Examiner, Edmonton, Alberta, Canada. This study highlights the varied distribution of carfentanil in the body after death as a result of misadventure, i.e., these are accidental drug overdose cases. Post mortem samples were collected from more than one anatomical site and analysed for carfentanil using a validated liquid chromatography-tandem mass spectrometry method. Ante-mortem samples were available in 15 of these cases and were also analysed. Post mortem mean blood carfentanil concentrations were found to be 0.362 µg/L (femoral), 0.442 µg/L (iliac), 0.484 µg/L (cardiac) and 0.692 µg/L (subclavian). The mean vitreous humor carfentanil concentration was 0.238 µg/L; the mean urine carfentanil concentration was found to be 0.697 µg/L. Little difference was found between ligated and 'blindstick' femoral blood carfentanil concentrations. Whilst carfentanil can readily be detected in both vitreous humor and urine samples neither were found to correlate with blood concentrations, limiting their use in interpretation. This study demonstrates the importance of multi-site sample collection and subsequent analysis for a thorough post mortem toxicological investigation. The study also highlights the risks and limitations associated with the interpretation of post mortem analytical results concerning carfentanil.

CO2 chemosensing in rat oesophagus.

BACKGROUND: Acid in the oesophageal lumen is often sensed as heartburn. It was hypothesised that luminal CO(2), a permeant gas, rather than H(+), permeates through the epithelium, and is converted to H(+), producing an afferent neural signal by activating chemosensors. METHODS: The rat lower oesophageal mucosa was superfused with pH 7.0 buffer, and pH 1.0 or pH 6.4 high CO(2) (P(CO2) = 260 Torr) solutions with or without the cell-permeant carbonic anhydrase (CA) inhibitor methazolamide (MTZ, 1 mM), the cell-impermeant CA inhibitor benzolamide (BNZ, 0.1 mM), the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine (CPZ, 0.5 mM) or the acid-sensing ion channel (ASIC) inhibitor amiloride (0.1 mM). Interstitial pH (pH(int)) was measured with 5',6'-carboxyfluorescein (5 mg/kg intravenously) loaded into the interstitial space, and blood flow was measured with laser-Doppler. RESULTS: Perfusion of a high CO(2) solution induced hyperaemia without changing pH(int), mimicking the effect of pH 1.0 perfusion. Perfused MTZ, BNZ, CPZ and amiloride all inhibited CO(2)-induced hyperaemia. CA XIV was expressed in the prickle cells, with CA XII in the basal cells. TRPV1 was expressed in the stratum granulosum and in the muscularis mucosa, whereas all ASICs were expressed in the prickle cells, with ASIC3 additionally in the muscularis mucosa. CONCLUSIONS: The response to CO(2) perfusion suggests that CO(2) diffuses through the stratum epithelium, interacting with TRPV1 and ASICs in the epithelium or in the submucosa. Inhibition of the hyperaemic response to luminal CO(2) by CA, TRPV1 and ASIC inhibitors implicates CA and these chemosensors in transduction of the luminal acid signal. Transepithelial CO(2) permeation may explain how luminal H(+) equivalents can rapidly be transduced into hyperaemia, and the sensation of heartburn.

Comparison of GP5+/6+-PCR and SPF10-line blot assays for detection of high-risk human papillomavirus in samples from women with normal cytology results who develop grade 3 cervical intraepithelial neoplasia.

Using a case control approach, we performed a two-way comparison study between GP5+/6+-PCR and HPV SPF(10)-Line Blot 25 (SPF(10)) assays for detection of 14 types of high-risk human papillomavirus (hrHPV) in samples from women with normal cytology results who had or developed grade 3 cervical intraepithelial neoplasia (CIN 3). Samples were pooled from two cohorts, i.e., women participating in population-based screening and women attending a gynecological outpatient clinic. Cases (n = 45) were women with histologically confirmed CIN 3 diagnosed within a median follow-up time of 2.7 (range, 0.2 to 7.9) years. Control samples were from women (n = 264) who had developed CIN 1 lesions at maximum (median follow-up at 5.8 [range, 0 to 10] years). Identical numbers of cases tested positive for 1 or more of the 14 hrHPV types by both systems (40/45; McNemar; P = 1.0). Conversely, SPF(10) scored significantly more controls as hrHPV positive than did GP5+/6+-PCR (95/264 versus 29/264; McNemar; P < 0.001). Consequently, women with normal cytology results and an hrHPV GP5+/6+-PCR-positive test exhibited a risk of CIN 3 that was 4.5 times higher (odds ratio [OR], 65; 95% confidence interval [95%CI], 24 to 178) than that seen for women with an hrHPV-positive SPF(10) test (OR, 14; 95%CI, 5 to 38)). Similar results were obtained after analysis of both cohorts separately. Discrepancy analysis by viral load assessment for the most common discordant hrHPV types (HPV16, -18, and -52) showed that samples which were SPF(10) positive only for these types had viral loads significantly lower than those for samples that were positive by both assays (analysis of variance; P < or = 0.006). Our data indicate that GP5+/6+-PCR has a better clinical performance than SPF(10) for women who are diagnosed with CIN 3 after prior normal cytology results. The extra positivity scored by SPF(10) mainly involved infections characterized by low viral loads that do not result in CIN 3.

First case of vaginal radical trachelectomy in a pregnant patient.

Women who present with cervical carcinoma during pregnancy pose for us a clinical problem. In general, three treatment options exist: (i) radical hysterectomy with termination of pregnancy, (ii) a planned delay, or (iii) chemotherapy until lung maturation has occurred, both followed by a radical hysterectomy. Vaginal radical trachelectomy is an alternative approach to preserve the pregnancy. We report on a woman with a stage IBI cervical carcinoma, diagnosed at 16 weeks of gestation treated with vaginal radical trachelectomy. At a gestational age of 36 weeks, a cesarean section was performed, followed by radical hysterectomy. Follow-up of 9 months is uneventful for both the mother and the child. The vaginal radical trachelectomy is a new approach in the treatment of cervical carcinoma during pregnancy.

The distribution and redistribution of fentanyl & norfentanyl in post mortem samples.

This article compares 249 post mortem case reports that were positive for fentanyl/norfentanyl. All the cases were submitted to, and analyzed by, the toxicology department of the Office of the Chief Medical Examiner, Edmonton, Alberta, Canada. This study highlights the varied distribution of fentanyl in the body after death as a result of misadventure, i.e., these are accidental drug overdose cases as opposed to a study of analytical data resulting from fentanyl use/administration in a clinical environment and/or death as a result of suicide. Post mortem samples were collected from more than one anatomical site and analyzed for fentanyl and norfentanyl using liquid chromatography-tandem mass spectrometry. Ante-mortem samples were available in 4 of these cases and were also analyzed. Post mortem mean blood fentanyl concentrations were found to be 13.2ng/mL (femoral), 19.1ng/mL (iliac) and 42.0ng/mL (subclavian). For norfentanyl the mean concentrations were 4.6ng/mL (femoral), 4.6ng/mL (iliac) and 7.4ng/mL (subclavian). Mean vitreous fentanyl and norfentanyl concentrations were 10.8ng/mL and 3.5ng/mL respectively. Mean liver fentanyl and norfentanyl concentrations were found to be 185.5ng/g and 18.8ng/g respectively. This study demonstrates the importance of multi-site sample collection and subsequent analysis for a thorough post mortem toxicological investigation. The study also highlights the risks and limitations associated with the interpretation of post mortem analytical results concerning fentanyl.